Nutritional composition for administration to an individual

专利摘要:
nutritional composition to promote gut microbiotic balance and health. The present invention relates to nutritional compositions comprising a fructooligosaccharide (fos) in an amount of 35 to 44% by weight; a polysaccharide other than a partially hydrolyzed guar guar gum such as, for example, an arabinogalactan, in an amount from 50% to 38% by weight, and inulin in an amount from 12% to 24% by weight. fos and polysaccharide may be present in a carcass weight ratio of 1: 1. more specifically, fos and inulin may be present in a weight ratio of about 7: 3. Also presented are methods of promoting gut microbiotic balance and health. The methods include administering an effective amount of the nutritional composition to patients in need thereof.
公开号:BR112012011294B1
申请号:R112012011294-5
申请日:2010-11-11
公开日:2018-03-20
发明作者:Zamzam, (Fariba) Roughead；Benyacoub Jalil；Roessle Claudia；Rae Mager Jennifer；Ann Swanson Julie；Alan Greenberg Norman；Richard Bolster Douglas；Lucia Garcia-Rodenas Clara；Rochat Florence
申请人:Nestec S.A.；
IPC主号:

专利说明:

(54) Title: NUTRITIONAL COMPOSITION FOR ADMINISTRATION TO AN INDIVIDUAL (73) Holder: NESTEC S.A., Swiss Company. Address: Avenue Nestle 55, CH-1800 Vevey, SWITZERLAND (CH) (72) Inventor: ZAMZAM (FARIBA) ROUGHEAD; JALIL BENYACOUB; CLAUDIA ROESSLE; JENNIFER RAE MAGER; JULIE ANN SWANSON; NORMAN ALAN GREENBERG; DOUGLAS RICHARD BOLSTER; CLARA LUCIA GARCIARODENAS; FLORENCE ROCHAT
Validity Term: 20 (twenty) years from 11/11/2010, subject to legal conditions
Issued on: 03/20/2018
Digitally signed by:
Júlio César Castelo Branco Reis Moreira
Patent Director
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Descriptive Report of the Invention Patent for NUTRITIONAL COMPOSITION FOR ADMINISTRATION TO AN INDIVIDUAL. REFERENCES TO RELATED PATENT APPLICATIONS
The present patent application claims priority to U.S. application serial number 61 / 260,495, filed on November 12, 2009, the entire content of which is expressly incorporated herein by reference.
BACKGROUND
The present invention relates to nutritional compositions comprising dietary fibers to promote the balance of intestinal microbiotics and health and to methods for improving the balance of intestinal microbiotics and health, which includes administering an effective amount of such composition.
It is well known that infection by pathogenic bacteria can be harmful to health. Examples of these bacteria include Clostridium perfringens, C. difficile, Salmonella and other enteropathogens.
In the past, infection with these harmful bacteria was allowed to continue until it had to be treated with antibiotics. Antibiotics have a good effect on harmful bacteria. However, they suffer from the problem that they also kill populations of non-harmful intestinal bacteria and help digest food and provide other additional health benefits. These bacterial populations are often referred to as friendly.
Gram-positive, non-mobility, anaerobic bacteria often branched (Bifidobacteria) are one of the main genera of bacteria that make up the gut microbiota, the bacteria that reside in the colon. Bifidobacteria aid digestion, are associated with a lower incidence of allergies and also prevent some forms of tumor growth. Other health benefits of Bifidobacteria include greater defense against pathogenic bacteria, stimulation of the immune system, and health benefits related to acid production
2/72 short-chain fatty (SCFAs), as well as less abdominal tenderness.
Prebiotics are non-digestible substances that can beneficially affect the host by selectively stimulating the growth of microbiota in the intestine. Fruit-Oligosaccharides (FOS) are compounds that promote the growth of Bifidobacteria and other beneficial intestinal microbiotics, and have been studied extensively as prebiotics. FOS are short chain polymers of simple carbohydrates that do not behave like simple sugars in the body. FOS occur naturally in chicory, bananas, garlic and certain other foods and, technically, consists of a soluble fiber. It has been shown that FOS selectively support the proliferation of intestinal probiotics, especially Bifidobacteria.
Oligofructose (DE) is obtained from inulin, which is extracted from chicory using hot water. This results in a product with:
-92% of inulin-type fruit (molecules with β-2,1 fructosyl-fructose glycosidic bonds);
Degree of Polymerization (SD) ranging from 2-60 (average of 1012); and ~ 6-10% free sugars (fructose, glucose and sucrose).
Further processing (partial enzymatic hydrolysis or separation procedures) can result in OF products. This can also increase purity by removing free sugars. All connections on these products are in the β-2.1 configuration.
Alternatively, FOS is produced synthetically, starting with a sucrose molecule. The fungal enzyme β-fructidase is used to add fructose units with β-2,1 bonds in a process called transfrutosylation. A limited number of other connections are also formed by this process. The DP range is usually 2-4, and they all start with a glucose residue.
The term inulin-type fruit (ITF) refers to all linear fruits that contain β-2,1 fructose-fructose glycosidic bonds.
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The product contains molecules with variable DP and glucose proportion; generally described by the mean SD, maximum SD, or SD range.
Some ITFs have glucose as a starting unit (GFtype), while others do not (glucose-type)
ITFs are not uniformly labeled in the literature, as there is no official standard. However, they can be categorized by DP:
Long Chain => 10 DP; and
Short Chain = <10 SD.
The nomenclature for ITFs is inconsistent in the literature. Some consider OF and FOS to be synonymous and they are defined as ITFs with DPmax <10. Others use FOS to describe short-chain (DP <10) ITFs that are synthesized from sucrose and have the chemical structure GFn and fructose units enzymatically joined. OF describes short chain molecules derived from inulin hydrolysis and can have either the GFn structure or the Fn structure.
The additive PREBIO1 ™, available from Nestlé SA, is a unique prebiotic blend of FOS in soluble fibers and inulin, designed to support complete colon health, in particular the health of the proximal and distal colon, to help maintain the integrity of the colon. colon and promote healthy gut microbiotas. Formulas containing the PREBIO1 ™ additive may also provide nutritional support for patients with gastrointestinal (Gl) impairment, such as chronic diarrhea / malnutrition, premature enteral feeding, transition from TPN, small bowel syndrome, chronic pancreatitis, bad absorption related to cancer treatment, HIV / AIDS, delayed gastric emptying, and cystic fibrosis.
This current description satisfies the needs of the nutritional support industry by providing a composition with greater tolerance and greater prebiotic benefits compared to the PREBIO1 ™ additive, thereby providing a new composition that promotes the balance of intestinal microbiotics and the health of individuals which is administered.
summary
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The present description now presents a new nutritional composition that includes the combination of a FOS, a polysaccharide and inulin in relative amounts sufficient to provide nutrition when administered to an individual in need thereof. The composition provides a nutritional supplement to the individual's needs, and can be administered orally. Enteral administration for patients in need of tube feeding is also possible.
The composition generally comprises FOS in an amount of about 38% to about 44% by weight. The polysaccharide is typically an arabinogalactan, such as a gum and, in one embodiment, acacia gum (AG), and is present in an amount of about 38% to about 44% by weight. Inulin is present in an amount of about 12% to about 24% by weight. AG is a highly branched molecule of high molecular weight that comprises units of galactose, arabinose, rhamnose, and glucuronic acid. It is slowly fermented compared to other soluble fibers, and increases SCFA production and therefore can benefit the distal colon. See Cherbut, et al., Acacia Gum is a Bifidogenic Dietary Fiber with High Digestive Tolerance in Healthy Humans, Microbial Ecology in Health and Disease, 15 (1): 43-50 (2003). * AG has a very high gastrointestinal tolerance, in which up to 70 g / day does not cause any major side effects. See, Id. Low doses of AG (3 g / day) have been shown to be prebiotic and support the growth of Bifidobacteria when combined with 3 g / day of FOS. See Rochat, et al., Method of Treating Irritable Bowel Syndrome, U.S. Patent No. 7,141,554. Animal studies suggest AG's ability to increase diarrhea symptoms, and experiments with humans have revealed effects on normalized bowel function. See Wapnir, et al., Gum Arabic Promotes Rat Jejunal Sodium and Water Absorption from Oral Rehydration Solutions in Two Models of Diarrhea, Gastroenterology, 112 (6): 1979-1985 (1997). See also Bliss, et al., Supplementation with Gum Arabic Fiber Increases Fecal Ntrogen Excretion and Lowers Serum Urea Nitrogen Concentrationin Chronic Renal Failure Patients Consuming a Low-protein
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Diet, Am. J. Clin. Nutr., 63 (3): 392-398 (1996). See also Cherbut, et al. In addition, it has been shown that 5 g of AG added to a meal reduces the glycemic response, and chronic consumption of 25 g / day has a lipid-lowering effect. See Ross, et al., A Study of the Effects of Dietary Gum Arabic in Humans, Am. J. Clin. Nutr., 37 (3): 368-375 (1983).
In one embodiment, the nutritional composition of the present description comprises FOS and arabinogalactan, each present in an amount of about 40% to about 42% by weight; and inulin present in an amount of about 16% to about 20% by weight.
In one embodiment, the nutritional composition of the present description comprises FOS and arabinogalactan, each present in an amount of about 41% by weight; and inulin present in an amount of about 18% by weight.
It is advantageous that FOS and arabinogalactan are present in a weight ratio of about 44:38 to about 35:50, or from about 42:40 to about 40:42, or about 1: 1. In addition, it is advantageous that FOS and inulin are present in a weight ratio of about 38:24 to about 44:12, or from about 40:20 to about 42:16, or about 7 : 3.
In an embodiment of the nutritional composition of the present description, the FOS is present in an amount between 1.5 and 5.5 g / l, or about 4.12 g / l, arabinogalactan such as, for example, AG, is present in an amount of 1.5-5.5 g / l, or about 4.12 g / l, and inulin is present in an amount of 0.5-2.5 g / l, or about 1.76 g / l. This composition may further comprise partially hydrolyzed guar gum (PHGG) in an amount of up to 10 g / l. For example, PHGG can be supplied in an amount of about 2 g / l to about 9 g / l. In one embodiment, PHGG can be present in an amount of 7 g / l. In another embodiment, PHGG can be present in an amount of 2.6 g / l. In another embodiment, PHGG is present in an amount of 5 g / l.
It should be noted that, although guar gum is, chemically speaking, a polysaccharide, and although a PHGG may still be, at least in a small part, a polysaccharide, the polysaccharide included in the currently claimed nutritional composition does not include to PHGG. Instead, PHGG can be added in addition to the polysaccharide in such a way that, for example, AG and PHGG are not added together to obtain the 38-50% polysaccharide. Instead, PHGG can be added to nutritional compositions in addition to 38-50% polysaccharide.
In yet another embodiment, the nutritional composition of the present description also comprises at least one insoluble fiber, such as a soy fiber, a pea outer fiber, or both. In one embodiment, at least one insoluble fiber is a combination of a soy fiber and an outer pea fiber. The ratio between the soluble fiber of the composition, that is, FOS, arabinogalactans such as AG, and inulin, and the insoluble fiber is comprised between 1.5: 1 and 1: 1.5, or between 1.25: 1 and 1 : 1.25, or about 1: 1. In one embodiment, each of the FOS and AG is present in an amount between 2.5 and 3.5 g / l, and inulin is present in an amount between 1.25 and 1.75 g / l, and each of the soy fiber and the outer fiber of the pea is in an amount between 3.25 and 4.25 g / l. In yet another modality, FOS and AG are present in an amount of about 3 g / l, inulin is present in an amount of about 1.5 g / l, and each one among the soy fiber and the outer fiber of the pea is present in an amount of about 3.75 g / l.
Another embodiment of the present description relates to a dry powder formulation which comprises one of the nutritional compositions described herein. These powder compositions can be obtained by a method that includes preparing one of the nutritional compositions presented herein as a liquid and then drying the liquid through spray drying, freeze drying or other drying techniques. It is also contemplated the addition of additional nutritional components or compositions to the liquid before drying to provide increased nutritional benefits to the powder composition.
This description also refers to a number of methods
7/72 different treatments that are designed to provide nutrition to various individuals. In general, treatment methods promote the balance and health of intestinal microbiotics by administering an effective amount of the nutritional composition of the present description to an individual in need of such treatment.
Another method concerns increasing the patient's tolerance for various medical treatments that lead to disorders of the gastrointestinal tract, and such treatments include radiotherapy, chemotherapy, gastrointestinal surgery, anesthesia, administration of antibiotics, analgesic drugs or treatments for diarrhea. The method includes administering to such patients an effective amount of one of the nutritional compositions presented herein.
Another method refers to the provision of systemic benefits, such as better growth resumed, to hospitalized children. The method includes administering to such children an effective amount of one of the nutritional compositions presented herein.
Yet another method refers to reducing the length of hospital stay for patients. The method includes administering an effective amount of one of the nutritional compositions presented here to a hospital patient, such as an elderly patient, to allow such patients to achieve acceptable nutrition levels and feeding goals with greater tolerance for such formulations to increase thereby compliance with food to improve the condition of the patient in order to reduce hospitalization time.
Additional methods include treatments to minimize negative evolution of intestinal microbiotics in elderly individuals due to advanced age by administering an effective amount of one of the nutritional compositions presented here to such individuals to allow such individuals to maintain microbiotic levels for longer despite of his increasing age while also decreasing Clostridium and increasing Bifidobacteria.
The present description also presents a method for increasing the production of butyrate in the colon of a patient, by administering an effective amount of one of the nutritional compositions presented to the patient here to increase the production of butyrate compared to formulations that do not. contain AG to produce proliferation and differentiation of cells in the colon and to lower the pH of the colon to inhibit the growth of pathogenic bacteria to provide anti-inflammatory benefits that help protect the patient's intestinal barrier.
Yet another method concerns the enhancement of an individual's immune function by administering an effective amount of one of the nutritional compositions presented here to decrease Clostridium difficile while the function of T cells, the intestinal-associated lymphoid tissue (GALT) and secretory IgA (slgA) is enhanced to increase the individual's ability to resist disease.
A method for improving tolerance to organ transplantation is also provided by administering to an individual who receives a transplant an effective amount of one of the nutritional compositions presented here to provide specific colonizations that provide unique downward regulation of the immune response and modulation of inflammatory cytokines that lead to decreased lean body mass, whereas GLP-1 and GLP-2 lead to increased insulin release. GLP-1 is insulinotrophic, but GLP-2 has trafficking effects in the intestine, for example, intensified intestinal crypt cell proliferation and villous height, see Martin GR et al., Nutrient-stimulated GLP-2 release and crypt cell proliferation in experimental short bowel syndrome, Am. J. PhysioL, Gastrointest, Liver PhysioL, G431-G438 (2005), and a reduction in the balance between T-helper (TH) 1 and TH 2 cell responses, see Zhao Y, et. al., Th1 and Th2 cytokines in organ transplantation: paradigm lost , Crit Rev Immunol., 1999; 19 (2): 155-72.
Yet another method concerns improving bone growth or preventing bone degradation in a patient in need of it, by increasing the absorption of vitamins and nutrients in an individual's intestines and colon. The method includes administering to pa9 / 72 aware of an effective amount of one of the nutritional compositions presented here to increase the absorption of nutrients such as vitamin D, zinc, or calcium to help improve bone structure, growth and function .
Another method of the present description relates to intensifying a patient's muscle mass by increasing the absorption of vitamins and other nutrients in an individual's intestines and colon. The method includes administration to an individual who desires such enhanced muscle mass and greater absorption of an effective amount of one of the nutritional compositions presented here in order to specifically increase the absorption of vitamins and minerals such as (but not limited to) vitamin D, folate, B12, magnesium or calcium in the individual, to help in improving the general well-being, musculoskeletal health, mobility and cognitive health, in preventing the decrease in muscle mass or in improving the recovery of muscle mass.
The present description also relates to a method for improving an individual's metabolism. The method includes administering to an individual who desires such a metabolism that enhanced an effective amount of one of the nutritional compositions presented herein in order to enhance the absorption of micronutrients, in order to improve the bioavailability of such micronutrients.
The present description also refers to a method to provide a more complete feeling or satiety so that the individual can have a better start in the morning, in order to avoid excess food, decrease caloric intake or provide sustained energy after the administration of composition.
Another method of the present description relates to the treatment of diabetes in a patient in need of such treatment. The method includes administering to such a patient an effective amount of one of the nutritional compositions presented here in order to decrease insulin resistance, so as to decrease blood glucose excursions or decrease the risk of CVD and reduce azotemia in people with renal insufficiency.
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The present description also relates to the use of a polysaccharide, such as a gum including, for example, AG in a nutritional composition that includes a FOS and an inulin for administration to an individual to provide nutrition. The polysaccharide can be present in an effective amount in order to provide a greater tolerance to such nutritional compositions when administered to the individual, in which the polysaccharide, FOS and inulin are present in the amounts presented here.
Another aspect of the present description is the use of a polysaccharide, such as a gum including, for example, acacia gum for the preparation of a nutritional composition to promote intestinal microbiotic balance and health in an individual. The nutritional composition can also include a FOS and an inulin in the amounts presented here.
Additional features and advantages are described here, and will be apparent from the following detailed description and figures.
BRIEF DESCRIPTION OF THE FIGURES
Figure 1 shows the time to reach the target caloric intake in children hospitalized in the pediatric intensive care unit (PICU) receiving mechanical ventilation and enteral feeding containing Mixture ^14- (with probiotics NCC2461 / NCC3001 + prebiotics (PREBIO1 ™ + AG) + DHA) or Mixture ¹ (without pro- and prebiotics or DHA added).
Figure 2 shows a standard configuration of a Human Intestinal Microbial Ecosystem (SHIME) Simulator, which includes five sequential reactors that simulate different regions of the human intestinal tract.
Figures 3A-3F show graphs of the total SCFA, acetate, propionate and butyrate concentrations in the ascending, transverse and descending colon for experiments performed with Mixture ¹ (designated by number 1) and Mixture ^14- (designated by number 2).
Figures 4A-4F show bar graphs of A / P / B ratios in the ascending, transverse and descending colon of experiments performed with Mixture ¹ (designated by the number 1) and Mixture ^14- (designated by the number 2).
Figures 5A-5E show the data for the effects of Mixture ¹
11/72 (designated as SHIME 1) and Mixture ¹ * (designated as SHIME 2) in production in vessels other than the colon of the SHIME experiments. Data are presented per week of experiment. Differences in ACFA concentrations between colon compartments were assessed using a one-way ANOVA, and individual means were compared using the Tukey test.
Figures 6A-6B show bar graphs that graphically represent the ammonium concentrations (MG of NH ₄ 7l_) in the ascending, transverse and descending colon for experiments performed when using Mixture ¹ (designated as SHIME 1) and Mixture ¹ * ( designated as SHIME 2). The data are presented by experiment period. Significant differences in ammonium production (CTRL v. TREAT) were assessed using a Student's two-tailed test and are indicated with * for P <0.05 and ** for P <0.01.
Figures 7A-7B show bar graphs that graphically represent lactate concentrations in the ascending, transverse and descending colon for experiments performed using Mixture ¹ (designated as SHIME 1) and Mixture ¹ * (designated as SHIME 2). The data are presented by experiment period. Significant differences in lactate production (CTRL v. TREAT) were assessed using Student's two-tailed test and are indicated with * for P <0.05.
Figures 8A-8F show the consumption of acid-base in the ascending, transverse and descending colon for experiments performed when using Mixture ¹ (designated as SHIME 1) and Mixture ¹ * (designated as SHIME 2). The data are presented by experiment period.
Figure 9 shows a short-term selection assay consisting of the sequential incubation of a representative dose of the selected compound under simulated conditions for the stomach, small intestine and ascending colon.
Figure 10 shows a group experiment sampling scheme for pH and gas measurements.
Figures 11A-11B show the change in gas production
12/72 total and CO ₂ in the group experiment. Mixture ¹ is designated as A, Mixture ¹⁺ is designated as B. Significant differences (compared to previous sampling points) were assessed using Student's two-tailed test and are indicated with * for P <0, 05.
Figure 12 shows the change in pH in the group experiment that compares the values at time 0 hours and 48 hours. Mixture ¹ is designated as A, Mixture ¹⁺ is designated as B. Significant differences (compared to the other product) were assessed using Student's two-tailed test and are indicated with * for P <0.05.
Figures 13A-13B show the qPCR data for the total bacteria presented per experimental week in each colon compartment. Figure 13A represents data from experiments with Mixture ¹ and figure 13B represents data from experiments with Mixture ¹ *. Where designated by *, the difference from the control mean is statistically significant according to a T-test (p <0.05).
