Dietary fiber composition

Abstract

The present invention relates to a dietary fiber mixture having a composition tailored to be fermentable by diverse microbiota profiles of diverse individuals, thereby providing health benefits related to the production of short-chain fatty acids. It also relates to nutritional compositions, such as foods or beverages, containing such dietary fiber mixture compositions. In a first aspect, the present invention relates to a dietary fiber composition comprising a mixture of the following dietary fibers: a. isolated fructooligosaccharides (FOS), b. isolated inulin, c. isolated resistant maltodextrin, d. isolated resistant dextrin, e. isolated galactomannan polysaccharide, and f. isolated partially hydrolyzed galactomannan. In a second aspect, the present invention relates to a nutritional composition comprising the dietary fiber composition of the present invention.

Description

[Technical Field]

[0001] The present invention relates to a dietary fiber mixture having a composition tailored to be fermentable by diverse microbiota profiles of diverse individuals, thereby providing health benefits associated with the production of short-chain fatty acids, and to nutritional compositions, such as foods or beverages, containing such a dietary fiber mixture composition. Background technology [Background technology]

[0002] Dietary fiber is a natural and essential component of many phytonutrients, such as fruits, vegetables, grains, and cereals, and is also found in milk. Dietary fiber is usually added to a wide variety of foods. Dietary fiber is fermented by the microflora of the individual who consumes it. During fermentation by the microflora, metabolic products, particularly short-chain fatty acids such as acetate, propionate, and butyrate, are produced, which provide numerous health benefits to consumers.

[0003] The benefits associated with dietary fiber consumption are described, for example, by Liu et al. in "A Double-Edged Sword for Health?, Adv Nutr 2018;9:21-29," and include: a) Improved intestinal function, b) improved postprandial glycemic response; c) Lowering blood cholesterol, d) improvement of intestinal homeostasis, e) Improved energy metabolism, f) Prevention of obesity and overweight; g) effects on insulin sensitivity; h) Prevention and treatment of type 2 diabetes; i) anti-inflammatory effect; j) Strengthening of intestinal barrier function, k) Strengthening mucosal immunity, l) Effects on the brain-gut axis.

[0004] Dietary fiber is commonly added to various nutritional compositions to provide various health benefits. Many prior art documents provide a long list of possible fibers, from which one or more fibers must be selected. For example, European Patent Application No. 3513665 discloses a nutritional supplement containing prebiotics, among other types of ingredients. The prebiotic is preferably a soluble dietary fiber, and may be selected from the group consisting of maltodextrin, inulin, oligofructose, lactose, lactulose, resistant starch, fructooligosaccharides (FOS), galactooligosaccharides (GOS), transgalactooligosaccharides (TOS), wheat bran-derived arabinoxylooligosaccharides (AXOS), xylooligosaccharides (XOS), isomaltooligosaccharides (IMO), gentiooligosaccharides (GTO), glucooligosaccharides, pectin oligosaccharides, soybean oligosaccharides, lactosucrose, polydextrose, sugar alcohols, alpha-glucans, beta-glucans, wheat dextrin, guar gum, flaxseed gum, fenugreek gum, acacia gum, psyllium, and raffinose. Preferably, the prebiotic is maltodextrin. The supplement is disclosed as providing benefits related to weight loss and / or weight maintenance. All examples include maltodextrin as a prebiotic. The document does not provide any suggestion of any particular fiber combinations that are particularly beneficial, other than specific reference to maltodextrin.

[0005] U.S. Patent Application Publication No. 2011 / 02741 discloses compositions containing dietary fiber, more specifically, compositions containing a combination of gelling and non-gelling fibers. Such compositions are disclosed as promoting gastrointestinal and / or cardiovascular health. Non-limiting examples of gelling dietary fibers include psyllium, unmodified pectin, mannans (such as guar gum, locust bean gum, konjac, xanthan gum, glucomannan, and galactomannan), beta-glucans, arabinans, galactans, aligns, agar, propyl cellulose and methyl cellulose (such as hydroxypropyl methyl cellulose and carboxymethyl cellulose), gelling carrageenans, and combinations thereof. Non-limiting examples of non-gelling dietary fibers include inulin, gum arabic (acacia gum), cocoa arabinogalactan, resistant dextrin, high-methyl pectin, cellulose, raffinose, stachyose, oligosaccharides (such as fructooligosaccharides, soybean oligosaccharides, galactooligosaccharides, gentiooligosaccharides, xylooligosaccharides, isomaltooligosaccharides, and arabinoxylanoligosaccharides), lactulose, hydrolyzed guar gum, lignin, bran and cereal fibers (such as oat hull fiber), oat bran, wheat bran, rice bran, non-gelling carrageenan, invert modified starch, resistant starch, slow-digestible starch, resistant maltodextrin, sugar beet fiber, oilseed fiber such as that derived from flax, and combinations thereof. A specific example is provided below: a mixture of inulin, psyllium, and oat hull fiber.