Figures 14A-14B show the qPCR data for the total of Bacteriodetes presented per experimental week in each colon compartment. Figure 14A represents data from experiments with Mixture ¹ and figure 14B represents data from experiments with Mixture ¹ *. Where designated by *, the difference from the control mean is statistically significant according to a T-test (p <0.05).
Figures 15A-15B show the qPCR data for the total of Firmicutes presented per experimental week in each colon compartment. Figure 15A represents data from experiments with Mixture ¹ and figure 15B represents data from experiments with Mixture ¹ *. Where designated by *, the difference from the control mean is statistically significant according to a T-test (p <0.05).
Figures 16A-16B show the qPCR data for the total Lactobacilli presented per experimental week in each colon compartment. Figure 16A represents data from experiments with Mixture ¹ and figure 16B represents data from experiments with Mixture ¹ *. Where designated by *, the difference from the control mean is statistically significant13 / 72 va according to a T-test (p <0.05).
Figures 17A-17B show the qPCR data for the total of Bifidobacteria presented per experimental week in each colon compartment. Figure 17A represents data from experiments with Mixture ¹ and figure 17B represents data from experiments with Mixture ¹ *. Where designated by *, the difference from the control mean is statistically significant according to a T-test (p <0.05).
Figures 18A-18B illustrate comparisons of data from each colon vessel for the two products in a diffusion chart. AC1, TC1, and DC1 refer to Mixture ¹ ; AC2, TC2, and DC2 refer to Mixture ¹ *. Weeks 1-2 were the control period and weeks 3-5 were the treatment period. The red arrow indicates for each group the position of the node in the groove model.
Figures 19A-19B illustrate comparisons of data from each colon vessel for the two products in a diffusion chart. AC1, TC1, and DC1 refer to Mixture ¹ ; AC2, TC2, and DC2 refer to Mixture ¹ *. Weeks 1-2 were the control period and weeks 3-5 were the treatment period. The red arrow indicates for each group the position of the node in the groove model.
Figure 20 is a comparison of the data from each colon vessel for the two products in a diffusion chart. AC1, TC1, and DC1 refer to Mixture ¹ ; AC2, TC2, and DC2 refer to Mixture ¹ *. Weeks 1-2 were the control period and weeks 3-5 were the treatment period. The red arrow indicates for each group the position of the node in the groove model.
DETAILED DESCRIPTION
Definitions
As used in this description and the appended claims, the singular forms one, one and o / a include plural referents unless the context clearly dictates otherwise. Thus, for example, the reference to an amino acid includes a mixture of two or more amino acids, and the like.
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As used herein, about should be understood as referring to numbers on a scale of numerals. In addition, all numerical scales here must be understood to include any whole number or fractions, within the range.
As used herein, the term amino acid is to be understood to include one or more amino acids. The amino acid can be, for example, alanine, arginine, asparagine, aspartate, citrulline, cysteine, glutamate, glutamine, glycine, histidine, hydroxyproline, hydroxyiserine, hydroxytyrosine, hydroxylysine, isoleucine, leucine, lysine, methionine, phenylalanine, praline, serine, proline taurine, threonine, tryptophan, tyrosine, valine, or combinations thereof.
As used herein, an animal includes, but is not limited to, mammals, which include, but are not limited to, rodents, aquatic mammals, domestic animals such as dogs and cats, farm animals such as sheep, pigs, cows and horses, and humans. Where the terms animal or mammal or its plurals are used, it is contemplated that they also apply to all animals that have the capacity of the effect displayed or that are intended to be displayed by the context of the passage.
As used herein, the term antioxidant should be understood to include any one or more of several substances such as beta-carotene (a precursor to vitamin A), vitamin C, vitamin E, and selenium which inhibit oxidation or the reactions promoted by the Reactive Oxygen Species (ROS) and other radical and non-radical species. In addition, antioxidants are molecules capable of slowing or preventing the oxidation of other molecules. Non-limiting examples of antioxidants include carotenoids, coenzyme Q10 (CoQ10), flavonoids, Goji glutathione (barium lice), hesperidin, lactogoji, lignan, lutein, lycopenp, polyphenols, selenium, vitamin A, vitamin B1, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, zeaxanthin, or combinations of these.
As used herein, complete nutrition refers to the
15/72 nutritional products that contain sufficient types and levels of macronutrients (protein, fats and carbohydrates) and micronutrients to be sufficient as a single source of nutrition for the animal to which they are administered.
As used herein, an effective amount is an amount that prevents a deficiency, treats a disease or medical condition in an individual, or, more generally, reduces symptoms, controls disease progression or provides a nutritional, physiological or medical benefit to the individual. individual. A treatment can be related to the patient or the doctor.
As used herein, incomplete nutrition refers to nutritional products that do not contain sufficient levels of macronutrients (protein, fats and carbohydrates) or micronutrients to be sufficient as a single source of nutrition for the animal to which they are administered.
Although the terms individual and patient are used here frequently to refer to a human being, the invention is not thus limited. Therefore, the terms individual and patient refer to any animal, mammal or human being who has or is at risk for a medical condition that may benefit from treatment.
As used herein, non-limiting examples of fish oils include docosahexenoic acid (DHA) and eicosapentenoic acid (EPA). DHA and EPA may also be present from an oil source other than fish (eg, algae, modified plants, etc.).
As used herein, food grade microorganisms refer to the microorganisms that are used and generally considered to be safe for use in food.
As used herein, long-term administrations are continuous administrations for more than six weeks.
As used herein, a mammal includes, but is not limited to, rodents, aquatic mammals, domestic animals such as
16/72 dogs and cats, farm animals such as sheep, pigs, cows and horses, and humans. Where the term mammal, it is contemplated that it also applies to other animals that have the capacity of the effect exhibited or that are intended to be exhibited by the mammal.
The term microorganism lends itself to include bacteria, yeast and / or fungi, a cell growth medium with the microorganism, or a cell growth medium in which the microorganism was grown.
As used herein, the term minerals should be understood to include boron, calcium, chromium, copper, iodine, iron, magnesium, manganese, molybdenum, nickel, phosphorus, potassium, selenium, silicon, tin, vanadium, zinc, or combinations thereof.
Nutritional compositions, as used herein, are to be understood to include any number of optional additional ingredients, including conventional food additives, for example, one or more acidulants, additional thickeners, buffering agents or pH adjusting agents, chelation, dyes, emulsifiers, excipients, flavoring agents, minerals, osmotic agents, a pharmaceutically acceptable carrier, preservatives, stabilizers, sugars, sweeteners, texturizers, and / or vitamins. Optional ingredients can be added in any appropriate amount.
As used herein the term patient is to be understood to include an animal, especially a mammal, and more especially a human being receiving or intended to receive treatment, as defined herein.
As used herein, phytochemicals or phytonutrients are the non-nutritive compounds that are found in many foods. Phytochemicals are functional foods that have health benefits in addition to basic nutrition, and are health-promoting compounds that come from plant sources. As used herein, phytochemicals and phytonutrients refer to any chemical product produced by a plant that provides one or more health benefits to the user. Phytochemicals
17/72 can be administered by any means, including topically, enterally and / or parenterally. As used herein, non-limiting examples of phytochemicals and phytonutrients include those that are i) phenolic compounds that include monophenols (such as: Apiole, Carnosol, Carvacrol, Dillapiole, Rosemarinol); Flavonoids (polyphenols) including Flavonols (such as: Quercetin, Gingerol, kaempferol, myricetin, rutin, Isorramnetina), flavanones (such as: Hesperidin, naringenin, Silibine, Eriodictiol), flavones (such as: Apigenin, Tangeritine, Flute) -3-ols (such as: Catechins, (+) - Catechins, (+) - Galocatechins, (-) - Epicatechins, (-) Epigallocatechins, (-) - epigallocatechins (EGCG), (- 3-gallate) ) epicatechin, teaflavine, teaflavine 3-gallate, teaflavine 3-gallate, teaflavine 3,3-gallate, Tearubigins), anthocyanins (flavonal) and anthocyanides (such as: Pelargonidine, peonidine, cyanidine, delfinidine, malvidin, petunidine, ), isoflavones (phytoestrogens) (such as: Daidzein (formononetin), Genistein (biocanine A), Glycitein), Dihydroflavonols, chalcones, Coumestanas (phytoestrogens), and Coumestrol; Phenolic acids (such as: Ellagic acid, gallic acid, tannic acid, vanillin, curcumin); Hydroxycinnamic acids (such as: Caffeic acid, chlorogenic acid, cinnamic acid, ferulic acid, coumarin); Lignans (phytoestrogens), Silymarin, Secoisolariciresinol, Pinoresinol and lariciresinol); Tyrosol esters (such as: Tyrosol, Hydroxytyrosol, Oleocantal, Oleuropein); Stilbenoids (such as: Resveratrol, Pterostilbeno, Piceatanol) and Punicalaginas; ii) Terpenes (isoprenoids) that include carotenoids (tetraterpenoids) including carotenes (such as: α-carotene, β-carotene, γ-carotene, δ-carotene, lycopene, Neurosporene, phytofluene, phytoene), and xanthophylls (such as: Canthaxanthin, Cryptoxanthine , Zeaxanthin, Astaxanthin, Lutein, Rubixanthin); Monoterpenes (such as: Limonene, peryl alcohol); Saponins; Lipids including: Phytosterols (such as: Campesterol, beta sitosterol, gamma sitosterol stigmasterol), tocopherols (vitamin E), and omega-3, -6 and -9 fatty acids (such as: gamma-linolenic acid); Triterpenoids (such as: Oleanolic acid, ursolic acid, betulinic acid, moronic acid); iii) Betalains that include betacyanins (such as: betanine, isobetanine, probetanin, neobetanine); and Betaxanthines (non-glycosidic versions 18/72 cas) (such as: Indicaxanthin and Vulgaxanthin); iv) Organosulfides that include Dithiolthiones (isothiocyanates) (such as: Sulforaphane); and thiosulfonates (allium compounds) (such as: Allyl methyl trisulfide, and diallyl sulfide), Indoles, glucosinolates which include indol-3-carbinol; sulforaphane; 3,3'Diindolylmethane; Sinigrin; Allicin; Aliina; Allyl isothiocyanate; Piperine; Sinpropanothial-S-oxide; v) Protein inhibitors that include protease inhibitors; vi) other organic acids that include oxalic acid, phytic acid (inositol hexaphosphate); Tartaric acid; and anacardic acid; or combinations of these.
As used herein, a prebiotic is a food substance that selectively promotes the growth of beneficial bacteria or inhibits the growth or mucosal adhesion of pathogenic bacteria in the intestines. They are not inactivated in the stomach and / or the upper intestine nor are they absorbed in the gastrointestinal tract of the person who ingests them, but fermented by the gastrointestinal microflora and / or probiotics. Prebiotic, is defined, for example, by Glenn R. Gibson and Marcei B. Roberfroid, Dietary Modulation of the Human Colonic Microbiota: Introducing the Concept of Prebiotics, J. Nutr. 1995 125: 1401-1412. Non-limiting examples of prebiotics include acacia gum, alpha glucan, arabinogalactans, beta glucan, dextrans, fructooligosaccharides, fucosylactose, galactooligosaccharides, galactomannans, gentiooligosaccharides, glucooligosaccharides, guar gum, inulin, lactam, lactam, lactam, lactam, lactam, lactam maltodextrins, milk oligosaccharides, partially hydrolyzed guar gum, pecticoligosaccharides, resistant starches, retrograded starches, sialooligosaccharides, siallylactose, soioligosaccharides, sugar alcohols, xylooligosaccharides, or their combinations.
As used herein, probiotic microorganisms (hereinafter, probiotics) are food grade microorganisms (live, including semi-viable or weakened, and / or non-replicable), metabolites, microbial cell preparations or components of microbial cells that can confer health benefits on the host when ad19 / 72 administered in adequate amounts, more specifically, that beneficially affect a host by improving its intestinal microbial balance, leading to effects on the health or well-being of the host. See Salminen S, Ouwehand A. Benno Y. et al., Probiotics: how should they be defined , Trends Food Sei. Technol., 1999: 10, 107-10. In general, it is believed that these microorganisms inhibit or influence the growth and / or metabolism of pathogenic bacteria in the intestinal tract. Probiotics can also activate the host's immune function. For this reason, there are many different approaches to including probiotics in food products. Non-limiting examples of probiotics include Aerococcus, Aspergillus, Bacillus, Bacteroides, Bifidobacterium, Candida, Clostridium, Debaromyces, Enterococcus, Fusobacterium, Lactobacillus, Lactococcus, Leuconostoc, Melissococcus, Pepsi, , Pseudocatenulatum, Rhizopus, Saccharomyces, Staphylococcus, Streptococcus, Torulopsis, Weissella, or combinations thereof.
The terms protein, peptide, oligopeptides or polypeptide, as used herein, are to be understood as referring to any composition that includes a single amino acid (monomer), two or more amino acids joined together by a peptide bond (tripeptide dipeptide, or polypeptide), collagen, precursor, homologue, analog, mimetics, salt, prodrug, metabolite, or fragment thereof, or combinations thereof. For the sake of clarity, the use of some of the above terms is interchangeable, unless otherwise specified. It should be appreciated that polypeptides (or peptides or proteins or oligopeptides) often contain amino acids with the exception of the 20 amino acids normally indicated as the 20 naturally occurring amino acids, and that many amino acids, including terminal amino acids, can be modified in a given polypeptide, both by natural processes such as glycosylation and other post-translational modifications, and by chemical modification techniques that are well known in the prior art. Known modifications that may be present in the po20 / 72 lipeptides of the present invention include, but are not limited to, acetylation, acylation, ADP-ribosylation, amidation, covalent attachment of a flavonoid or a portion heme, the covalent bond of a polynucleotide or polynucleotide derivative, the covalent bond of a lipid or a lipid derivative, the covalent bond of phosphatidylinositol, cross-linking, cyclization, the formation of disulfide bonds, demethylation, the formation of cross-links covalent, cystine formation, pyroglutamate formation, formylation, gamma-carboxylation, glycation, glycosylation, glycosylphosphatidyl inositol (GPI) membrane anchor formation, hydroxylation, iodination, methylation, myristylation , oxidation, proteolytic processing, phosphorylation, prenylation, racemization, selenylation, sulfation, RNA transfer-mediated addition of amino acids to polypeptides such as arginylation and ubiquitination. The term protein also includes artificial proteins that refer to linear or non-linear polypeptides, which consist of alternating repeats of a peptide.
Non-limiting examples of proteins include dairy-based proteins, plant-based proteins, animal-based proteins and artificial proteins. Proteins based on dairy products include, for example, casein, caseinates (for example, all forms including sodium, calcium, and potassium caseinates), casein hydrolysates, buttermilk (for example, all forms including concentrated, isolated and demineralized), buttermilk hydrolysates, milk protein concentrate, and milk protein isolate. Plant-based proteins include, for example, soy protein (for example, all forms including concentrated and isolated), pea protein (for example, all forms including concentrated and isolated), canola (for example, all forms including concentrated and isolated), other plant proteins that are commercially wheat and fractionated wheat proteins, corn proteins and their fractions including zein, rice, oats, potatoes, peanuts , powdered green peas, powdered beans, and all proteins derived from beans, lentils and legumes21 / 72 sas.
As used herein, short-term administrations are continuous administrations for less than six weeks.
As used here, a symbiotic is a supplement that contains a prebiotic and a probiotic that work together to improve the microflora of the intestine.
As used herein, the terms treatment, treating ³ 'and relieving include prophylactic or preventive treatment (which prevents and / or delays the development of a target pathological condition or disorder) and curative, therapeutic or disease-modifying treatment, including therapeutic measures that cure, delay, decrease symptoms and / or stop the progression of a condition or pathological disorder diagnosed; and the treatment of patients at risk of contracting a disease or suspected of having contracted a disease, as well as of patients who are ill or have been diagnosed as suffering from a disease or medical condition. The term does not necessarily imply that an individual is treated until full recovery. The terms treatment and treat also refer to maintaining and / or promoting health in an individual who does not suffer from a disease but who may be susceptible to the development of an unhealthy condition, such as nitrogen imbalance or muscle loss. The terms treatment, treat and alleviate are also suitable to include the enhancement or or the intensification of one or more prophylactic or primary therapeutic measures. The terms treatment, treat and alleviate also include the dietary management of a disease or condition or dietary management for the prophylaxis or prevention of a disease or condition.
As used herein, tube feeding is a nutritional product or a complete or incomplete composition that is administered to an animal's gastrointestinal system, other than through oral administration, including, but not limited to, a nasogastric tube, a orogastric tube, gastric tube, jejunostomy tube (J-tube), percutaneous endoscopic stomach conduit opening surgery
22/72 (PEG), door, such as a chest wall door that provides access to the stomach, fasting and other appropriate access doors.
As used herein, the term vitamin should be understood to include any of several organic substances soluble in fat or water soluble (the non-limiting examples of which include vitamin A, vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin or niacinamide), vitamin B5 (pantothenic acid), vitamin B6 (pyridoxine, pyridoxal or pyridoxamine, or pyridoxine hydrochloride), vitamin B7 (biotin), vitamin B9 (folic acid), and vitamin B12 (various cobalamines; usually cyanocobalamin in vitamin supplements), vitamin C, vitamin D, vitamin E, vitamin K, folic acid and biotin) essential in minuscule amounts for normal growth and activity body and obtained naturally from food derived from plants and animals or produced synthetically, pro-vitamins, derivatives, analogues.
Enteral Nutrition
Enteral nutrition is the preferred method of applying nutrients to individuals who are unable to orally satisfy their nutritional needs. A standard formula is most commonly used in individuals with no specific medical interest. These formulas have levels of macro- and micronutrients that satisfy the recommendations for a healthy population and are generally well tolerated. In the past, fiber-free enteral formulas were preferred due to problems with clogging the tubes, as well as the notion that resting the intestine was beneficial. Since most of the fiber clogging problems have since been eliminated, it is now recognized that fiber can be included in such formulations in order to exert a number of beneficial physiological effects that are desirable for this population.
Direct benefits of fiber
Fiber increases the water content and the volume of food contents, normalizing the progression of bowel movement through the intestine. In this way, dietary fiber contributes in order to improve the regularity of
23/72 bowel movements, facilitating the generation of soft formed stools, and increasing the ease and control of stool evacuation. In addition, soluble viscous fibers have a number of metabolic benefits, including cholesterol-lowering effects. The presence of these fibers increases the viscosity of the intestinal contents and can interfere with the absorption of bile acids in the ileum, causing an increase in the acid loss of fecal bile. As a result, LDL cholesterol is removed from the blood by the liver and converted to bile acids to compensate for this loss. Similarly, viscous fibers can also attenuate the glucose and insulin response to nutrient intake. These fibers can increase the viscosity of the stomach, thereby delaying gastric emptying. In addition, the increased chyme viscosity slows down the intestinal glucose absorption rate and reduces the need for insulin. With the increase in viscosity of the stomach contents, these fibers also reduce the number of episodes of gastroesophageal reflux, regurgitation and vomiting, which increases the tolerance to enteral feeding.
Indirect fiber benefits
About 100 trillion microorganisms are present in the gut of a typical adult. The balance between beneficial and pathogenic bacteria is extremely important for maintaining normal intestinal physiology, because this balance has direct effects on immune function and digestion and nutrient absorption. By definition, a prebiotic substance is a selectively fermented ingredient that allows for specific changes, both in composition and / or in activity in gastrointestinal microbiotes that confer benefits on the host's well-being and health. This typically refers to an increase in Bifidobacteria and / or lactobacilli. The benefits of prebiotic substances (or abbreviated prebiotics) include:
(1) an improvement in the mucosal barrier function, helping to prevent the translocation of bacteria to the bloodstream;
(2) promoting benefits and reducing pathogenic bacterial subpopulations;
24/72 (3) the production of SCFA, for example, butyrate, the main source of energy for epithelial cells in the large intestine; SCFA also help to regulate the absorption of Na + and water; and (4) an improvement in host immunity, through interactions between intestinal immunological cells and pathogenic bacteria. Benefits of Dietary Fibers in Clinical Nutrition
Diarrhea and constipation are common complaints among patients who take fiber-free enteral formulas. It has been shown that fibers normalize defecation frequency and transit time, and the fiber can thus be added to formulas to promote regularity. A recent meta-analysis including 51 studies of fiber-supplemented enteral formulas revealed that fiber administration reduced the incidence of diarrhea and increased the frequency of bowel movements when low, which supports a moderating effect on fiber in bowel function. Likewise, an expert consensus panel recommended the inclusion of fiber in the diets of all patients if there is no contraindication, based on the benefits of diarrhea, constipation, and tolerance to food. See ESPEN, Guidelines 2006. Additional fiber benefits include improved bowel barrier function, colon epithelial proliferation, enhanced fluid and electrolyte absorption, relieved gastroesophageal reflux, regurgitation and vomiting, improving food tolerance enteral and benefits in glycemic control and serum lipid parameters. On the other hand, fiber supplementation has sometimes been reported to cause gastrointestinal side effects such as bloating and flatulence. Therefore, it is important to include fiber types and amounts with minimal gastrointestinal side effects.