[0006] Another example is European Patent Application No. 1692949, which discloses a water-soluble dietary fiber-containing composition that can be incorporated into various foods and can provide physiological effects, such as suppressing blood sugar levels and regulating intestinal function, to consumers who consume the fiber-containing composition. The fibers disclosed include the water-insoluble fiber cellulose, wheat bran, apple-derived fiber, sweet potato- and chitin-derived fiber, water-soluble fiber pectin, konjac powder (mannan), alginate, propylene glycol alginate, guar gum, agar, indigestible dextrin, polydextrose, branched maltodextrin, inulin, and guar gum hydrolysate. Oligosaccharides such as fructooligosaccharides, galactooligosaccharides, and xylooligosaccharides are also mentioned. In the examples, only the following combinations are disclosed: a. Indigestible dextrin and alginate (sodium alginate, etc.), b. Propylene glycol ester of indigestible dextrin and alginic acid, c. Indigestible dextrin and agar, d. Polydextrose and alginate, e. branched maltodextrin and alginate, f. Resistant dextrin, sodium alginate or agar and resistant starch.

[0007] It is further known from the prior art that different bacterial strains have different fermentation abilities, and that not all fibers can be fermented by all types of bacteria present in an individual's microbiota. It is also known that the microbiota can vary from individual to individual. Nevertheless, the prior art literature does not address the problem of providing a dietary fiber mixture containing fibers that can be optimally fermented by most or all of the many different microbiota environments found in different individuals. The present invention aims to solve this problem. Summary of the Invention

[0008] In a first aspect, the present invention provides a dietary fiber comprising: a. isolated fructooligosaccharides (FOS), b. isolated inulin, c. isolated resistant maltodextrin; d. isolated resistant dextrin; e. isolated galactomannan polysaccharides, and f. Isolated partially hydrolyzed galactomannan The present invention relates to a dietary fiber composition comprising a mixture of:

[0009] In a second aspect, the present invention relates to a nutritional composition comprising the dietary fiber composition of the present invention.

[0010] In a third aspect, the present invention relates to a method for producing a nutritional composition according to the present invention, the method comprising the step of mixing a dietary fibre composition of the present invention with other components of the nutritional composition.

[0011] In a fourth aspect, the present invention relates to a dietary fiber composition according to the invention or a nutritional composition according to the invention for use in therapy. [Brief explanation of the drawings]

[0012] [Figure 1] Butyrate production rates (mmol / hr) calculated for each fermentable substrate from ex vivo fermentation experiments on fecal samples from volunteers. Error bars represent standard deviations to illustrate inter-individual variability. The number of measurements varies by fiber and can be found in the Materials and Methods section of Example 1.

[0013] [Figure 2] Propionate production rates (mmol / hr) calculated for each fermentable substrate from ex vivo fermentation experiments on fecal samples from volunteers. Error bars represent standard deviation to illustrate inter-individual variability. The number of measurements varied by fiber and can be found in the Materials and Methods section of Example 1.

[0014] [Figure 3]Expected average fermentation profile for each mixture based on volunteers in our database. Butyrate production rates are shown in black and propionate production rates are shown in gray.

[0015] [Figure 4] Results from HbA1c, insulin sensitivity (ISI-OGTT), and fasting insulin measurements. Changes from baseline to week 16 for intervention (dark gray) versus placebo (light gray) in (B) HbA1c, (C) insulin sensitivity (assessed using ISI-OGTT), and (D) fasting blood insulin (μU / mL) within the subgroup including participants with baseline HbA1c levels <6.0%.

[0016] [Figure 5] Difference in gut microbiota diversity and richness scores between participants who consumed the fiber blend of the present invention (series labeled "Yes") and participants who did not consume the fiber blend (series labeled "No"). * denotes pCorr<0.05.

[0017] [Figure 6] Results from stress and bowel symptom scores for completed participants (N=37). (A) Change from baseline to week 12 in perceived stress score (PSS); (C) Total Gastrointestinal Symptom Rating Scale (GSRS) scores for the intervention group (light gray) and the control group (dark gray). * denotes pCorr<0.05. DETAILED DESCRIPTION OF THE INVENTION

[0018] The dietary fiber compositions of the present invention contain a combination of fibers that are best fermented across individuals with different microbiota, thus maximizing the rate of butyrate and propionate production.

[0019] Dietary fiber composition Since microbiota vary from individual to individual, the best fermented fiber also varies from individual to individual. The inventors evaluated the short-chain fatty acid production rate during the fermentation of a wide range of fibers by many different microbiota, and identified the fiber that was best fermented across the entire subject population to provide sufficient short-chain fatty acid metabolites. Based on this, they developed a dietary fiber composition that ensures that sufficient short-chain fatty acids can be produced in a timely manner when any subject ingests the composition and ferments the dietary fiber composition by the subject's microbiota. Therefore, the dietary fiber blend composition is advantageous in that it contains all the fibers required to enable sufficient production of short-chain fatty acids, especially butyrate and propionate, in a wide variety of individuals. Compared to other blends, it is optimized to be compatible with most microbiota of a consumer population as a one-size-fits-all composition.