Since it is well recognized that different fibers have different health effects, the use of fiber mixtures has become increasingly common. The mixtures are believed to be much more like a normal mixed diet and allow a range of physiological effects to be achieved. There is currently no official recommendation regarding the relationship between soluble and insoluble fibers, although it is estimated that in a diet
25/72 mixed about 30% of the consumed fibers are soluble.
Nestlé Healthcare Nutrition's Standard Tube Feeding fiber blend is specifically designed to maximize health benefits while optimizing gastrointestinal tolerance and ensuring acceptable viscosity and flow rates. The blend meets current recommendations by providing 15 g / l of the formula's fiber and a mixture of soluble and insoluble fibers. The soluble component of the fiber blend is designed to build and improve with the scientific and brand equity of Nestlé's Branded Active Benefit, the PREBIO1 ™ additive, which is a 70:30 mixture of fructooligosaccharides (FOS) and inulin, which are low-viscosity soluble fibers obtained from chicory. These molecules are linear fructans that contain glycosidic bonds of β (2-1) fructosyl-fructose. Inulin (included at 1.5 g / l) refers to molecules with an average SD = 10, while FOS (included at 3 g / l) has a lower DP and can be obtained as a product of hydrolysis of inulin or by the synthesis of fructose or fructose and glucose.
Both FOS and inulin have been studied extensively as prebiotics, with bifidogenic effects observed at doses as low as 4 g / d. Both are readily fermentable and appear to increase the production of propionate and butyrate, which is considered most beneficial to colon health. These fibers have some swelling properties, and the addition of FOS to an enteral formula has been shown to reduce constipation. Inulin and FOS also appear to benefit immune function. Inflammation and expression of pro-inflammatory cytokines were reduced in patients with ulcerative colitis who consume 6 g / d of a FOS / inulin mixture, and elderly nursing home patients who received 8 g / d of FOS saw an improvement in the immune response as indicated by an increase in T lymphocytes. In addition, mixtures of these fibers (8 g / d or more) have been shown to increase the absorption of minerals, for example, the absorption of calcium, magnesium, zinc or iron , mainly in adolescents and postmenopausal women, which results in reduced blood pressure and improves cardiovascular health, as well as a better me26 / 72
Better bone mineralization. For best FOS results, however, daily intake should vary between 5 and 10 grams a day, as dosages above 15 grams can cause gas or intestinal cramps with an excess of Bifidobacteria populations. It has been found that the tolerance to G1 due to gas production is improved when FOS / inulin mixtures are used compared to using either alone.
The present description provides a nutritious composition with the dose of these fibers below that which has been shown to cause intestinal discomfort, while still conferring prebiotic benefits. As discussed in the following section, the addition of AG to the nutritional composition of the present description allows the use of low doses of inulin and FOS while increasing the total fiber content and providing a greater overall prebiotic benefit.
Standard Tube Feed Mixing
The present description presents a new and improved composition that comprises a 70:30 ratio between FOS and inulin (PREBIO1 ™) and a 1: 1 ratio between FOS and AG. This provides a range of short (FOS), medium (inulin), and long (AG) fibers which are fermented at different rates, thereby conferring benefits along the entire length of the colon.
AG, also known as Acacia gum, acacia gum, Arabic or Indian gum, is a natural, non-viscous soluble fiber that belongs to the complex family of arabinogalactan. AG is a highly branched molecule of high molecular weight that comprises units of galactose, arabinose, rhamnose and glucuronic acid. This native substance has an average molecular weight between 300 and 800 kDa. It is composed of 95% dry weight polysaccharides and 1 to 2% depending on the species of proteins. AG is composed of three different fractions, that is, 1% glycoprotein, 1-10% arabinogalactan-protein, and 90-99% arabinogalactan. AG is fermented slowly compared to other soluble fibers and increases SCFA production, and therefore can benefit the distal colon. Low doses of AG (3 g / d) have been shown to be prebiotic when
27/72 combined with 3 g / d of FOS. Animal studies suggest AG's ability to improve diarrhea symptoms, and human experiments have shown effects on normalizing bowel function. In addition, it has been shown that 5 g of AG added to a meal reduces the glycemic response, and chronic consumption of 25 g / d has a lipid-lowering effect.
Individuals generally have a very high gastrointestinal tolerance to AG, where administration of up to 70 g / d does not cause any major side effects in healthy individuals. It was found that the combination of FOS and AG at a 1: 1 ratio, as provided in the composition of the present description, reduces the side effects of Gl, such as stomach bloating and discomfort, compared to FOS alone, while which at the same time confers a synergistic prebiotic benefit. In this way, AG can provide partial replacement for FOS to offer prebiotic benefits without the problems of tolerance. In addition, AG can also protect FOS from hydrolysis and help to reduce the viscosity of soy and other fibers such as the outer fiber of peas. AG is believed to act in a manner similar to an emulsifier to improve the performance of FOS in such compositions. Therefore, the addition of highly complex high molecular weight AG improves bowel comfort while increasing the prebiotic benefit of FOS fibers.
AG also provides a number of unexpected benefits in the formulations of the present description. For example, it has been found that AG in the amounts described herein protects the FOS from hydrolysis, thereby maintaining the FOS in a form that is active after administration to the individual. AG is also believed to help maintain the viscosity of the formulation when other fibers such as soy fibers or pea fibers are present. The additional advantages of AG include its relatively low viscosity in water, its high solubility at room temperature, its neutral taste, color and odor, and its ability to improve mouthfeel and enhance flavor release (when used with flavorings).
In the past, the rapid fermentation of inulin and FOS was as28 / 72 associated with excess gas and the discomfort of Gl, thereby limiting the dose of prebiotic fibers that can be added to the products. Advantageously, the use of slowly fermented AG allows the application of a higher dose of prebiotic fibers without the associated intolerance to Gl. In addition, it has been shown that the use of a ratio between AG and FOS in a ratio of about 1: 1 promotes a synergistic prebiotic effect, as well as a greater gastrointestinal tolerance, thus making this combination of soluble fibers ideal for addition to enteral formulas.
One of the main problems in enteral nutrition is the occurrence of diarrhea and other gastrointestinal side effects during nutrition. There are reports on the rate of diarrhea between 2% and 67% of patients receiving enteral nutrition. See Patty Eisenberg, An OverView of Diarrhea in the Patient Receiving Enteral Nutrition, Gastroenterology Nursing, 25 (3): 95-104 (2002).
The composition of the present description uses strong prebiotic fibers with a range of molecular weights (from very small to very large) and fermentation speeds (from fast to slow), which allow SCFA production and prebiotic effects to be maintained throughout the entire length of the colon.
The amounts of FOS, inulin and AG may vary, as long as they fall within the claimed ratios. As indicated here, the quantities of each of the FOS or AG can be within the range of 1.5 to 10 g / l, but they can also be between 3 and 5.5 g / l. Inulin can vary between 0.5 and 5 g / l, but can also be between 1 and 2.5 g / l. These amounts used within the claimed ratios are well tolerated by the individuals to whom the compositions are administered.
In another embodiment, the composition of the present description further comprises insoluble outer pea fibers. The outer fiber of the pea is an insoluble fiber obtained from the pea shell and can be included in an amount between 5 and 10 g / l, or between 7 and 8 g / l, or about 7.5 g / l. The outer fiber of the pea is composed mainly of hemicelluloses rich in arabinose, cellulose, and pectic substances, such as
29/72 uronic acid. The addition of 4 g / d of pea husk fiber to the diet of elderly institutionalized residents significantly increased the frequency of the intestine and decreased the need for the use of laxatives (administration of prune puree) compared to the baseline. It has also been shown to increase the weight of feces in humans and animals. It has also been found that adding pea husk fiber (10 g) to a meal reduces postprandial serum cholesterol levels.
The addition of insoluble fibers such as the outer fibers of peas, soy protein, cellulose, or hemicellulose provides benefits in regularity and in fecal enlargement. In order to provide effective doses of prebiotic fibers and optimize GI tolerance and technical performance, the ratio of soluble / insoluble fibers can be adjusted to 50:50. A modality of such a composition is shown in Table 1. The amount of fiber offered by the mixture in a complete diet meets the recommendations stipulated by several professional associations such as:
(a) European Society for Parenteral and Enteral Nutrition (ESPEN): Patients with normal bowel function, including post-surgery patients, can benefit from the added fiber; 10-15 g fiber / l is an appropriate minimum amount;
(b) Institute of Medicine (IOM) and American Dietetic Association (ADA): 14 g of fiber / 1,000 kcal; and (c) American Diabetes Association (ADA): 15-25 g of fiber / 1,000 kcal.
Table 1: Composition of the feed mix by standard tube (adult and pediatric formula) *
/ Fiber Type ζ-Λ ' Quantity (g)• in 1 liter ‘Quantity (g) in 1.51 (complete feed) FOS 3 4.5 Inulin 1.5 2.25 Acacia Gum 3 4.5 Pea External Fiber (source of cellulose, hemicellulose and pectin) 7.5 11.25 Total 15 22.5
* Assuming the isocaloric formula (1.0-1.2 Kcal / ml)
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Renal Fiber Mixture
Patients with end-stage kidney disease suffer from digestive disorders, especially from constipation. About 50% of patients with end-stage kidney disease suffer from constipation. See Murtagh FEM, Addington-Hall J, Higginson IJ. The Prevalence of Symptoms in EndStage Renal Disease: A Systematic Review. Advances in Chronic Kidney Disease 2007; 14 (1): 82-89. PHGG is a unique water-soluble dietary fiber that is extracted from guar gum. The original high viscosity of guar gum is almost eliminated after hydrolysis, making it an ideal addition to liquid foods and nutritional formulas. There is data to support the PHGG benefit for bowel regularity, and constipation in particular. Many of the beneficial effects of PHGG are probably due to its complete fermentation in the colon, which produces significantly more butyrate than other soluble fibers. See Velazquez M, Davies C, Marett R, Slavin J, Feirtag J. Effect of oligosaccharides and fiber substitutes on short Chain fatty acid production by human faeca microflora. Anaerobe 2000; 6 (2): 87-92. As with other soluble fibers that are rapidly fermented in the proximal colon, PHGG does not significantly increase the weight of the stool. However, a number of studies have shown that PHGG is beneficial in normalizing bowel function, preventing or relieving diarrhea and constipation, especially in patients receiving enteral nutrition and other high-risk populations. See Slavin JL, Greenberg NA. 2003. Partially Hydrolized Guar Gum: Clinicai Nutrition Uses. Nutrition; 19: 549-552.
In a double blind randomized clinical trial, the influence of a soluble fiber, PHGG, on the rate of diarrhea in medical and surgical patients was assessed. Thirty of the hundred patients received total gastrointestinal surgery (TEN) after upper gastrointestinal surgery, 70 patients received supplemental enteral nutrition of 1,000 ml / d. Diarrhea occurred in 15 of the patients fed without fiber (30%) and in 6 of the patients fed with fiber (12%) (P <0.05). In the fiber-free diet group, 40.6 days were observed in which patients suffered from
31/72 diarrhea, and 10.2 days were observed in the supplemented group (P <0.05, P <0.05). The evacuation of enteral nutrition because of the side effects of Gl was significantly more frequently in the fiber-free group of patients who received TEN than in the supplemented group. The use of PHGG lowered the rate of diarrhea in patients with total enteral nutrition, as well as supplemental. In addition, when diarrhea occurred in patients with enteral nutrition supplemented with fiber, the duration was shorter.
In a study of long-term nursing home residents with enemas-controlled constipation, daily supplementation with PHGG (18 g) resulted in a significant decrease in enema requirements in residents with greater use of the enema at baseline. See Soriano CV, Hibler KD, Maxey Kl. Long-term fiber intervention program: reduction in enema use at a developmental care facility. Journal of the American Dietetic Association 2000S; 100 (9): A82. In addition, PHGG (8-12 g per day) decreased the occurrence of constipation and significantly reduced laxative use in elderly nursing home residents who were taking laxatives on a daily basis. See Patrick P, Gohman S, Marx S, DeLegge M, Greenberg N. Effect of Supplements of Partially Hydrolized Guar Gum on the Occurrence of Constipation and Use of Laxative Agents. Journal of the American Dietetic Association 1998; 98 (8): 912-914. Similarly, daily intake of 11 g of PHGG increased the frequency of bowel movements in women with constipation. See Takahashi H, Yang S, Hayaski C, Kim M, Yamanaka J, Yamamoto T. Influence of partially hydrolized guar gum on constipation in women. Journal of Nutritional Science and Vitaminology 1994; 40: 251-259. PHGG has also been shown to reduce the symptoms of irritable bowel syndrome, as well as increased production of Bifidobacterium in the intestine.
In addition, it has also been shown that the use of PHGG relieves abdominal pain and improves bowel habits in adults with Irritable Bowel Syndrome (IBS). Most of the individuals in this study had IBS with a predominance of constipation. Subjects who received 5 g
32/72 per day of PHGG reported a greater subjective improvement compared to individuals who received wheat bran. See Parisi G, Zilli M, Miani M et al. High-fiber diet supplementation in patients with irritable bowel syndrome (IBS): a multicenter, randomized, open trial comparison between wheat bran diet and partially hydrolized guar gum (PHGG). Dig Dis Sei 2002; 47 (8): 1697-704.
A number of compositions have been developed. As used herein, the composition indicated as a renal fiber mixture is not intended to be limited to renal patients; it is aimed at groups of patients who can benefit from such a mixture. For example, the mixture of renal fibers also provides benefits for glycemic control and, therefore, in one modality, it is intended for patients with acute or chronic renal failure, who also often have hyperglycemia or stress-induced diabetes mellitus. Alternatively, the renal fiber mixture, since it confers glycemic benefits, is also intended, in one mode, for patients with hyperglycemia or diabetes mellitus without acute or chronic renal failure. In one embodiment, the composition of the present description is a mixture of renal fibers which also comprises PHGG. In one embodiment, the renal fiber blend of the present description comprises 3-5.5 g / l of FOS, 1-2.5 g / l of inulin, 3-5.5 g / l of AG, and 0-10 g / l of PHGG.
In another embodiment, the renal fiber blend of the present description comprises 4.12 g / l of FOS, 1.76 g / l of inulin, 4.12 g / l of AG, and 7 g / l of PHGG.
In yet another embodiment, the renal fiber blend of the present description comprises 4.12 g / l of FOS, 1.76 g / l of inulin, 4.12 g / l of AG, and 5 g / l of PHGG.
In an additional embodiment, the renal fiber blend of the present description comprises 4.12 g / l of FOS, 1.76 g / l of inulin, 4.12 g / l of AG, and 2.6 g / l of PHGG .
In yet another embodiment, the renal fiber blend of the present description comprises 4.0 g / l of FOS, 1.76 g / l of inulin, and 4.0 g / l of AG.
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The nutritional compositions of the present description can be prepared in liquid form. Although water is the most common vehicle for the other components, it is also contemplated the addition of the compositions to other liquids such as milk, fruit juices, coffee, tea or other drinks when such compositions are administered orally. Water is typically used for other enteral formulations.
The present description also features dry powder formulations. These powder formulations can be obtained by combining dry powder ingredients or they can be obtained from one of the liquid nutritional compositions described herein. Typically, powder formulations are prepared by drying liquid nutritive compositions using spray drying, freeze drying or other drying techniques. If desired, other nutritional components or compositions can be added to the liquid prior to drying to provide greater nutritional benefits to the powder formulation. Such powder formulations have a much longer shelf life and can be packaged for storage and transportation for future use. At that time, powder formulations can be reconstituted with water or other liquids and then administered to the individual orally. The powder formulation can be packaged in a number of containers, including those for the bulk supply of such powder formulations for addition to a liquid in a glass, bottle or other vessel containing fluid, or a single dose can be provided with the powder present in a container to which water or other liquids can be added to form the liquid for oral administration.
It is also contemplated that several conventional additives can be included in the liquid formulations of the present description. For example, various flavorings, vitamins, minerals, antioxidants, preservatives or health-promoting additives can be included in conventional amounts for their conventional purposes.
The compositions of the present description can also be administered to individuals to increase probiotic stability. This benefit is particularly useful for powdered products, in such a way that
34/72 nutritional powdered compositions can be reconstituted when the individual wishes to consume the product to help maintain probiotic stability.
The nutritional compositions of the present description are generally used to promote the health of intestinal microbiotes. The experimental data showed that the nutritional composition of the present description is well tolerated when provided enterally. In particular, the present nutritional compositions confer a greater tolerance to PREBIO1 ™, as well as greater prebiotic benefits.
The composition of the present description can be included as a partial or complete nutritional composition for use in enteral formulations that are administered to provide nutrition to HIV patients, intensive care unit (ICU) and pediatric patients, as well as to improve the health of the patient. intestine. It was found that the weight gain resumed is improved in such patients, most likely due to the greater tolerance to the compositions. It is also believed that the individual's immunity is enhanced due to the improved microbiotic balance that is obtained after administration of the compositions.
The nutritional composition of the present description can also be used to improve the tolerance of the various treatments that lead to GI disorders, such as radiation therapy, chemotherapy, antibiotics, diarrhea treatments, gastrointestinal surgery, anesthesia, and analgesic drugs. The nutritional composition can also confer systemic benefits, such as better growth resumed in hospitalized children.
The nutritional compositions of the present description can also be administered to assist patients in controlling the absorption of Na / H ₂ O or minerals in their intestines, as well as normalizing transit time. These advances in improving bowel function also lead to a reduction in the side effects of the various drugs that are administered for different treatments, since these drugs are eliminated more efficiently from the individual. These improvements are believed to be at least in part due to the AG's ability to provide a greater amount of butyrate in the patient's intestines. AG checks quantities
35/72 butyrate compared to pectin, wheat bran, ispagula or cellulose. On the other hand, FOS produces mainly acetates instead of butyrates, and acetates are metabolized by the liver. Inulin and PHGG also produce butyrates. Butyrates are desirable because they are the main fuel for colon cells to produce cell proliferation. Butyrates also lower the pH of the colon in order to inhibit the growth of pathogenic bacteria. This results in anti-inflammatory benefits that help protect the gut barrier.
For elderly patients, for example, those over 65 years of age, administration of the nutritional compositions of the present description allows such patients to achieve acceptable levels of nutrition and feeding goals with greater tolerance to such formulations. For hospitalized patients, the achievement of feeding goals and the provision of adequate nutrition typically lead to a shorter period of hospital stay, greater compliance with feeding requirements, and fewer complications such as diarrhea or constipation. The shorter hospital stay leads to reduced costs for both the patient and the insurer.
Administration of the nutritional compositions of the present description also minimizes the negative evolution of the gut microbiotas due to the individual's older age. This allows individuals receiving such compositions to maintain healthy levels of microbiotes for longer despite their growing age. In addition, Clostridium decreases, while Bifidobacteria increases.
Administration of the present nutritional compositions presented herein can also enhance an individual's immune system. In particular, Clostridium difficile is decreased, while the function of T and GALT cells is increased. The adaptive immunity of the slhA individual and the immunity of inpatients are increased, in such a way as to increase the individual's ability to resist the disease. The specific colonizations that are provided by the present compositions provide a
36/72 singular upward regulation in such a way that the inflammatory cytokine leads to less lean body mass, GLP-1 and GLP-2 lead to increased insulin resistance, and the TH1 / TH2 imbalance is reduced. It is believed that these benefits will lead to better transplant tolerance in such individuals.
Yet another method refers to improving bone growth or preventing bone degradation in a patient in need of it by increasing the absorption of vitamins and nutrients in an individual's intestines and colon. The method includes administering to the patient an effective amount of one of the nutritional compositions presented here to increase the absorption of nutrients such as vitamin D, zinc or calcium to help improve bone composition and function.