[0020] The essential components of the dietary fiber composition are fructooligosaccharides, inulin, resistant maltodextrin, resistant dextrin, galactomannan polysaccharides, and partially hydrolyzed galactomannans. Optionally, the dietary fiber composition also contains galacto-oligosaccharides. The dietary fiber composition is based on these fibers in isolated form, i.e., they are not provided in the form of a complex plant source containing such fibers. However, the term "isolated" does not exclude the presence of minor or trace amounts of other compounds, such as impurities not removed by the purification process or by-products obtained during fiber synthesis. The term "isolated" does not exclude the presence of multiple fibers from the above-listed fibers combined as a single component, provided that such a fiber source contains substantially only the above-listed fibers. This may be the case, for example, with an isolated fructan component that is a mixture of inulin and fructooligosaccharides.

[0021] In order to control the amount of fiber required to be present in the composition, it is advantageous for fiber to be in an isolated form.When fiber is provided in the form of a complex matrix, such as natural sources, such as grain, it is often difficult to determine whether desired fiber is present and how much it is present in such a matrix.Since the present fiber composition is adjusted to be compatible with the most diverse microbiota types, it is important that no fiber is missing from the mixture, and preferably, each fiber is present in the preferred amount described herein.For this purpose, isolated fiber is used in the present dietary fiber composition.

[0022] Furthermore, the fiber composition may preferably also contain a source of arabinoxylan and / or β-glucan, which may be either an isolated form of the arabinoxylan and / or β-glucan source, or a more complex component that includes a source of arabinoxylan and / or β-glucan, such as, for example, oat and / or wheat fiber.

[0023] Fructooligosaccharides (FOS) and inulin are both fructans. Inulin is a polymer of D-fructose residues linked by β(2→1) linkages to a terminal α(1→2)-linked D-glucose. Inulin has the general structure Glu-Fru n (or GF n ), where n is 10-60 (degree of polymerization of 10-60). FOS has the general structure Glu-Fru n (or GF n ), where n is 2-7 (degree of polymerization of 2-7). The fructose units may be linked by a variety of linkages, including β(2→1) and β(1→2). Both inulin and FOS are non-digestible and therefore not broken down by enzymes in the digestive tract of an individual who ingests them. Therefore, inulin and FOS are available for fermentation by the microflora of such an individual.

[0024] It is particularly advantageous for the composition to include both FOS and inulin, as combining fructans of different lengths increases SCFA production across different individuals compared to single-length fructans, and this applies to both butyrate and propionate production.

[0025] We identified that a mixture of FOS and inulin produced the most butyrate and propionate of the fibers tested (Figure 1).

[0026] Resistant maltodextrin is a soluble, non-viscous, digestion-resistant dietary fiber. It is an oligosaccharide formed by 3 to 20, preferably 3 to 17, glucose units linked by α(1→4) bonds, formed by a process of "retrogradation" in which the glucose chains (amylose and amylopectin) rearrange after heating and cooling, and has the chemical formula C( 6n )H( 10n+2 )O( 5n+1 Resistant maltodextrin has an advantage for producing butyrate because its fermentation has less interindividual variability compared to most other dietary fibers. The average propionate production upon fermentation by a diverse microbiota is also higher than most other dietary fibers tested (see Figure 2).

[0027] Resistant dextrin has the chemical formula (CH 10 Resistant dextrin is a digestion-resistant dietary fiber formed from glucose units primarily linked by α(1→4) or α(1→6) linkages with a β(1→6) or α(1→2) bond, branched through other linkages such as β(1→6), β(1→2), α(1→6), and α(1→2). Its branched structure is responsible for its resistance to digestive enzymes. Resistant dextrin is typically obtained by partial enzymatic hydrolysis of starch, followed by thermal degradation under acidic conditions. The latter step is responsible for the branching of the structure, conferring resistance to digestion to dextrin.

[0028] Advantageously, the average butyrate production rate during fermentation of resistant maltodextrin and resistant dextrin by diverse microbiota is higher than that of other fibers, such as chitosan, microchitosan, psyllium, cellulose, and NOPA. Furthermore, interindividual variability is lower than that of many other fibers, as evidenced by the short error bars associated with the resistant maltodextrin and resistant dextrin histograms in Figures 1 and 2. Thus, these fibers were metabolized to butyrate by the microbiota from all donors used in Example 1, making these fibers particularly advantageous for use in foods intended for use in a wide variety of subjects.

[0029] Galactomannan polysaccharides have a mannose backbone consisting of mannose units linked by α(1→4) linkages and branched with 1-6 linked galactose side groups. Various galactomannan polysaccharides differ in their higher mannose-to-galactose ratios. Examples of galactomannan polysaccharides include fenugreek gum (having a mannose:galactose ratio of approximately 1:1), guar gum (having a mannose:galactose ratio of approximately 2:1), tara gum (having a mannose:galactose ratio of approximately 3:1), locust bean gum (having a mannose:galactose ratio of approximately 4:1), and cassia gum (having a mannose:galactose ratio of approximately 5:1). Preferably, the galactomannan has a mannose:galactose ratio of 1:1 to 3:1, more preferably 1.5:1 to 2.5:1. Most preferably, the galactomannan is guar gum.

[0030] The partially hydrolyzed galactomannan is a dietary fiber obtained by controlled enzymatic hydrolysis of the above-mentioned galactomannan polysaccharide. Preferably, the hydrolyzed galactomannan has a mannose:galactose ratio of 1:1 to 3:1, more preferably 1.5:1 to 2.5:1. Most preferably, it is partially hydrolyzed guar gum.

[0031] Galactomannan polysaccharides and partially hydrolyzed galactomannans are particularly advantageous with respect to their ability to be metabolized to propionate by the microbiota from the donors in Example 1. Indeed, among the fibers tested in Example 1, galactomannan polysaccharides and partially hydrolyzed galactomannans (partially hydrolyzed guar gum) had the highest mean propionate production rates. Furthermore, although both galactomannan polysaccharides and partially hydrolyzed galactomannans exhibited high inter-individual variability in propionate production rates, these fibers were advantageously fermented to propionate, at least to some extent, in all subjects. Glucose alone, as a galactomannan polysaccharide, exhibited high propionate production rates, but with high inter-individual variability, and propionate production by the microbiota of some of the donors in Example 1 was completely absent. In addition to their excellent ability to be metabolized to propionate, galactomannan polysaccharides and partially hydrolyzed galactomannans are characterized by good butyrate production rates and limited inter-individual variability, particularly for galactomannan polysaccharides. This is because the microbiota of all donors were capable of butyric acid production upon fermentation of galactomannan polysaccharides and partially hydrolyzed galactomannans.

[0032] Galactooligosaccharides are polymers of galactose units formed by the polymerization of lactose, optionally with terminal glucose units. The chain length and type of linkage between the galactose units varies significantly between different galactooligosaccharide fractions, i.e., depending on the enzyme involved in the polymerization of lactose.

[0033] Galactooligosaccharides are highly advantageous because they have a high average butyric acid production rate when fermented by the microflora of diverse donors.However, galactooligosaccharides are optional in the compositions of the present invention because they may contain trace amounts of lactose, which may not be well tolerated by a small number of consumers with health problems.Therefore, this dietary fiber is omitted in compositions targeted at frail consumers or consumers with lactose intolerance.

[0034] The optional arabinoxylan and / or β-glucan source can be refined fiber or any ingredient containing such fiber, preferably a fiber composition such as oat and / or wheat fiber. Both arabinoxylan and β-glucan have been known to have beneficial effects on improving intestinal function, improving postprandial glycemic response, and lowering blood cholesterol. Therefore, these fibers are advantageously used as essential components of the dietary fiber composition of the present invention, optionally in combination with galactooligosaccharides.

[0035] In preferred embodiments, the dietary fiber is present in the dietary fiber compositions of the present invention in the following amounts: a. the fructooligosaccharides are present in an amount of 10 to 50% by weight, preferably 10 to 40% by weight, more preferably 14 to 34% by weight, based on the total weight of the composition; b. inulin is present in an amount of 5 to 40% by weight, preferably 8 to 30% by weight, more preferably 10 to 26% by weight, based on the total weight of the composition; c. the resistant maltodextrin is present in an amount of 3 to 30% by weight, preferably 3 to 25% by weight, more preferably 5 to 20% by weight, and most preferably 5 to 15% by weight, based on the total weight of the composition; d. the resistant dextrin is present in an amount of 2 to 20% by weight, preferably 3 to 15% by weight, more preferably 4 to 12% by weight, based on the total weight of the composition; e. the galactomannan polysaccharide is present in an amount of 0.5 to 10% by weight, preferably 1 to 7% by weight, and more preferably 1 to 5% by weight, based on the total weight of the composition; f. The partially hydrolyzed galactomannan is present in an amount of 1 to 20 wt. %, preferably 2 to 15 wt. %, more preferably 4 to 13 wt. %, and most preferably 5 to 12 wt. %, based on the total weight of the composition.

[0036] If present, the optional dietary fiber is present in the following amounts: a. galactooligosaccharides are present in an amount of preferably 5 to 25% by weight, preferably 8 to 20% by weight, more preferably 10 to 15% by weight, based on the total weight of the composition; b. The at least one arabinoxylan source and / or the at least one β-glucan source preferably represent a total amount of 35 to 55% by weight, preferably 40 to 50% by weight.