Another method of the present description concerns the intensification of a patient's muscle mass by increasing the absorption of nutrients in an individual's intestines and colon. The method includes administration to an individual who desires such enhanced muscle mass and greater absorption of an effective amount of one of the nutritional compositions presented here in order to specifically increase the absorption of nutrients such as folates, vitamin D, magnesium or B12 in the individual to help muscle growth, prevent muscle mass reduction or improve muscle mass recovery.
An individual's metabolism can be improved by administering an effective amount of one of the nutritional compositions presented here. This allows the individual to improve the absorption of micronutrients, improve the bioavailability of such micronutrients, or provide greater caloric absorption. This can confer a number of advantages, since the individual can have a better start in the morning with such improved absorption. In addition, this can also be used to treat obesity, since the individual receiving the composition will have a fuller feeling or satiety to avoid overeating. This can also lead to a decrease in caloric intake while also
37/72 provides sustained energy so that the individual is able to participate in exercises or other activities that will burn calories after administering the composition.
The compositions are also useful in the treatment of diabetes in a patient in need of such treatment. The administration of one of the nutritional compositions presented here may reduce insulin resistance, reduce the blood glucose excursions or reduce the risk of CVD.
Exemplifying Modalities
One embodiment of the present description is a nutritional composition for administration to an individual that includes a fructo-oligosaccharide (FOS) in an amount of 35 to 44% by weight; a polysaccharide in an amount of 38% to 50% by weight; and inulin in an amount of 12 to 24% by weight. FOS and polysaccharide can be present in a weight ratio of 62:38 to 38:62, and FOS and inulin can be present in a weight ratio of 82:18 to 58:42. In an additional embodiment, the FOS is 40 to 42% by weight. In yet another embodiment, the FOS is about 41% by weight. In another additional embodiment, the polysaccharide is AG. In an additional embodiment, the polysaccharide is 40 to 50% by weight. In yet another embodiment, the polysaccharide is about 41% by weight. In an additional embodiment, AG is 40 to 42% by weight. In another additional embodiment, AG is about 41% by weight. In an additional embodiment, inulin is 15 to 21% by weight. In yet another additional embodiment, inulin is 18% by weight. In an additional modality, the nutritional composition comprises: (FOS) in an amount of 40 to 42% by weight; AG in an amount of 40% to 42% by weight; and inulin in an amount of 15 to 21 by weight. In an additional embodiment, the nutritional composition comprises: (FOS) in an amount of 41% by weight; AG in an amount of 41% by weight; and inulin in an amount of 18% by weight. In another additional modality, FOS and polysaccharide are present in a weight ratio of 55:45 to 45:55. In yet another additional embodiment, FOS and po38 / 72 lysaccharide are present in a weight ratio of about 1: 1. In an additional modality, FOS and inulin are present in a weight ratio of 76:24 to 64:36. In an additional modality, FOS and inulin are present in a 7: 3 weight ratio. In another additional embodiment, the polysaccharide is an arabinogalactan and the FOS is present in an amount between 3 and 5.5 g / l, arabinogalactan is present in an amount of 3-5.5 g / l and inulin is present in an 1-2.5 g / l. In another additional embodiment, the nutritional composition additionally comprises up to 10 g / l of (PHGG). In yet another modality, arabinogalactan is AG and each of the FOS and AG is present in an amount of 4.12 g / l, inulin is present in an amount of 1.76 g / l and PHGG is present in an amount of 7 g / l. In an additional modality, arabinogalactan is AG and each of the FOS and AG is present in an amount of 4.12 g / l, inulin is present in an amount of 1.76 g / l and PHGG is present in an quantity of 5 g / l. In another additional modality, arabinogalactan is AG and each of the FOS and AG is present in an amount of 4.12 g / l, inulin is present in an amount of 1.76 g / l and PHGG is present in an amount of 2.6 g / l. In yet another embodiment, the (FOS) in an amount of 35% by weight; a polysaccharide in an amount of 50% by weight; and inulin in an amount of 15% by weight. In an additional embodiment, the (FOS) in an amount of 35% by weight; AG in an amount of 50% by weight; and inulin in an amount of 15% by weight.
Again, it should be noted that although guar gum, chemically speaking, is a polysaccharide, and although a PHGG may still be, at least in part, a polysaccharide, the polysaccharide included in the currently claimed nutritional composition does not include PHGG. Instead, PHGG can be added in addition to the polysaccharide in such a way that, for example, AG and PHGG are not added together to obtain 38-50% polysaccharide. Instead, PHGG can be added to nutritional compositions in addition to the 38-50% polysaccharide.
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In one embodiment, the nutritional composition further comprises at least one insoluble fiber in an amount effective to enhance the digestive function in the individual, wherein at least one insoluble fiber is a soy fiber, an outer pea fiber, or a combination thereof . In an additional embodiment of the nutritional composition, soluble fiber and insoluble fiber are present at a ratio between 1.5: 1 and 1: 1.5, and FOS and AG are present in a total amount between 2.5 and 3 , 5 g / l, inulin is present in an amount between 1.25 and 1.75 g / l, and each of the soy fiber and the outer fiber of the pea is present in an amount between 3.25 and 4 , 25 g / l. In an additional embodiment of the nutritional composition, soluble fiber and insoluble fiber are present at a ratio of 1.25: 1 and 1: 1.25. In another additional form of the nutritional composition, soluble fiber and insoluble fiber are present at a ratio of 1: 1. In yet another form of nutritional composition, FOS and AG are present in a total amount of about 3 g / l. In an additional form of the nutritional composition, inulin is present in an amount of about 1.5 g / l. In yet another modality of nutritional composition, each of the soy fiber and the outer fiber of the pea is present in an amount of about 3.75 g / i.
In one embodiment, the nutritional composition further comprises antioxidants.
In one embodiment, the nutritional composition additionally comprises fish oils or non-fish oils, such as algae.
In one embodiment, the nutritional composition additionally comprises DHA, EPA, or combinations thereof.
In one embodiment, the nutritional composition additionally comprises vitamins, minerals, or combinations thereof.
In one embodiment, the nutritional composition additionally comprises phytonutrients.
In one embodiment, the nutritional composition additionally comprises proteins.
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In one embodiment, the nutritional composition additionally comprises fats.
In one embodiment, the nutritional composition further comprises probiotics.
In one embodiment, the nutritional composition is a dry powder formulation. In another embodiment, the nutritional composition is obtained by preparing one of the compositions as a liquid and by drying the liquid composition by one of the processes known in the art, including spray drying, freeze drying or other drying techniques for produce a dry powder composition. In another additional embodiment, the nutrient components or compositions are added to the liquid prior to drying to confer greater nutritional benefits to the powder composition. In a further embodiment, a nutritional composition is obtained by reconstituting the dry powder formulations of claims 35 to 37 by combining the formulation with a liquid.
In one embodiment, the nutritional composition is a complete nutritional complex. In one embodiment, the nutritional composition is an incomplete nutritional complex.
In one embodiment, the nutritional composition is used in a method of promoting the balance of gut microbiota and health. The method includes an effective amount of the nutritional composition for an individual who can benefit from such treatment.
In one embodiment, the nutritional composition is used in a method to improve the patient's tolerance of the various medical treatments that lead to disorders of the gastrointestinal tract, and such treatments include radiotherapy, chemotherapy, gastrointestinal surgery, anesthesia, administration of antibiotics, analgesic drugs or treatments for diarrhea. The method includes administering to such patients an effective amount of the nutritional composition.
In one embodiment, the nutritional composition is used in a method to provide benefits such as better growth for children. The method includes administering to such children an amount
41/72 effective nutritional composition.
In one embodiment, the nutritional composition is used in a method of reducing the length of hospital stay for patients. The method includes administering an effective amount of the nutritional composition to a hospital patient, to allow such patients to achieve acceptable levels of nutrition and feeding goals with greater tolerance for such formulations to increase their compliance with feeding requirements, and decreased complications such as diarrhea or constipation in order to improve the patient's condition and thereby reduce the length of hospital stay. In an additional modality, the patient is adult and elderly.
In one embodiment, the nutritional composition is used in a method of minimizing the negative evolution of intestinal microbiotics in an elderly individual due to old age by administering an effective amount of the nutritional composition to such individuals to allow such individuals to maintain healthy levels of powder microbiotas longer despite their growing age. In an additional modality, the method comprises the reduction of Clostridium. In another embodiment, the method comprises increasing Bifidobacteria.
In one embodiment, the nutritional composition is used in a method to increase butyrate production in a patient's colon. The method includes administering an effective amount of the nutritional composition to the patient to increase butyrate production compared to formulations that do not contain AG to produce cell proliferation in the colon and to lower the pH of the colon to inhibit the growth of the colon. pathogenic bacteria. In an additional modality, the method leads to anti-inflammatory benefits, which helps to protect the patient's intestinal barrier. In an additional modality, the method leads to an increase in mineral absorption. In an additional modality, the method leads to a normalization of gastrointestinal transit time. In an additional modality, the method leads to a reduction in diarrhea. In an additional modality, the method leads to a decrease in constipation.
In one embodiment, the nutritional composition is used in a whole method to enhance an individual's immune system. The method includes, for an individual who wishes to stimulate their immune system, an effective amount of the nutritional composition. In an additional modality, the stimulated immune system decreases pathogenic microorganisms, such as Clostridium difficile. In an additional embodiment, the stimulated immune system comprises the improved function of T cells. In an additional embodiment, the stimulated immune system comprises the improved function of GALT. In an additional embodiment, the stimulated immune system comprises the enhanced production of slgA. In an additional modality, the stimulated immune system increases the individual's ability to resist disease.
In one embodiment, the nutritional composition is used in a method to improve tolerance to organ transplantation by administering to an individual who receives a transplant an effective amount of the nutrient complex to provide specific colonizations that confer unique downward regulation. In an additional modality, upward regulation leads to a decrease in inflammatory cytokine which leads to an increase in lean body mass. In an additional modality, upward regulation leads to increased insulin release through GLP-1 and GLP-2. In an additional modality, upward regulation leads to less TH1 / TH2 imbalance.
In one embodiment, the nutritional composition is used in a method to improve bone growth or prevent bone degradation in a patient in need of it by increasing the absorption of vitamins and nutrients in an individual's intestines and colon. The method includes administering to the patient an effective amount of one of the nutritional compositions presented here to increase the absorption of nutrients such as vitamin D, zinc or calcium to help improve bone composition and function.
Another method of the present description concerns the intensification of a patient's muscle mass by increasing the absorption of nutrients in an individual's intestines and colon. The method includes
43/72 administration to an individual who desires such increased muscle mass and increase the absorption of an effective amount of one of the nutritional compositions presented here in order to specifically increase the absorption of nutrients such as calcium, vitamin D, folates, magnesium or B12 , in the individual to help muscle growth, prevent muscle mass reduction or improve muscle mass recovery.
In one embodiment, the nutritional composition is used in a method to increase the absorption of vitamins and nutrients in an individual's intestines and colon. The method includes administering to an individual who desires such increased adsorption of an effective amount of the nutritional composition in order to specifically increase the absorption of vitamins or calcium and other minerals or vitamins and minerals in the individual. In an additional embodiment, the vitamins are vitamin D, folates, B12, etc. In an additional embodiment, the minerals are at least magnesium or calcium. In an additional modality, the method helps in muscle growth. In an additional modality, the method prevents the reduction of muscle mass. In an additional modality, the method improves the recovery of muscle mass from illness or injury.
In one embodiment, the nutritional composition is used in a method to improve an individual's metabolism. The method includes administering to an individual who desires such improved metabolism an effective amount of the nutritional composition. In an additional modality, the method intensifies the absorption of micronutrients. In an additional modality, the method improves the bioavailability of micronutrients. In an additional modality, the method provides greater caloric absorption. In an additional modality, the method provides greater caloric absorption so that the individual can have a better start in the morning. In an additional modality, the method gives a feeling of satiety. In an additional modality, the method gives a feeling of satiety to avoid overeating. In an additional modality, the method gives a feeling of satiety to decrease caloric intake. In an additional modality, the method gives a feeling of satiety to treat
44/72 obesity. In an additional embodiment, the method provides sustained energy after such administration.
In one embodiment, the nutritional composition is used in a method of treating diabetes in a patient who can benefit from such treatment. The method includes administering to such a patient an effective amount of the nutritional composition. In an additional modality, the method decreases insulin resistance. In an additional modality, the method decreases blood glucose excursions. In an additional modality, the method decreases the risk of CVD.
One embodiment of the present description includes a use of a polysaccharide, such as a gum, in a nutritional composition that includes FOS and inulin for administration to an individual to provide nutrition to the individual, wherein the polysaccharide is present in an effective amount. to confer a greater tolerance to such nutritional compositions when administered to the individual, in which the polysaccharide, FOS and inulin are present in the amounts presented here. In an additional embodiment, the polysaccharide is AG.
One embodiment of the present description includes a use of a polysaccharide, such as a gum, for the preparation of a nutritional composition to promote intestinal microbiotic balance and health in an individual, wherein the nutritional composition also includes an FOS and an inulin, in the quantities presented here. In an additional embodiment, the polysaccharide is AG.
In one embodiment, the nutritional composition is used in a method of using an effective amount of the nutritional composition for long-term administration.
In one embodiment, the nutritional composition is used in a method of using an effective amount of the nutrient for short-term administration.
In one embodiment, the nutritional composition is used in a method of using an effective amount of the nutritional composition for administration with tube feeding.
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In one embodiment, the nutritional composition is used in a method to modulate the hormones produced by the gastrointestinal tract or regulated by the gastrointestinal tract, which comprises administration to an individual who can benefit from it from an effective amount of the nutritional composition. In an additional modality, inflammatory hormones are decreased in the individual. In an additional modality, an individual's sense of well-being is increased. In an additional embodiment, serotonin is increased. In an additional embodiment, serotonin leads to improved sleep patterns in the individual. In an additional embodiment, serotonin leads to improved sleep quality for the individual. In an additional embodiment, serotonin leads to a decrease in depression. In an additional modality, serotonin leads to a normalization of appetite. In an additional modality, cognition is improved.
In one embodiment, the nutritional composition is used in a method to improve the bacterial balance in a pediatric patient by administering it to an individual who can benefit from an effective amount of the nutritional composition in which there is a decreased TH1 / TH2 imbalance , in which the TH1 / TH2 imbalance is a favored factor of the TH2 subset. In an additional embodiment, the decreased TH1 / TH2 imbalance leads to a decreased incidence of allergies. In an additional embodiment, the decreased TH1 / TH2 imbalance leads to a decreased incidence of atopic dermatitis. In an additional embodiment, the decreased TH1 / TH2 imbalance leads to a decreased incidence of asthma. In an additional embodiment, the decreased TH1 / TH2 imbalance leads to a decreased incidence of food allergies. In an additional embodiment, the decreased TH1 / TH2 imbalance leads to a decreased incidence of otitis. In an additional embodiment, the decreased TH1 / TH2 imbalance leads to a decreased incidence of viral infections. In an additional embodiment, the decreased TH1 / TH2 imbalance leads to a decreased incidence of autoimmune diseases. In an additional modality, the decreased TH1 / TH2 imbalance leads to an incidence
46/72 decreased allergic rhinitis.
In one embodiment, the nutritional composition is used in a method to provide nutrition to a patient with a kidney disorder. The method includes administering to such a patient an effective amount of the nutritional composition. In an additional embodiment, the patient has kidney failure. In an additional modality, the patient is submitted to dialysis treatments.
In one embodiment, the nutritional composition is used in a method for managing at least one inflammatory condition by administering to an individual patient an effective amount of the nutritional composition. In an additional embodiment, the inflammatory condition is the prevention of an inflammatory condition. In an additional embodiment, the inflammatory condition is a gastrointestinal inflammation. In an additional embodiment, the inflammatory condition is inflammatory bowel disease (IBD).
In one embodiment, the nutritional composition is used in a method that leads to a decrease in health care expense costs. In an additional modality, the decrease in the costs of health care expenses is due to the shorter period of stay in a hospital. In an additional modality, the decrease in health care costs is due to the shorter period of stay in a nursing home facility. In an additional modality, the decrease in the costs of health care expenses is due to the decrease in complications. In an additional modality, the decrease in health care expenditure costs is due to the lower incidence of diarrhea. In a further modality, the decrease in health care expenditure costs is due to the lower incidence of constipation. In an additional modality, the decrease in the costs of health care expenses is due to the lower incidence of diverticulitis.
The above description of various aspects of the present description has been presented for purposes of illustration and description. It is not intended that
47/72 it is exhaustive or limiting the present description to the precise form presented and, obviously, many modifications and variations are possible. Such modifications and variations that may be apparent to an element skilled in the art should be included within the scope of the present description as defined by the appended claims.
EXAMPLES
Example 1: Enteral formula containing pro- and prebiotics in the pediatric intensive care unit (PICU): tolerance, safe use and intestinal ecology
Background
The objective of this project was to renew a supplement with an innovative nutritional concept to increase the value proposition of the product in the area of growth and protection benefits (reinforces the child's defenses).
For this purpose the formula was enriched with a mixture of two probiotic bacteria, Lactobacillus paracasei NCC2467 (ST11) and Bifidobacterium longum NCC 3001 (Bb536), a unique combination of PREBIO1 ™: AG and DHA.
For the substantiation of tolerance / safety and benefit in the context of the health care environment, a clinical trial was initiated:
Clinical Experimentation
The clinical trial was carried out in Nakhon Ratchasima, Thailand with 94 children hospitalized in the pediatric intensive care unit (PICU) in need of mechanical ventilation and enteral feeding. The study was carried out for almost three years. The tolerance / safety analysis takes into account both the total percentage of caloric intake and the time to reach the target caloric intake while the benefit analysis assesses the composition of faecal microbiotes, including the presence of the strains NCC 2461 (ST11) and NCC 3001 (BB536).
Methods
This was a randomized controlled clinical trial
Double blind 48/72. Two products were under investigation, an experimental product and a control product.
Experimental Product (Nutren Junior)
Enteral formula with probiotics NCC2461 / NCC3001 + prebiotics (PREBIO1 ™ + AG) + DHA.
Control Product (Nutren Junior)
Isocaloric and isoprotein formula without the addition of pro- and prebiotics or DHA.
Patient results were randomized and assigned to treatment, in which all had at least one day study of the product intake. 88 patients ingested more than 3 days of enteral feeding (PP data set).
Tolerance / Safety Analysis
Percentage of total caloric intake
The total percentage of caloric intake during hospitalization was calculated by adding the total volume administered in 24 hours in relation to the days available, divided by the number of days times the weight times 70 kcal / kg / day. This was done for each individual. The total percentage of caloric intake was analyzed by the Wilcoxon degree-sum test, and the confidence intervals were calculated according to Hodges-Lehman. The summary statistics and the difference in treatment are shown in Table 2.