[0037] When present, wheat fiber is preferably present in an amount of 15 to 35% by weight, preferably 20 to 30% by weight, based on the total weight of the composition, and oats are preferably present in an amount of 10 to 25% by weight, preferably 15 to 23% by weight, based on the total weight of the composition.

[0038] In certain embodiments, the dietary fiber compositions of the present invention comprise fructooligosaccharides, inulin, resistant maltodextrin, resistant dextrin, galactomannan polysaccharides, partially hydrolyzed galactomannans, optionally galacto-oligosaccharides, optionally an arabinoxylan source, and optionally a β-glucan source. Preferably, the dietary fiber compositions comprise such ingredients in the amounts disclosed above.

[0039] Nutritional Composition In one embodiment, the present invention relates to a nutritional composition comprising the dietary fiber composition as described above. Such a dietary fiber composition can be added to any type of nutritional composition. In particular, the nutritional composition can be in the form of a nutritional supplement, food, or beverage.

[0040] Nutritional supplements typically comprise the dietary fiber composition of the present invention together with a suitable carrier and optionally other ingredients.Nutritional supplements may be in the form of solid, liquid, or semi-solid, such as powder, liquid, paste, gel, tablet, capsule, or pastille.The supplement can be taken as is, or can be, for example, dissolved or dispersed in a liquid, sprinkled on food, or added to food or beverages.

[0041] Any liquid or solid carrier suitable for oral administration can be used.Examples of such carriers include solvents or diluents, particularly water or aqueous solutions and oils, solid organic or inorganic carriers such as gelatin, gum or talc, sugar, starch or gum arabic.The supplement may further comprise emulsifiers, dispersants or solubilizers (oils, fats, waxes, lecithins, etc.), hydrocolloids (gums, proteins, modified starches, etc.), binders, film-forming agents, encapsulating agents, wall / shell materials, coatings, adsorbents, fillers, wetting agents, flow agents, gelling agents, gel-forming agents, preservatives (antioxidants and antibacterial agents, etc.), flavoring agents, stabilizers, buffers, lubricants and / or coloring agents.

[0042] The nutritional composition may also contain additional nutrients such as macronutrients, vitamins, minerals, or probiotics. However, in certain embodiments, the nutritional composition does not contain probiotics. Indeed, since the dietary fiber composition of the present invention is designed to be compatible with the diverse types of microflora present in the consumer's gastrointestinal tract and ensure sufficient short-chain fatty acid production, the additional administration of probiotics, although possible, is not required.

[0043] The nutritional composition may also be a beverage or food product such as milk, a smoothie, a soft drink, infant formula, grow-up milk, baby food, bread, pastry, cake, breakfast cereal, cereal-based products such as muesli, granola or porridge, soup, dessert, meat or meat substitute product, etc.

[0044] The nutritional composition is typically prepared by mixing the dietary fiber composition according to the present invention with other ingredients of the nutritional composition, and is preferably packaged in a suitable manner.

[0045] Compositions for use in therapy Dietary fiber compositions can be advantageously used in therapy due to their ability to be metabolized into short-chain fatty acids upon fermentation by the microbiota of the individual consuming them, and this effect can be advantageously obtained in a wide variety of subjects with different microbiota, as demonstrated by the following examples.

[0046] The present invention therefore relates to a dietary fiber composition as described above for use in therapy, where treatment is intended to treat and / or prevent a disease or disorder and / or reduce the severity and / or symptoms of a disease or disorder.

[0047] In a preferred embodiment of the present invention, the dietary fiber composition of the present invention is for use in increasing the production rate of at least one short-chain fatty acid (SCFA) in an individual. Preferably, the at least one SCFA is butyrate, propionate, acetate, or a mixture thereof. In a more preferred embodiment, the SCFA is butyrate. More preferably, the individual is one in need of increased production of the SCFAs butyrate and / or propionate, respectively.

[0048] In other preferred embodiments, the dietary fiber compositions of the present invention are for use in providing at least one of the following therapeutic benefits: a. improving bowel function in individuals consuming a dietary fiber composition or nutritional composition; b. reducing gastrointestinal symptoms in individuals consuming the dietary fiber composition or nutritional composition; c. Increased microbiota diversity in individuals consuming the dietary fiber composition or nutritional composition; d. improving postprandial glycemic response in individuals consuming the dietary fiber composition or nutritional composition; e. Lowering blood lipids, preferably blood cholesterol, in individuals consuming the dietary fiber composition or nutritional composition; f. preventing elevated blood cholesterol levels in individuals consuming the dietary fiber or nutritional composition; g. A reduction in blood glucose levels, preferably a reduction in glycated hemoglobin levels, more preferably a reduction in HbA1c levels, in an individual consuming the dietary fiber composition or nutritional composition; h. Prevention of an increase in blood glucose levels, preferably prevention of an increase in glycosylated hemoglobin levels, more preferably prevention of an increase in HbA1c, in an individual ingesting a dietary fiber composition or a nutritional composition; preferably prevention of an increase in blood glucose levels, preferably prevention of an increase in glycosylated hemoglobin levels, more preferably prevention of an increase in HbA1c, in an individual diagnosed with prediabetes and ingesting a dietary fiber composition or a nutritional composition; even more preferably prevention of an increase in blood glucose levels, preferably prevention of an increase in glycosylated hemoglobin levels, more preferably prevention of an increase in HbA1c, in an individual diagnosed with prediabetes and with an HbA1c level of less than 6.0 prior to administration of the composition, and ingesting a dietary fiber composition or a nutritional composition, i. reducing blood pressure in individuals consuming the dietary fiber composition or nutritional composition; j. preventing an increase in blood pressure in an individual consuming a dietary fiber composition or nutritional composition; k. improving gut homeostasis in individuals consuming the dietary fiber composition or nutritional composition; l. improving energy metabolism in individuals consuming the dietary fiber composition or nutritional composition; m. Prevention of obesity and / or overweight in individuals consuming a dietary fiber composition or nutritional composition; n. Improved insulin sensitivity in individuals consuming the dietary fiber composition or nutritional composition, preferably in individuals diagnosed with pre-diabetes; o. preventing, treating, or reducing the severity of type 2 diabetes in individuals consuming the dietary fiber composition or nutritional composition; p. Preventing, treating, or reducing inflammation in an individual consuming a dietary fiber composition or nutritional composition; q. Enhancement of intestinal barrier function in individuals consuming the dietary fiber composition or nutritional composition; r. Enhancement of mucosal immunity in individuals consuming the dietary fiber composition or nutritional composition; s. preventing, treating, or reducing the severity of an infectious disease, such as a viral, bacterial, or fungal infection, in an individual consuming the dietary fiber or nutritional composition; t. Enhancement of bidirectional communication between the central nervous system and the enteric nervous system (gut-brain axis) in individuals consuming the dietary fiber composition or nutritional composition; u. preventing or reducing the severity of autism-spectrum, anxiety and / or depressive behaviors in individuals consuming the dietary fiber composition or nutritional composition; v. preventing, treating and / or reducing the severity of irritable bowel syndrome in individuals consuming the dietary fiber composition or nutritional composition; w. reduction of stress, preferably reduction of stress perception, in individuals consuming the dietary fiber composition or nutritional composition; and / or x. Reduction of fasting blood insulin levels in individuals consuming the dietary fiber or nutritional composition, preferably in individuals diagnosed with pre-diabetes.

[0049] In preferred embodiments, the therapeutic effect is achieved as a result of an increased rate of SCFA production in an individual consuming the dietary fiber or nutritional composition, and indeed, it has been established in the prior art that SCFA production, and in particular butyrate production, is associated with such therapeutic effect.

[0050] In other words, the present invention relates to a method of treatment comprising administering a dietary fiber composition or nutritional composition according to the present invention to a subject in need thereof. In a preferred embodiment, the method of treatment is for increasing the production rate of at least one short-chain fatty acid (SCFA) in an individual. Preferably, the at least one SCFA is butyrate, propionate, acetate, or a mixture thereof. In a more preferred embodiment, the SCFA is butyrate. In another preferred embodiment, the method of treatment is for providing at least one of the above-mentioned therapeutic effects.

[0051] In other words, the present invention relates to the use of the dietary fiber composition or nutritional composition according to the present invention in therapy. Preferably, the use is for increasing the production rate of at least one short-chain fatty acid (SCFA) in an individual. Preferably, the at least one SCFA is butyrate, propionate, acetate or a mixture thereof. In a more preferred embodiment, the SCFA is butyrate. In another preferred aspect, the use is for providing at least one of the above-mentioned therapeutic effects.

[0052] In other words, the present invention relates to the use of a dietary fiber composition or nutritional composition according to the present invention for the manufacture of a medicament. In a preferred embodiment, the medicament is for increasing the production rate of at least one short-chain fatty acid (SCFA) in an individual. Preferably, the at least one SCFA is butyrate, propionate, acetate, or a mixture thereof. In a more preferred embodiment, the SCFA is butyrate. In another preferred embodiment, the medicament is for providing at least one of the above-mentioned therapeutic effects.

[0053] In a preferred embodiment, the dietary fiber or nutritional composition of the present invention is administered in a therapeutically effective amount, preferably at a dose of at least 5 g, preferably 5-30 g of dietary fiber composition per day.

[0054] There is no limit to the administration period of the dietary fiber composition according to the present invention. It is advantageous to take the dietary fiber composition or nutritional composition for a long period of time in order to obtain the above-mentioned benefits over a long period of time. However, even a short-term administration scheme can be beneficial. For optimal effect, it is preferred that the dietary fiber composition or nutritional composition be administered for a period of at least 1 week, preferably at least 2 weeks, preferably at least 3 weeks, preferably at least 1 month, more preferably at least 2 months, and most preferably at least 3 months.