Table 2: Summary statistics of the total percentage of caloric intake and difference in treatment. For summary statistics, the average number and quartiles are presented, for the difference in treatment, the pseudo average and the 95% confidence interval on both sides. Everything refers to the PP data set.
Data set
New Nutren Junior Nutren Junior Δ 95% CI Medium 25% 75% Medium 25% 75% bottom higher PP 76.2 65.3 84.3 75.1 69.2 83.6 0.3 -7.1 7.9
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The two-sided 95% confidence interval ranges from -7.1% to 7.9% of total caloric intake. The lower limit of the confidence interval, 7.1%, is greater than -15%, which was defined as a significant difference. In this way, a non-inferiority between the two products was demonstrated. Moment of reaching the target caloric intake
The time to reach the target daily caloric intake is the time when the daily energy intake (DEI) goes through 100%. Since it was not expected that a child would reach exactly 100% on a given day, that time was calculated for each child by linear interpolation between the day before 100% and the day after 100% DEI was measured. Children who did not reach the daily caloric goal during the seven days of tube feeding were censored. As shown in the Kaplan Meyer graph shown in figure 1, 36% and 29% of the children did not reach the caloric goal in the test and control groups, respectively, for seven days. The average time to reach the caloric goal was 5.10 and 5.03 days in the test and control groups, respectively. The time difference was one hour, the 95% confidence interval is 29 hours to 61 hours. This also shows the non-inferiority between the two products tested.
The timing of reaching the caloric goal was also analyzed using a registration-grade test. The p-value is 0.67. The average time to reach the goal is shown by the treatment group in Table 3.
Table 3: Summary statistics of the moment to reach the caloric goal. The mean time and the 95% confidence interval for two sides are shown. It all refers to the PP data set.
n events medium 95% CI bottom higher New Nutren Junior 44 28 5.10 4.64 00 Nutren Junior 44 30 5.03 4.46 6.14
Safety was confirmed through general improvement of health status and tolerance parameters as evidence of support (abdominal distension, vomiting, frequency of evacuation / diarrhea, etc.). It was found that the use of the enteral formula containing pre- and probiotics is safe with respect to the four parameters indicated above.
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According to clinical records, patients in both groups recovered from the critical condition and were finally released from PICU within the framework of regular clinical practices (max. +/- seven days after hospitalization). In addition, no side effects related to the product were reported by the researcher during the study, supporting the safety of the tested products.
Analysis of Prebiotic Benefits
The composition of faecal microbiotes was selected as a key parameter that reflects the balance of the intestine in such a critical environment (patients being treated with antibiotics at high risk of infections). The following bacterial groups were measured: the genus Bifidobacterum, the genus Lactobacillus, the group Bacteroides / Porphiromonas / Prevotella, the family Enterobactericeae, the species Clostridium perfringens and the genus Enterococcus. The average values (Iog10) are shown in Table 4.
Table 4: Summary statistics in bacterial families (scale
Iog10), PP data set. Where n is number of individuals, n> DL number of individuals with measurements above the detection limit, p> percentage of DL of individuals with measurements above the detection limit.
n Nutoen Junior max New Nutren Junior n> DL p> DL min average n n> DL p> DL min average max Bmdobactería Baseline 40 32 80% 5.00 7.72 9.95 43 35 81% 3.00 7.01 10.11 7 days 39 28 71% 3.00 7.03 10.00 41 27 65% 3.00 7.36 9.60 14 days 36 25 69% 5.00 7.20 9.52 37 30 81% 5.00 7.76 9.78 iaefo & aáffi ' Baseline 40 38 95% 3.48 5.84 9.40 44 42 95% 3.00 5.56 8.48 7 days 39 38 97% 3.30 6.03 9.27 42 40 95% 3.48 5.86 9.95 14 days 36 35 97% 3.00 5.81 9.16 38 36 94% 4.11 656 8.85 Bademdes Baseline 40 37 92% 6.20 8.75 10.43 44 42 95% 5.00 8.57 10.28 7 days 39 38 97% 5.00 8.56 10.30 42 39 92% 5.60 8.62 10.36 14 days 36 34 94% 5.00 8.47 10.23 38 35 92% 5.00 8.86 10.11 Enterebatíeria Baseline 40 38 95% 3.48 7.92 9.70 44 40 90% 3.30 7.57 9.30 7 days 39 36 92% 4.45 7.62 9.48 42 39 92% 3.00 6.61 9.95 14 days 36 34 94% 3.00 7.46 8.85 38 38 100% 3.00 7.08 9.30 Ciostridium perfringens Baseline 40 13 32% 3.48 5.50 7.50 44 14 31% 3.00 4.58 5.95 7 days 39 7 17% 3.48 4.69 7.85 42 4 9% 3.48 3.73 3.95 14 days 36 11 30% 3.00 4.57 7.48 38 11 28% 3.00 4.47 6.15 Enterococã Baseline 40 37 92% 3.70 6.72 9.29 44 41 93% 3.00 625 9.23 7 days 39 34 87% 3.48 7.49 9.45 42 38 90% 3.00 7.08 9.67 14 days 36 32 88% 4.43 7.30 9.33 38 36 94% 3.00 7.22 9.82
Within the genus Bifídobacterium, the strain Bifidobacterium lon51 / 72 gum NCC 3001 was identified by means of specific PCR, and within the genus Lactobacilli, the strain Lactobacillus paracasei NCC 2461 was also identified by means of specific PCR. The strains NCC 3001 and NCC 2461 were identified in 18% to 84% of patients receiving enteral formula with pre- and probiotics during their stay at PICU.
Differences in change counts from the Bifidobacteria baseline between the control and test groups were 0.17 Iog10 CFU / mg and 1.43 Iog10 CFU / mg at seven days and fourteen days, respectively. The difference in fourteen days was statistically significant, p = 0.013. The increase in Bifidobacteria should not only be attributed to the Bifidobacterium strain contained in the test product, but may also reflect an additional bifidogenic effect of the prebiotic mixture (PREBIO1 ™ + AG) added to the product. The differences for Lactobacilli follow the same trend (not significant) with a 0.75 level higher record in the test group compared to the control at the end of the supplementation period (day 14). The mean values of Bacteroides and Enterococci levels were kept unchanged in both treatment groups.
In both groups, there was a progressive decline in Clostridium perfringens levels over the period of hospitalization (PICU). The same observation was made for Enterobacteria. Although not statistically significant, the effect for the latter was more pronounced (decline of about 1 long in seven days) with feeding with the test product. Conclusions
The results show that enteral feeding with / a supplement comprising PREBIO1 ™ and AG is better tolerated than Nutren Junior already on the market that comprises only PREBIO1 ™. In addition, in comparison with Nutren Junior, the new Nutren Junior is more effective in promoting not only the reduction of bacterial groups that comprise pathogens known among its members (Enterobacteria, Clostridia), but also in increasing the microbial groups of reputable beneficial effects ( Bifidobacteria), thereby positively balancing the microbiota composition in sick children.
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Example 2: Enteral formula containing pro- and prebiotics in PICU: tolerance, safe use and intestinal ecology
Background
Malnutrition in children hospitalized in conjunction with global disorders of intestinal microbiota are the conditions that favor both episodes of acute diarrhea and also the long-term refuge of intestinal pathogens that are sources of nosocomial infections.
Goals
The aim of the present study is to demonstrate the tolerance of an enteral formula containing pro- and prebiotics, its safe use in PICU and its ability to support the intestinal bacterial flora.
Design / Methods PICU patients between 1 and 3 years of age in need of mechanical ventilation and enteral feeding were randomized to receive a test formula containing probiotics, prebiotics and DHA, or an isocaloric control and isoprotein formula. The patients remained in the PICU for seven days and were further examined on the 14th. The preliminary objective was to assess the tolerance measured by progression to the caloric target and the secondary objectives were to determine the safe use and improvement of intestinal microbiotics.
Results
The total caloric intake was no different between the two formulations. The average time to reach the caloric goal was 5.1 in the test group and 5.03 in the control group (p = 0.67). With regard to safety, patients in both groups recovered from the critical condition and were released from PICU within the timeframe of current clinical practice. As supporting evidence for the safe use of enteral formulas, no difference in bloating, vomiting and frequency of bowel movement / diarrhea was observed between the two products tested. In addition, no side effects were observed in either group.
Bifidobacteria decreased in the control group, while they increased in the test group, reaching a difference in es53 / 72 tactical significance on day 14 (P = 0.013). A similar trend was observed for Lactobacilli with 0.75 higher levels of registration in the test versus control (NS) group. The Lactobacillus paracasei NCC2461 probiotic strain used in the study was recovered from feces in 84% of cases. The Bifidobacterium longum NCC3001 strain, the second probiotic strain, was recovered in only 18% of cases. Bacteroides and Enterococci remained unchanged. A progressive decline in Ctostridium perfringens during hospitalization was observed in both groups. Although Enterobacteria levels remained unchanged in the control group, their levels decreased by 1 log in the test group while staying at PICU.
Conclusions
The use of formula supplemented with pro- and prebiotics does not alter the tolerance of enteral nutrition in PICU. In addition, such a formula is safe and promotes a positive balance of the composition of the microbiota in critically ill children.
Example 3: In vitro evaluation of a prebiotic mixture using the Human Intestinal Microbial Ecosystem Simulator (SHIME).
An in vitro evaluation of two prebiotic mixtures was performed in which a simulator of the human gastrointestinal tract (model TWINSHIME) was used to evaluate the prebiotic activity of a prebiotic mixture of the present nutritional compositions (indicated as Mixture ¹ *) for application as both a oral nutritional supplement (ONS) and in a tube feeding formulation (TF). The focus of the assessment was to assess the impact of partial replacement of FOS and inulin with AG in a unique fiber blend (referred to as Mixture ¹ ) on microbial fermentation characteristics in an ONS strategy.
The in vitro approaches to study the microbiologic processes of the gastrointestinal and intestinal tracts offer an excellent experimental configuration for studying the possible prebiotic properties of selected food ingredients. The application of well-designed continuous models allows the in-depth study of the biological activity of selected molecules in the intestine under representative environmental conditions. Besides that,
54/72 Recent advances in in vitro modeling also allow combining the study of interactions of host-bacteria, such as mucosal adherence and interaction with the immune system, with the continuous model, thereby promoting increased scientific production and relevance commercial.
The two prebiotic mixtures that were used in this study included 30% fat, 25% protein and 50% carbohydrates. The mixtures differed in the composition of the carbohydrate. Misturai (SHIME1) contained FOS and inulin in a ratio of 70% to 30%. Misturai + (SHIME2) contained 41% FOS, 41% acacia gum and 18% inulin. The products were available in portions containing 3.3 g of fiber. A total amount corresponding to two portions of the mixtures per day was administered to the respective SHIME model. The mixtures were administered to the models as part of the liquid nutrient medium that enters the stomach compartments three times a day, resulting in the administration of 2.2 g of fiber three times a day.
Simulator of the Human Intestinal Microbial Ecosystem
To study the potential prebiotic properties of the selected products in detail using an in vitro configuration, a continuous model was used, which allows cultivating the complex intestinal microbial ecosystem for a long period and under representative conditions. In addition, since previous in vivo and in vitro studies have shown that the evaluation of prebiotic properties can only be carried out after two to three weeks of continuous administration of the compound, the model should allow the simulation of repeated intake of prebiotics. Therefore, the dynamic SHIME simulator of the human gastrointestinal tract was used to assess the effectiveness of prebiotic treatment.
The reactor configuration was adapted from SHIME, representing the adult human gastrointestinal tract (GIT), as described by Molly et al. See Molly, et al., Development of a 5-step multichamber reactor as a simulation of the human intestinal microbial ecosystem, Applied Microbiology and Biotechnology 39: 254-258 (1993). O
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SHIME consists of a succession of five reactors that simulate the different parts of the human gastrointestinal tract. See, for example, figure 2.
The first two reactors are of the principle of filling and extracting to simulate different stages in the absorption and digestion of food, with peristaltic pumps adding a defined amount of SHIME feed (140 ml 3x / day) and pancreatic and bile liquid (60 ml 3x / day), respectively, to the stomach (V1) and duodenum (V2) compartments and emptying the respective reactors after specific intervals. The last three compartments are continuously agitated reactors with constant volume and pH control. The retention time and pH of the different vessels are chosen in order to resemble in vivo conditions in the different parts of the gastrointestinal tract. The total residence time of the last three vessels, simulating the large intestine, is 72 hours. With inoculation with fecal microbiotes, these reactors simulate the ascending (V3), transverse (V4) and descending (V5) colon. The preparation of the inoculum, the retention time, the pH, the temperature adjustments and the feed composition of the reactor were previously described by Possemiers et al. See Possemiers et al., PCR-DGGE-based quantification of stability of the microbial community in a simulator of the human intestinal microbial ecosystem, FAMS Microbiology Ecology 49: 495-507 (2004).
SHIME has been used extensively for more than 15 years for scientific and industrial projects and has been validated with in vivo parameters. With the stabilization of the microbial community in different regions of the colon, a representative microbial community is established in the three compartments of the colon, which differs in composition and also functionally in different regions of the colon.
For these experiments, a TWINSHIME configuration was used when operating two systems in parallel at the same time (SHIME1 = Mix ¹ ; SHIME2 = Mix ¹ *). The identical environmental conditions for both systems were obtained by the identical control of pH and temperature and by using the two column pumps for the transfer of liquid between the reactors.
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The SHIME experiment consisted of three stages. The first stage was a starting stage. After inoculating the colon reactors with an appropriate fecal sample (elderly donor with a low concentration of bifidobacteria), a two-week starting period allowed the microbial community to differentiate in different reactors depending on local environmental conditions. The second stage was a control period that was the real start of the experiment, in which the standard SHIME feed was dosed to the model for a period of 14 days. The basal medium was composed as follows: arabinogalactan (1 g / i), pectin (2 g / l), xylan (1 g / l), starch (3 g / l), glucose (0.4 g / l) , yeast extract (3 g / l), peptone (1 g / l), mucin (4 g / l), cysteine (0.5 g / l). The analysis of the samples in this period allowed to determine the composition and the microbial activity of the baseline community in the different reactors, which were used as a control to compare with the results of the prebiotic treatment. The final third stage was a treatment period. During this three-week period, the SHIME reactor was operated under nominal conditions, but with a modified diet containing a smaller amount of starch in the medium compared to that of the baseline period (1 g / l). This allowed us to locate the effect of the two products on top of a typical diet in the elderly (a diet that contains low nutrients). In parallel, the SHIME diet was supplemented with prebiotics (which corresponds to two portions of the mixtures per day).
Results
A number of microbial parameters were monitored throughout the experiment including, for example, short-chain fatty acids, ammonium, lactate analysis, gas analysis, intestinal pH and sample collection.
Short-chain fatty acids (SCFAs '')
SCFAs are typical end products mainly of saccharolytic fermentation by intestinal bacteria and SCFA profiles consist mainly of acetate, propionate and butyrate with small amounts of other acids such as isobutyric, valeric, isovaleric and caprylic acids. While acetate can be absorbed from the intestine and used as an energy substrate by the host, butyrate acts as a major energy substrate for the intestinal epithelium and has shown protective effects against inflammation and colon cancer. Finally, propionate has a similar local activity in the intestine compared to butyrate, however, it is also transported to the liver where it has been shown to have positive cholesterol-lowering effects and effects on glycemic control. For this reason, butyrate and propionate are considered to be more beneficial to the health of the host compared to acetate, and the modulation of microbial fermentation profiles in the intestine for increased butyrate and / or propionate production is considered beneficial.
With respect to SCFAs, samples were collected three times a week from all compartments of the colon to analyze the concentration of acetic acid, propionic acid, isobutyric acid, butyric acid, isovaleric acid, valeric acid, isocaproic acid and capróic acid. In Figures 3A-F, data are presented as total production of SCFA, acetate, propionate and butyrate per week of the TWINSHIME experiment. As mentioned above, prebiotic properties are assessed by a relative increase in propionate and / or butyrate in total SCFA production. The data are also summarized by experimental period and by colon compartment in Tables 5 and 6.
Since acetate (A), propionate (P) and butyrate (B) are the main SCFA produced by intestinal bacteria, the data can also be expressed as an A / P / B ratio. To do this, the production of each fatty acid is presented as the ratio of the concentration of each individual fatty acid to the sum of the concentrations of the three fatty acids. In this experiment, the prebiotic effects of a treatment, as determined by a relative increase in propionate and / or butyrate production, were assessed by an increase in P and / or B and a decrease in A in the A / P / B ratio . The A / P / B ratios are presented, per week of experiment, in figures 4A-F.
Based on the considerations made above, both products provided clear indications of prebiotic activity. Both treatments
58/72 induce an increase in the total concentration of SCFA in all vessels of the colon, indicating that both products fermented well in the GIT. In addition, both products induce a higher concentration of propionate and butyrate and are able to move the Acetate-Butyrate-Propionate ratio to a healthier composition. When assessing the statistical differences in the production of SCFA between control and treatment, clear changes typically only begin from the second week of treatment. This was also observed in this experiment and refers to the adaptation period that the bacteria need to adapt to the new nutritional environment. This leads to gradual changes in SCFA profiles during the first week of treatment (high standard deviation) and often results in a lack of statistical significance when the average SCFA concentrations in the first week of treatment are compared with those in the control period. With the adaptation to fiber mixtures (from week 2 of the treatment period), clear significant differences were observed in the SCFA profiles.
In figures 5A-E, a comparison between the two SHIME systems is presented, allowing to compare the prebiotic potential of the original mixture and the adapted fiber mixture. The comparison was performed separately for each week of the experiment. Within each week, the concentrations of total SCFA, acetate, propionate and butyrate in each colon compartment were compared using one-way ANOVA, and the individual means were compared using the Tukey test.
Based on the two SHIME runs, it was found that no statistical difference in SCFA production was observed in any of the colon compartments during the control period (ctr), indicating that the starting point for the two different treatments was similar. It was also found that no statistically significant difference was observed in the effect of the two products during the first week of the treatment period (tr). This is believed to be related to the adaptation period for microbiota in the gut to adapt their metabolism to the test compounds administered. In addition, from the second se59 / 72 mana of treatment, statistical differences occurred. This indicates that both products had a different fermentation profile, resulting in specific profiles of SCFA production.
The present experiment also demonstrates that the partial replacement of FOS and inulin by the form of acacia induces differences in the bacterial fermentation profiles. First, the butyrogenic effect of Mixture ¹ was higher than that of Mixture ¹⁺ , whereas Mixture ¹⁺ showed a higher concentration of propionate (even though it was not always supported by statistics). Second, these findings show that although both mixtures have a very positive effect in terms of SCFA production, the specific fermentation profile depended on the specific composition of the mixtures.
Ammonium
Since ammonium production is mainly the result of protein degradation and is associated with direct and indirect harmful health effects, a reduction in ammonium production should therefore be considered to be beneficial. During this experiment, samples were collected three times a week from all compartments of the colon. The analysis of ammonium concentrations in different regions of the colon throughout the course of the experiment is shown in figures 6A and 6B. As is clearly indicated, both products induce a decrease in ammonium production during the treatment period.
In addition, ammonium concentrations in SHIME can also be seen as a marker for the limited substrate availability for bacteria during the treatment period. If certain bacteria cannot use the products administered as efficiently as they can use starch as an energy source, these bacteria can move on to a more proteolytic metabolism, which results in higher concentrations of ammonium. The observed decrease in ammonium concentrations, therefore, is also a sign of high fermentability of both mixtures.
Finally, no statistical difference was observed between
60/72 the two runs of SHIME, indicating that the partial replacement of FOS and inulin by acacia gum did not affect the decrease in ammonium production, and that Mixture ¹⁴ was also well fermented, resulting in greater saccharolytic fermentation in the colon.
Lactate Analysis
The human intestine is home to bacteria that produce lactate and bacteria that use lactate. Lactate is produced by lactic acid bacteria and lowers the pH of the environment, also acting as a microbicidal agent. It can also be quickly converted to acetate, butyrate and propionate by other microorganisms. For the purposes of the present study, samples were collected three times a week from all compartments of the colon. The analysis of lactate concentrations in different regions of the colon throughout the course of the experiment is shown in figures 7A and 7B.
The administration of both mixtures significantly increased the remaining lactate concentrations in the ascending colon. The comparison of both SHIME runs shows that partial replacement of inulin and FOS decreases the remaining lactate concentrations. This may be related to a faster and more intense fermentation of inulin and FOS in the ascending colon compared to acacia gum. The highest concentrations of lactate in SHIME 1 are also consistent with the highest concentrations of butyrate, since lactate is an important precursor to butyrate.
Variation of pH online in TWINSHIME
To make sure that ideal environmental conditions are maintained, the pH in a SHIME system is controlled by pH controllers in the following ranges: (i) 5.6-5.8 (ascending colon, AC), (ii) 6.2 -6.4 (transverse colon, CT), and (iii) 6.6-6.8 (descending colon, CD). However, with the microbial community stabilizing in the different reactors (starting two weeks after inoculation), the microbial community can self-regulate and acid-base consumption is usually low. During a treatment, however, when the bacteria adapt to the test product and
61/72 produce, for example, increased amounts of SCFA, the environment in the reactors can become acidified, which results in additional pH control through more basic administration to the respective reactors. In this context, the degree of acidification during the experiment can be used as a measure of the intensity of the bacterial metabolism of the prebiotic mixture.
The analysis of acid and base consumption in different regions of the colon throughout the course of the experiment is shown in figure 8. As shown in figure 8, the administration of both mixtures induces acidification of the simulated colon reactors, indicative of increased production of SCFA and a healthier intestinal environment. However, since this acidification was limited to the ascending colon for Mixture ¹ , acidification occurred throughout the simulated colon with the administration of Mixture ¹⁴ / This shows that the partial replacement of FOS and inulin with acacia gum changes the intestinal fermentation profile of an intensified fermentation in the proximal colon for a more gradual fermentation in the complete colon.
With regard to the pH profile in TC1 and DC1, it was expected to obtain similar pH profiles. No immediate explanation is available for the observed difference. However, it is believed that the difference may be related to differences in the pH balance capacity of the two colon compartments.
Gas production and pH variation in batch experiments
The assessment of total gas production is an important aspect related to the potential issues of tolerance for the two mixtures in this study. However, total measurements of in-line gas production are difficult in continuous gut models due to the continuous flow of gases in and out. For this reason, the assessment of total gas production and the measurement of changes in CO2 concentration were performed in batch configurations. With respect to gas analysis, an additional batch test was performed to measure the estimate of total gas production and the composition of the gas phase under simulated colon conditions.
The typical short-term selection test (figure 9), consists of
62/72 in the sequential (triplicate) incubation of a representative dose of the selected compound under simulated conditions for (i) the stomach (pH 2, pepsin), (ii) the small intestine: addition of pancreatic enzymes and bile salts, and (iii) the large intestine with a representative bacterial inoculum in the basal environment. This bacterial inoculum was derived from a microbial community already adapted in vitro from the ascending colon compartment in the SHIME system.
The experiment was designed in such a way that the residence times typical of food products in the gastrointestinal tract are maintained. The sampling scheme is reported in figure 10. The analysis of total gas production and composition - according to the scheme reported in figure 10 - is presented in figures 11A and 11B.
Gas production typically follows a Gaussian pattern. Although it appears that a huge jump occurred between 6 and 24 hours, which would be inconsistent with such a pattern, this is only due to the fact that no sample could be collected between 6 and 24 hours. Since the main fraction of the administered fibers is fermented between 6 and 24 hours, a large apparent peak in gas production was observed in 24 hours. The comparison of both SHIME models shows that the fermentation of Mixture ¹ * induces less gas production compared to the original Mixture ¹ even if this difference between the two products after 24 hours is not statistically significant.
CO ₂ production (normally between 5 and 30% of the total gas in the intestine according to Babb, RR, Intestinal Gas (Medical Information), West J. Med. 127: 362-363 (1977)) confirmed that Mixture ¹ * fermented more slowly (fermentation still occurs between 24 and 48 hours). This also confirms previous findings: the partial replacement of FOS and inulin with acacia gum changes the intestinal fermentation profile in a more gradual fermentation.
As already indicated above, the degree of acidification at the end of the experiment is a measure of the intensity of the bacterial metabolism of the potential prebiotic. The pH of the medium in batch incubations, therefore, was determined at the beginning and at the end of the experiment to confirm the results of 63/72 of those obtained with the measurement in line (figure 12). The pH in the batch experiment again confirms that Mixture ¹ fermented more quickly than Mixture ¹⁺ .
Analysis of the composition of the microbial community
Samples were collected once a week from each of the TWINSHIME colon compartments to assess the effect of treatment on the composition of the luminal microbial community through the quantitative polymerase chain reaction (qPCR) and to analyze the microbial community associated with the mucosa. by counting plaques.
Composition of the luminal microbial community
The qPCR was used to monitor the total of bacteria, bifidobacteria, lactobacilli, firmicutes and bacteroidetes. QPCR is a molecular technique that is based on the amplification of specific bacterial sequences (165 rRNA genes), combined with the quantification of the number of these specific sequences in the microbial ecosystem at different points in time. Due to the fact that this technique is not dependent on the (lack of) culture capacity of bacteria, the data generated with this method offer a more reliable overview of the quantitative effects on the microbial community, due to prebiotic treatment.
The administration of both mixtures resulted in a clear increase in lactobacilli in all colon compartments and a significant increase in Bifidobacteria in the ascending and transverse colon. Mixture ^14- also induces a small but significant increase in Bifidobacteria in the descending colon. Above this, the administration of both mixtures increased the counts of the dominant bacterial populations (the total bacteria and Firmicutes). Blend ^1-1- also induces an increase in Bacteroidetes in the descending colon.
Firmicutes and Bacteroidetes are the two most dominant bacterial branches in the intestine. Bacteroidetes are considered as very important saccharolytic fermentation bacteria, since a large part of the proteins encoded by Bacteroidetes starts to decompose polysaccharides and to metabolize their sugars. Some species that belong to
64/72 this group are also associated with the production of propionate. The increased concentration of Bacteroidetes in the descending colon with the administration of Mixture ^14- , therefore, is an additional confirmation of the more gradual fermentation of acacia gum, leading to greater saccharolytic fermentation in the distal colon.
Firmicutes are users of the metabolic intermediates produced by the metabolism of Bacteroidetes. They include Lactobacilli and Clostridia. The latter are often considered negative for health, since specific clostridia are well-known pathogens. In addition, clostridia also includes several of the most important producers of butyrate, a bacterial metabolite that is considered to be a key health-beneficial compound.
Figures 13A-B through figures 17A-B show the qPCR data for each bacterial group presented per experimental week in each colon compartment. All figures A are related to Mixture ¹ , while all figures B are related to Mixture ¹⁺ .
In order to compare the effect of the two products on the different bacterial groups, a longitudinal statistical approach was applied that allowed to evaluate the different trends induced by the treatments. A linear groove model, which changes the position of the node in the second or third week (depending on the extent of the delay in the treatment effect - indicated with a red arrow in figures 18A, 18B, 19A, 19B and 20) was used to adjust the data and analyze the control versus the treatment period. The approach is based on the creation of a complex model and the subsequent removal, step by step, of different predictors. The difference in the values of maximum probability of two equations compared with the respective Chi Square provides the information as to whether or not the removed predictor had a statistical significance. In figures 18-20, the comparison of data from each colon vessel for the two products is shown in a diffusion chart. AC1, TC1 and DC1 always refer to Mixture ¹ ; AC2, TC2 and DC2 refer to Mixture ^14- . Weeks 1-2 represent a
65/72 control period, while weeks 3-5 represent a treatment period. Below each figure, the statistical interpretation of the trend is discussed.
As shown by figures 18A and 18B, both mixtures exhibited bifidogenic properties. Figure 18A indicates that the increase in Bifidobacteria induced by Mixture ¹ is statistically greater than by Mixture ¹⁺ . It is known from the literature that FOS and inulin can increase Bifidobacteria concentrations in the human intestine, although partial replacement by acacia gum has still increased Bifidobacteria, confirming that this substitution has no negative consequences for its prebiotic activity . In addition, as shown in figure 18B, Blend ¹ * induces a greater increase in Lactobacilli in the ascending colon compared to Blend ¹ .
Figures 19A and 19B illustrate that, based on the profiles for total bacteria, a decrease in the copy number of 165 rRNA genes can be observed for Mixture ¹ * in the ascending colon during the first week of treatment. This decrease is mainly correlated with the decrease in the dominant family of Firmicutes and Bacteroidetes in the same colon compartment. This can be explained by the fact that acacia gum is more selective and specific to ferment compared to FOS and inulin, and that bacteria need a longer time to adapt to Mixture ¹ *. Statistically, Mixture ¹ also induces higher concentrations of Firmicutes in the transverse colon.
As shown in figure 20, the amount of Bacteroidetes in the ascending colon of SHIME treated with Mixture ¹ * is statistically lower than that of Mixture ¹ during the first week of treatment, as already explained above. In the remaining part of the colon there is no difference in the effect generated by the two products.
Mucosa-associated microbial community
The interactions and specific modifications of host bacteria in this process due to a given treatment are now considered as one of the most important factors that determine the
66/72 health effects of prebiotic fibers. The human intestinal tract houses a large and complex community of microbes that is involved in maintaining human health, for example, preventing colonization by pathogens and producing important nutrients. Microorganisms are not randomly distributed throughout the intestine, and those that adhere to the intestinal wall play an important role, since they instruct mucosal immune responses and occupy a niche at the expense of potentially harmful colonizers (pathogens). Since this interaction is very difficult to study in vivo due to problems with accessibility and complexity, ProDigest and LabMET (UGent) recently developed an innovative in vitro toolbox to assess whether a prebiotic has the ability to increase adherence of health-promoting bacteria to the intestinal wall. This assay includes the investigation of the connection of the intestinal microbial community of specific regions of the colon using samples taken from the SHIME reactor at different points in time and the quantification of different bacterial groups within the fixed community (total anaerobes, Clostridia, Bifidobacteria, Lactobacilli and coliforms) faecal). The data are then processed to calculate the so-called Adherence-Related Prebiotic Index (AR-PI) (see Van den Abbeele et al., In vitro model to study the modulation of the mucin-adhered bacterial community, Appl. Microbiol. Biotechnol. ( 2009)) according to the following formula:
AR-PI =
^ClOS80 / closgo _{: C}
Table 7 shows the AR-PI calculated by taking into account the average values for the control and treatment period._
AR-PI-TREAT I B.C TC I DC SHIME 1 [ 8.7 -0.4 | -0.7 SHIME 2 | -2.7 -7.5 1 - ² · ¹
In this specific case, it is not possible to apply a particular statistic because the measurements were simple measurements and these values were compared using the same formula. It is believed that a variation of the
67/72 ± 1 index is not biologically significant. Taking Table 7 into account, Mixture ¹ (which is rapidly fermented) had no immediate effect on AR-PI in CA and no effect on the last two colon compartments. On the other hand, Mixture ¹ * had an effect throughout the colon.
In Table 8, the AR-PI is presented separately for each treatment week when comparing the single weeks of treatment with the average of the control period. For each value, additional information is also provided to explain the changes in the AR-PI with respect to the variation observed in the investigated bacterial groups.
AR-PI-TREAT J AC j TC A.D j Tri Tr2 Tr3 j Tri Tr2 Tr3 Tri Tr2 | Tr3 SHIME1 28.19 8.67 1.96! -4.99 -0.68 11.08 -0.46 0.381 -1.07 SHIME 2 1 -2.43 -0.02 -0.221 -27.49 -7.35 -6.06 -2.12 0.211 -1.40
A general consideration: within the formula, Clostridium spp.
are considered negative bacteria. However, as discussed above, among Clostridia there are several bacteria involved in SCFA metabolism. Therefore, the suggestion is to also interpret the value of AR-PI in terms of which bacterial groups are intensified and not only if the value is positive or negative.
Several conclusions can be drawn from the information represented in Table 8. First, it is evident that Mixture ¹ fermented mainly in the proximal colon and has an effect on AR-PI in the ascending colon. During the second and third weeks, the bacteria begin to adapt to the product. In addition, in the transverse colon, bacteria are positively affected by Mixture ¹ , but it takes the entire treatment period to observe this effect. Mixture ¹ did not induce any changes in the distal colon. Mixture ¹ * is probably a more balanced formulation and less easy to ferment. For this reason, it has an effect on the entire colon. The numbers are always negative and this is mainly correlated with an increase in Clostridia and a parallel decrease in Bifidobacteria.
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All of these analyzes were done using plate counts for specific groups. The luminal content was also analyzed by plate counts as part of the adherence experiment, and these data are also available. Thus, a secondary result of the analyzes is also the quantification of the luminal content of Clostridia and Coliforms. These data are reported in Table 9.
Table 9: Concentrations (CFU / ml) of Clostridia and Coliforms for tests performed when using Mixture ¹ (SHIME 1) and Mixture ^14- (SHIME 2) for five weeks of SHIME experiments. The values are compared to those of the second week of control: those in red are higher, white is within the same range, and green is lower. SHIME1
i CTRWl CTRW2 TREÂT1 TREAT2 TREAT3 ..........The*""*"! ......: _AC CoHorms _____ 2.17E + 07 ___1.11E + 08 1.14E4Q72.42E4O8 8.11E + 07 3.35E + 077J7E + 07 1,166 * 072.90E + 07 Clostridia) _TC CoHorms ~ 5.49E + 063.17E + O7 127E + 07120E + 08 1.80E + 07230E + 07 1.02Ε * 07£ 5-59 * 06 Clostridia} _, 1.55E4O7 1.60E + 07 3.84EKJ7 7.42E + 06 8.54E + 06 ..................-.......... — .................. t uCCdforms 2.07E + O7 4.B7E + O7 2.91E407 1.30E + Ó7 1.77E-O7
SHIME 2
CTRWl
CTRW2
TREAT1: TREAT2
Ctostricha
Coàíõims 9.82E + O7 . 8.S5E + 07 Clostridia ......... I τζ * 1 ....... 813E + 0G | 37OE + OS CoHorms ; IL 4.03E * O7 ! 7.81E + 07 Ctoslridiâ 1.57E + 07 I 4.43E + 07 CoHorms ......... [DC i ..... 5.75E + O7 ) 1.41E * 08
6.72E + 07
552E + O7 sjíie & w
E.98E + C7
4.ME + 0
1.79E + 08
3.53E + 07
4.0S & + Ú7
TREAT3
3.91E + Ô7 1.156 * 07 1. SOE * 07 1.53E + O7 1.ME * 07
In total, Mixture ¹ induces an increase in Clostridia and Coliforms in the proximal colon during the first week of treatment (with the exception of Coliforms in AC), but at the end of the treatment period the values are comparable or lower than those in the period of control. The descending colon was not affected (this is in line with the fact that Mixture ¹ fermented mainly in the first part of the colon). Mixture ¹ * induces a general decrease in Clostridia and Coliforms at the end of treatment with the exception of Clostridia in the ascending colon.
Conclusions
Both mixtures fermented well, which resulted in less toxic ammonium production. Partial replacement of FOS and inulin
69/72 by AG (Mixture ¹ *) changes the intestinal fermentation from an intensified fermentation in the proximal colon to a gradual fermentation in the complete colon, as shown by acidification of all parts of the colon and more gradual production of gas. The substitution of FOS and inulin for AG induces differences in SCFA production. The butyrogenic effect of Mixture ¹ was higher. Mixture ¹ * induced higher concentrations of propionate. Both mixtures exhibited bifidogenic properties. The partial replacement of FOS and inulin by acacia gum has no negative consequences for its prebiotic activity. In addition, Mixture ¹ * induces a greater increase in Lactobacilli in the ascending colon compared to Mixture ¹ . AG is more selective and specific in fermentation compared to FOS and inulin.
According to scientific literature, inulin-type prebiotics, which include FOS and inulin, resist enzymatic digestion in the upper gastrointestinal tract with the result that they reach the colon virtually intact and undergo bacterial fermentation. These products are mainly bifidogenic but, according to some reports, the growth of Lactobacilli can also be stimulated. The effects they have on other organisms in the gut are less consistent. From a physiological point of view, these dietary fibers are fermented to a great extent by a wide variety of anaerobic bacteria (mainly Bifidobacteria and bacteroidetes) in the proximal colon, which results in an increase in bacterial biomass, an increase in fecal mass, an change in intracolonic pH, and in the production of SCFAs (mainly acetate, butyrate and propionate). AG, on the other hand, also reaches the colon intact and has been correlated mainly with the increased number of Bifidobacteria and Lactobacilli and a greater production of propionate.
Microbial community activity
Some conclusions of the present study regarding the activity of the microbial community are summarized below.
Both products fermented well and provided clear indications of prebiotic activity.
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The administration of both mixtures induces acidification of the simulated colon reactors, which is indicative of increased SCFA production and a healthier intestinal environment.
The partial replacement of FOS and inulin by acacia gum changes the intestinal fermentation profile from an intensified fermentation in the proximal colon to a more gradual fermentation in the complete colon, as shown (i) by the acidification of all the colon compartments in the case the administration of Mixture ¹ *, which was also confirmed in the batch experiment, (ii) a smaller and more gradual production of gas in the case of the administration of Mixture ¹ * (batch experiment), and (iii) higher concentrations of lactate in the ascending colon with the administration of Mixture ¹ .
The partial replacement of FOS and inulin by acacia gum induces differences in the production of bacterial SFCA. The butyrogenic effect of Mixture ¹ was higher than that of Mixture ¹ *, although Mixture ¹ * exhibited a higher concentration of propionate (although not always supported by statistics). This shows that although both mixtures have a very positive effect in terms of SCFA production (butyrate and propionate are considered to be beneficial for health), the specific fermentation profile depended on the specific composition of the mixtures.
The good fermentation of the two products, as well as the higher saccharolytic metabolism, are also confirmed by a decreased production of ammonium during the treatment period without statistical differences between the products.
Composition of the microbial community
Some conclusions of the present study regarding the composition of the microbial community are summarized below. QPCR was used as a culture-independent technique to monitor the total of bacteria, Bifidobacteria, Lactobacilli, Firmicutes and Bacteroidetes.
Both mixtures exhibited bifidogenic properties. The increase in Bifidobacteria induced by Mixture ¹ is statistically greater than that of Mixture ¹ *, however the partial replacement by acacia gum
71/72 also increased Bifidobacteria, confirming that this substitution has no negative consequences for its prebiotic activity. In addition, Mixture ¹ * induces a greater increase in Lactobacilli in the ascending colon compared to Mixture ¹ .
A decrease in total bacteria could be seen for Mixture ¹ * in the ascending colon during the first week of treatment. This decrease is mainly correlated with the decrease in the dominant family of Firmicutes and Bacteroidetes in the same colon compartment. This can be explained by the fact that acacia gum is more selective and specific for fermentation compared to FOS and inulin, and that bacteria need a longer time to adapt to Mixture ¹ *.
In addition, a prolonged treatment with both mixtures induces a decrease in Clostridia and Coliforms at the end of the treatment (Mixture ¹ *> Mixture ¹ ).
Mucosa-associated microbial community
Mixture ¹ is mainly fermented in the proximal colon and has an immediate effect on AR-PI in the ascending colon. During the second and third weeks, the bacteria begin to adapt to the product. The bacteria in the transverse colon were also affected, but it takes the entire treatment period to observe this effect. No effect was seen on the descending colon. Therefore, Mixture ¹ * is probably a more balanced formulation and less easier to ferment. For this reason, it has an effect on the entire colon.
In general, it can be seen that both mixtures exhibit prebiotic activity. The partial substitution of FOS and inulin by AG did not diminish the potential of Mixture ¹ *, as shown by the increased production of SCFA propionate and butyrate, intestinal acidification and stimulation of Lactobacilli and Bifidobacteria. On the other hand, Mixture ¹ * acidified more gradually and throughout the entire simulated colon.
It should be understood that several changes and modifications to the currently preferred modalities described here will be apparent to
72/72 elements skilled in the art. Such changes and modifications can be made without deviating from the character and scope of the present object and without diminishing its intended advantages. It is intended, therefore, that such changes and modifications are covered by the attached claims.
The invention is claimed as follows.
1/4