[0055] In certain embodiments, the individual is in need of any one or more of the above therapeutic effects.

[0056] In a preferred embodiment, the individual has symptoms of prediabetes and / or is overweight or obese. More preferably, the individual with symptoms of prediabetes has not been clinically diagnosed with diabetes. In a preferred embodiment, the individual with symptoms of prediabetes is characterized by a hemoglobin A1C of greater than 6.0% within the past 12 months, more preferably 6.0-6.5%, and most preferably 6.0-6.4%.

[0057] In another preferred embodiment, the individual does not suffer from severe liver disease such as chronic persistent hepatitis, cirrhosis and / or the co-occurrence of positive hepatitis B virus surface antigen and abnormal liver transaminases (serum concentrations of alanine transaminase or aspartate transaminase >2.5 times the upper limit of normal).

[0058] In another preferred embodiment, the individual does not suffer from a microbiota disorder, or if the individual suffers from a microbiota disorder, the nutritional composition that the individual ingests further comprises at least one probiotic.In one embodiment, the individual suffering from a microbiota disorder is an individual who is receiving a treatment that is known to damage the microbiota.The treatment that is known to damage the microbiota is, for example, as follows: a) Use of antibiotics for more than 3 days within the 3 months prior to administration b) Use of weight loss medication within the last month, preferably within the last two months, more preferably within the last three months prior to administration; c) Having undergone gastrointestinal surgery (excluding appendicitis or hernia surgery) within the last month, preferably within the last two months, more preferably within the last three months prior to administration; d) Use of medication to treat cholecystitis, peptic ulcer, urinary tract infection, acute myelitis, urinary tract cystitis or hyperthyroidism.

[0059] In another preferred embodiment, the individual does not suffer from pituitary insufficiency, serious organic disease (including cancer, coronary heart disease, myocardial infarction or stroke), infectious disease (including pulmonary tuberculosis and AIDS), significant dyslipidemia and / or hypertension above 160 / 100. [Example]

[0060] Example 1: Evaluation of the fermentation capacity of different individuals Materials and Methods 1. Experimental determination of fermentation capacity Volunteer Recruitment Whole fecal samples were collected from volunteers using a fecal collection hat and processed within 4 hours of defecation. Volunteers were given the option to either provide the sample directly at the laboratory or request a home sampling kit and schedule delivery that morning. A total of N = 71 volunteers were recruited.

[0061] Sample processing Samples were homogenized into fecal slurry by diluting 2.5-fold with L-cysteine-reduced PBS buffer, homogenizing, and filtering using WhirlPak filter bags. An aliquot from the fecal slurry was taken for DNA sequencing, and the remainder was aliquoted onto a 96-well plate. Individual wells were then further diluted 2-fold by adding either the control condition (i.e., PBS buffer) or the relevant spike-in (dietary fiber dissolved in L-cysteine-reduced PBS buffer) to a final spike-in concentration of 10 g / L. The different spike-ins were fructooligosaccharides, galactooligosaccharides, gum arabic, inulin, resistant maltodextrin, resistant dextrin, oat fiber, partially hydrolyzed guar gum, glucose, fructose, wheat fiber, pectin, nopal cactus fiber, galactomannan, psyllium husk, cellulose, chitosan, and microchitosan. Two separate 500 μL samples (from separate wells, constituting biological replicates) are taken at 0, 2 and 4 hours and frozen at −80° C. for subsequent analysis.

[0062] GC-FID measurement The samples were removed from the freezer and allowed to thaw. The pH of the thawed fecal slurry samples was adjusted to 2-3 with 1% aqueous sulfuric acid. The acidified samples were vortexed for 10 minutes and then centrifuged at 10,000 rpm for 10 minutes. Meanwhile, 200 μL of MeCN and 100 μL of 0.1% v / v 2-methylpentanoic acid solution were pipetted into a screw-neck vial. Upon completion of centrifugation, a 200 μL aliquot of the clear supernatant was transferred to the screw-neck vial. The tubes were shaken and analyzed by GC-FID on a PerkinElmer Clarus 500 equipped with an autosampler equipped with a flame ionization detector and hydrogen generator. A DB-FFAP column (30 m, 0.250 mm diameter, 0.25 μm film) was used for analyte separation. The temperature gradient used was as follows: 100°C for 5 min, then increased to 200°C over 10 min, followed by 5 min at 200°C (total run time 20 min). The concentration of each short-chain fatty acid was calculated from the ratio of the signal intensity of each SCFA peak to the signal intensity of an internal standard of known concentration. The SCFAs measured were acetate, propionate, butyrate, iso-butyrate, valerate, iso-valerate, caproate, isocaproate, and hexanoate.