权利要求:
Claims (18)
[1]
1. Nutritional composition for administration to an individual, characterized by the fact that it comprises:
a soluble fiber comprising a fructo-oligosaccharide (FOS), in an amount of 35 to 44% by weight;
a polysaccharide, the polysaccharide being acacia gum (AG) and present in an amount of 38% to 50% by weight; and inulin, in an amount of 12 to 24% by weight;
with FOS and polysaccharide being present in a weight ratio of 62:38 to 38:62; and FOS and inulin are present in a weight ratio of 82:18 to 58:42, and which further comprises at least one insoluble fiber in an amount effective to improve digestive function in the individual, with at least one fiber insoluble is an outer fiber of the pea, and the soluble fiber and insoluble fiber are present in a ratio between 1.5: 1 and 1: 1.5.
[2]
2. Nutritional composition according to claim 1, characterized by the fact that FOS and polysaccharide are present in a weight ratio of 55:45 to 45:55, or that FOS and inulin are present in a proportion in weight from 76:24 to 64:36.
[3]
3. Nutritional composition, according to claim 1, characterized by the fact that:
FOS is present in an amount between 1.5-5.5 g / L, AG is present in an amount of 2.5-5.5 g / L, and inulin is present in an amount of 0.5 -2.5 g / L.
[4]
4. Nutritional composition according to claim 3, characterized by the fact that it also comprises up to 10 g / L of partially hydrolyzed guar gum.
[5]
5. Nutritional composition, according to claim 4, characterized by the fact that:
FOS and AG is present in a total amount between 2.5-3.5
2/4 g / L, inulin is present in an amount between 1.25-1.75 g / L, and the outer fiber of the pea is present in an amount between 3.25-4.25 g / L.
[6]
6. Nutritional composition, according to claim 5, characterized by the fact that soluble fiber and insoluble fiber are present in a ratio of 1.25: 1 to 1: 1.25, respectively.
[7]
7. Nutritional composition according to claim 1 characterized by the fact that it also comprises at least one of the following: antioxidants, fish oils, DHA, EPA, vitamins, minerals, phytonutrients, proteins, fats, probiotics, and their combinations.
[8]
8. Nutritional composition according to any one of claims 1 to 7, characterized by the fact that it is for use in promoting the balance of intestinal microbiotics and health.
[9]
9. Nutritional composition, according to claim 8, characterized by the fact that the said balance of intestinal microbiotics and health improves the patient's tolerance to various medical treatments that lead to disorders of the gastrointestinal tract, such as radiotherapy, chemotherapy, gastrointestinal surgery, anesthesia, administration of antibiotics, analgesic drugs or treatments for diarrhea.
[10]
10. Nutritional composition, according to claim 8, characterized by the fact that the said balance of intestinal microbiotics and health promotes systemic benefits, such as better recovery growth, for children.
[11]
11. Nutritional composition, according to claim 8, characterized by the fact that the said balance of intestinal microbiotics and health promotes the reduction of the hospitalization time for patients, allowing such patients to obtain acceptable nutritional levels and feeding goals with greater tolerance to such formulations, thus increasing compliance with feeding requirements, and reducing complications.
3/4
[12]
12. Nutritional composition, according to claim 11, characterized by the fact that the referred reduced complications are selected from the group consisting of diarrhea, constipation, gastroesophageal reflux, regurgitation, vomiting, and their combinations.
[13]
13. Nutritional composition according to claim 8, characterized by the fact that the said balance of microbiotas in the intestine and health stimulates an individual's immune system.
[14]
14. Nutritional composition, according to claim 8, characterized by the fact that the said balance of intestinal microbiotics and health is:
(i) increased butyrate production in a patient's colon, comprising administering an effective amount of the nutritional composition, as defined in any of claims 1 to 8, to the patient to increase butyrate production compared to formulations that do not contain AG to produce cell proliferation in the colon and lower the pH of the colon to inhibit the growth of pathogenic bacteria, or (ii) a continuous overtime exchange in microbiota balance favoring beneficial bacteria, such as bifidobacteria, lactobacilli or bifidobacteria and lactobacilli, or ( iii) sustained fermentation, production of small chain fatty acid, change in saccharolytic fermentation from the ascending colon to the descending colon, leading to the sustained fermentation of carbohydrate in the descending colon and the reduction of protein fermentation or combinations thereof throughout the colon,
[15]
15. Nutritional composition, according to claim 14, characterized by the fact that said butyrate production leads to at least one of the following: anti-inflammatory benefits that help to protect the patient's intestinal barrier; better absorption of minerals, normalization of gastrointestinal transit time, decreased diarrhea.
[16]
16. Nutritional composition according to claim 14, characterized by the fact that a sustained change over time in the balance of microbiota reduces pathogens, in particular Clostridia.
4/4
[17]
17. Nutritional composition according to claim 16, characterized by the fact that clostridia is reduced in the distal colon.
[18]
18. Nutritional composition according to claim 14, characterized by the fact that by sustained fermentation, small production of a fatty acid chain, a change in saccharolytic fermentation from the ascending colon to the descending colon:
(i) there is better nutrient reabsorption, water reabsorption or electrolyte reabsorption, or combinations thereof, or (ii) improved intestinal regularity, improved constipation, improved diarrhea, improved irritable bowel syndrome, improved Crohn's disease, colitis improved ulcerative, or combinations thereof, or (iii) there is a reduced pH, a preferred substrate for colonocytes, better presentation of nutrients for colonocytes, throughout the length of the colon.
1/28
Probability of reaching DEI
Days

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引用文献:

---

公开号 | 申请日 | 公开日 | 申请人 | 专利标题

---

---

US5952314A|1994-04-01|1999-09-14|Demichele; Stephen Joseph|Nutritional product for a person having ulcerative colitis|

---

ES2123903T5|1995-08-04|2011-02-22|N.V. Nutricia|NUTRITIVE COMPOSITION CONTAINING FIBER.|

---

AT308254T|1998-12-15|2005-11-15|Nestle Sa|BALANCE MIXTURE FOR ENTERAL COMPOSITION|

---

HU0204546A3|2000-03-01|2003-10-28|Nestle Sa|Carbohydrate formulation for enhancement of immune response|

---

EP1175905A1|2000-07-24|2002-01-30|Societe Des Produits Nestle S.A.|Nutritional Composition|

---

US6592863B2|2000-08-22|2003-07-15|Nestec S.A.|Nutritional composition|

---

EP1243273A1|2001-03-22|2002-09-25|Societe Des Produits Nestle S.A.|Composition comprising a prebiotic for decreasing infammatory process and abnormal activation of non-specific immune parameters|

---

GB0308104D0|2003-04-08|2003-05-14|Novartis Nutrition Ag|Organic compounds|

---

ITMI20040956A1|2004-05-12|2004-08-12|Curti Alessandro|FOOD COMPOSITIONS|

---

EP1597978A1|2004-05-17|2005-11-23|Nutricia N.V.|Synergism of GOS and polyfructose|

---

US8252769B2|2004-06-22|2012-08-28|N. V. Nutricia|Intestinal barrier integrity|

---

EP1940248B1|2005-10-05|2009-12-16|Nestec S.A.|Use of a nutritional formulation for promoting catch-up growth|

---

ITMI20062031A1|2006-10-23|2008-04-24|Velleja Res Srl|COMPOSITIONS FOR THE PREVENTION OF DEPAUPERAMENTO OF THE INTESTINAL FLORA AND OF THE DAMAGE OF ORGAN SUBSEQUENT TO ANTIBIOTIC THERAPY|

---

CA2668613C|2006-11-07|2016-12-13|The Procter & Gamble Company|Fiber containing compositions and methods of making and using same|

---

ITMI20071214A1|2007-06-15|2008-12-16|S I I T Srl Servizio Internazi|COMPOSITIONS BASED ON PREBIOTIC AND IMMUNOGENIC COMPONENTS FOR THE PREVENTION AND TREATMENT OF GASTROENTERIC DISORDERS FROM DISBIOSIS AND / OR ALTERATIONS OF THE NORMAL INTESTINAL FLORA|

---

ES2392002T3|2007-07-18|2012-12-03|Campina Nederland Holding B.V.|Thermostable nutritional drink and method for preparing this|

---

WO2009075564A1|2007-12-10|2009-06-18|N.V. Nutricia|Paediatric fibre mixture|

---

JP5992654B2|2007-12-21|2016-09-14|ニュートリー株式会社|Composition for intestinal regulation and / or improvement of bowel movement|

---

AU2010319490B2|2009-11-12|2015-03-19|Société des Produits Nestlé S.A.|Nutritional composition for promoting gut microbiota balance and health|AU2010319490B2|2009-11-12|2015-03-19|Société des Produits Nestlé S.A.|Nutritional composition for promoting gut microbiota balance and health|

---

CA2839524C|2011-06-20|2016-05-17|H.J. Heinz Company|Probiotic compositions and methods|

---

WO2012175639A1|2011-06-22|2012-12-27|Universite De Rouen|Arabinogalactan proteins for use as an antiparasitic agent|

---

FI126711B|2011-10-12|2017-04-13|Gut Guide Oy|Assessing the health risk associated with a serotonin deficiency|

---

RU2014119930A|2011-10-18|2015-11-27|Нестек С.А.|COMPOSITION INTENDED FOR USE IN STIMULATION OF HEALTHY BONE GROWTH AND / OR IN PREVENTION AND / OR THERAPY OF BONE DISEASES|

---

TW201318566A|2011-11-01|2013-05-16|Jimmy Lu|Composition and method of delivery of l-arabinose and select compounds|

---

IN2014DN07752A|2012-02-29|2015-05-15|Ethicon Endo Surgery Inc|

---

ITRM20120084A1|2012-03-07|2013-09-08|Aboca Spa Societa Agricola|PREBIOTIC MIXTURE.|

---

WO2014007606A1|2012-07-05|2014-01-09|N.V. Nutricia|Product for use in the prophylactic or therapeutic treatment of a negative emotion or introvert behaviour|

---

JP2015535280A|2012-11-01|2015-12-10|レイクスユニフェルシテイト フローニンゲン|Methods and compositions for stimulating beneficial bacteria in the gastrointestinal tract|

---

US8906668B2|2012-11-23|2014-12-09|Seres Health, Inc.|Synergistic bacterial compositions and methods of production and use thereof|

---

US20150296851A1|2012-11-27|2015-10-22|Shanghai Jiao Tong University|Compositions for Balancing Gut Microbiota and the Preparation and the Uses thereof|

---

US10973861B2|2013-02-04|2021-04-13|Seres Therapeutics, Inc.|Compositions and methods|

---

CN110917220A|2013-02-04|2020-03-27|赛里斯治疗公司|Therapeutic compositions and methods of use thereof|

---

EP2983662A4|2013-03-15|2016-09-21|MicroBiome Therapeutics LLC|Activated soy pod fiber|

---

JP2016519664A|2013-03-15|2016-07-07|セレス セラピューティクス インコーポレイテッド|Microbial composition and method based on network|

---

GB201305708D0|2013-03-28|2013-05-15|Clasado Inc|Novel use|

---

WO2014165975A1|2013-04-11|2014-10-16|Bright Drinks Inc.|Compositions for prevention and/or treatment of gastrointestinal imbalances in digestive disorders|

---

ITMI20131467A1|2013-09-06|2015-03-07|Sofar Spa|USE OF A COMPOSITION INCLUDING MICRO-ORGANISMS TO INCREASE THE INTESTINAL PRODUCTION OF BUTIRRIC ACID, FOLIC ACID OR NIACINE ACID AND / OR TO REDUCE THE INTESTINAL PRODUCTION OF SUCCINIC ACID|

---

WO2015077794A1|2013-11-25|2015-05-28|Seres Health, Inc.|Synergistic bacterial compositions and methods of production and use thereof|

---

US9956282B2|2013-12-16|2018-05-01|Seres Therapeutics, Inc.|Bacterial compositions and methods of use thereof for treatment of immune system disorders|

---

CN105828641A|2013-12-20|2016-08-03|雀巢产品技术援助有限公司|Nutritional compositions for reducing intestinal pathogens|

---

CN104187624B|2014-08-07|2016-06-08|逯明福|Comprehensive nutrition powder and its preparation method|

---

WO2016029113A1|2014-08-22|2016-02-25|Abbott Laboratories|Methods of increasing endogenous production of beta-hydroxy-beta-methylbutyrate|

---

US9539344B2|2014-09-30|2017-01-10|Kimberly-Clark Worldwide, Inc.|Creped prebiotic tissue|

---

US10441603B2|2014-09-30|2019-10-15|Kimberly-Clark Worldwide, Inc.|Synergistic prebiotic composition|

---

JP6868562B2|2014-10-31|2021-05-19|ペンデュラム セラピューティクス， インコーポレイテッド|Methods and compositions for microbial treatment and diagnosis of disorders|

---

CN104432069A|2014-12-22|2015-03-25|威海百合生物技术股份有限公司|Gastrointestinal smoothening tablets|

---

JP6338113B2|2015-03-31|2018-06-06|株式会社東洋新薬|Lean body weight increase agent|

---

CN108369223B|2015-12-30|2021-07-06|雀巢产品有限公司|Method for determining lean body mass|

---

MX2018007398A|2015-12-31|2018-08-15|Nestec Sa|Composition for improving mouthfeel.|

---

US20180030403A1|2016-07-28|2018-02-01|Bobban Subhadra|Devices, systems and methods for the production of humanized gut commensal microbiota|

---

CA3038061A1|2016-09-22|2018-03-29|The University Of Chicago|Immune response modulation using live biotherapeutics, for conditions such as allergy desensitization|

---

US20200085884A1|2016-12-15|2020-03-19|The Board Of Trustees Of The Leland Stanford Junior University|Compositions and methods for modulating growth of a genetically modified gut bacterial cell|

---

CN108245530A|2016-12-28|2018-07-06|兰州奇正生态健康品有限公司|A kind of composition with functions of loosening bowel relieving constipation and preparation method thereof and purposes|

---

ES2683014B1|2017-03-23|2019-01-16|Cuetara S L|Child cookie without added sugars|

---

EP3641566A1|2017-06-21|2020-04-29|Abbott Laboratories|Methods for increasing growth of beneficial bacteria in the gastrointestinal tract|

---

IT201700108033A1|2017-09-27|2019-03-27|Neilos S R L|Composition for the treatment of constipation|

---

IT201700108039A1|2017-09-27|2019-03-27|Neilos S R L|Composition for the treatment of constipation|

---

EP3466276A1|2017-10-05|2019-04-10|Pharmactive Biotech Products, S.L.|Dietary fiber composition for protecting bioactive compounds during the physiological digestion process|

---

AU2017438436B2|2017-10-31|2022-01-13|Morinaga Milk Industry Co., Ltd.|Muscle-building composition|

---

EP3897211A1|2018-12-19|2021-10-27|Cosucra Groupe Warcoing S.A.|Composition comprising chicory root and pea cell wall fiber for treating brachyspira infections|

---

JP2022517237A|2019-01-18|2022-03-07|シー・ピー・ケルコ・ユー・エス・インコーポレイテツド|Prebiotic compositions and their use|

---

WO2020161522A1|2019-02-06|2020-08-13|Thd S.P.A.|Fiber-based composition|

---

FR3093427B1|2019-03-05|2021-03-05|Mativa Tech|COMPOSITION FOR USE IN THE PREVENTION AND / OR TREATMENT OF DYSBIOSIS|

---

CN109820865A|2019-04-09|2019-05-31|福州大学|The application of xylo-oligosaccharide and the guar gum complex composition of partial hydrolysis in pre- preventing obesity and health care product|

---

CN114072013A|2019-05-29|2022-02-18|N·V·努特里奇亚|Non-digestible oligosaccharides for reducing colonic protein fermentation|

---

CN110251530A|2019-07-09|2019-09-20|大连大学|A kind of preparation method and its clinical application of larch arabinogalactan composition|

法律状态:
2017-06-27| B07A| Technical examination (opinion): publication of technical examination (opinion)|

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2017-11-14| B15K| Others concerning applications: alteration of classification|Ipc: A23L 29/244 (2016.01), A23L 29/25 (2016.01), A23L |

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2017-11-14| B06F| Objections, documents and/or translations needed after an examination request according art. 34 industrial property law|

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2018-03-06| B09A| Decision: intention to grant|

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2018-03-20| B16A| Patent or certificate of addition of invention granted|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 11/11/2010, OBSERVADAS AS CONDICOES LEGAIS. |

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2019-10-15| B25A| Requested transfer of rights approved|

优先权:

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申请号 | 申请日 | 专利标题

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US26049509P| true| 2009-11-12|2009-11-12|

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US61/260,495|2009-11-12|

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US26443009P| true| 2009-11-25|2009-11-25|

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US61/264,430|2009-11-25|

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US39480510P| true| 2010-10-20|2010-10-20|

---

US1/394,805|2010-10-20|

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PCT/US2010/056321|WO2011060123A1|2009-11-12|2010-11-11|Nutritional composition for promoting gut microbiota balance and health|

---