[0063] Data QC Each GC-FID analytical batch was quality controlled by the following methods: (i) visual inspection of the chromatograms; (ii) inspection of the internal standard (2-methylpentanoic acid) signal for large differences between samples within the batch, in which case the batch was discarded and repeated; (iii) inspection of QC samples at the beginning, middle, and end of the run consisting of samples of known SCFA concentrations (100 μM and 1 mM); and (iv) removal of specific data points / replicates where the coefficient of variation between concentration values ​​in experimental replicates for a particular SCFA (after correction for the internal standard) exceeded 20%.

[0064] Fermentation capacity calculation Production rates were calculated for each fiber and SCFA pair by averaging the experimental replicates for each time point and calculating the hourly production rate between the 2 and 4 hour time points.

[0065] Fiber used in the fermentation experiment The fermentable substrates and fibers tested in the fermentation experiments are as follows, along with the abbreviations used in the plots contained herein: FRUC = fructose (Sigma; N = 54); GOS = galactooligosaccharides (Tate & Lyle; N = 27); GUM = gum arabic (Carl Roth; N = 66); MALT = resistant maltodextrin (Fibersol-2; N = 65); NUTR = resistant dextrin (Roquette; N = 64); OAT = oat fiber (Sanacel; N = 36); ORGR = Orafti GR fructooligosaccharide and inulin mixture (Beneo; N = 4); ORHP = Orafti HP fructooligosaccharide and inulin mixture (Beneo; N = 4); ORIN = Orafti inulin (Beneo; N = 4); ORSY = Orafti sybergy fructooligosaccharide and inulin mixture (Beneo; N = 4); PHGG = partially hydrolyzed guar gum (Sunfiber AG; N=65); WHT=wheat fiber (Sanacel; N=34); PECT=pectin (Carl Roth; N=28); GALA=galactomannan (; N=6); MCHI=microchitosan (Nutricology; N=5); NOPA=nopalcactus fiber (Seagate; N=6); PSYL=psyllium husk (Solgar; N=6); CELL=cellulose (Nutricology; N=3); CHIT=chitosan (Unsure; N=3); GLUC=glucose (Sigma; N=3).

[0066] 2. Microbiome Sequencing Aliquots from the original fecal slurry were dissolved in a nucleic acid stabilizing buffer and sent for 16S rRNA sequencing using a 16S rRNA sequencing kit from Carbiotix AB (Lund, Sweden). The resulting FASTQ sequencing files were stored in our database for future analysis.

[0067] 3. Plasma SCFA analysis Sample processing Plasma was deproteinized by adding 20.4 μL of 1 mM hexanoic acid-d11 to a 200 μL aliquot, followed by 800 μL of acidified MeCN (MeCN + 0.1% formic acid). The solution was vortexed vigorously and centrifuged at 10,000 rpm for 10 minutes at 4°C. A 250 μL aliquot of the clear supernatant was transferred to an Eppendorf tube. Derivatization was then performed by adding 250 μL of a stock solution containing 379.2 mg of 3-nitrophenylhydrazine (3-NPH), 115.1 mg of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDCi), and 300 μL of pyridine in 20 mL of 50% aqueous MeCN, followed by incubation at 40°C for 30 minutes. A 500 μL aliquot was transferred to a screw-neck vial for LC-MS analysis.

[0068] SCFA quantification by LC-MS LC-MS analysis of derivatized plasma samples was performed on an Acquity UPLC I-class system (Waters) coupled to a Xevo TQ-S micromass spectrometer (Waters) equipped with an electrospray ionization (ESI) source and operated in negative ion mode. A Waters BEH C18 UPLC column (2.1 x 100 mm, 1.7 μm) equipped with a VanGuard Pre-Column 3 / Pk was used for liquid chromatographic separation of the analytes, using water:formic acid (100:0.01, v / v, solvent A) and acetonitrile:formic acid (100:0.01, v / v, solvent B) as the mobile phases for gradient elution. The gradient elution protocol used was 5% to 65% B in 7.5 min, 65% to 95% B in 0.1 min, followed by a 3-min hold at 95% B. Between injections, the column was equilibrated at 5% B for 2.5 min.

[0069] Results: Fermentation ability of different individuals Measuring the fermentation capacity of individuals involved calculating the production rate of each SCFA from each fiber spike-in (see Methods). Figures 1 and 2 show the average production rates of butyrate and propionate, respectively, which are considered the most important SCFAs given their most important health benefits. Error bars represent standard deviations as a measure of interindividual variance.

[0070] Example 2: Dietary fiber composition according to the present invention Three different compositions of dietary fiber compositions according to the present invention are provided in Table 1 below.

[0071] [Table 1]

[0072] Composition 1 was designed as an immunomodulator and focused on IBD patients. To optimize the composition's anti-inflammatory properties, it was designed by combining fibers with the highest butyrate yields across different individuals. It does not contain insoluble fiber or GOS (which, while highly fermentable, contain high amounts of lactose, which can induce lactose intolerance-induced inflammation).

[0073] Composition 2 is designed as a metabolic regulator and combines soluble, insoluble, and fermentable fiber with an optimized fermentation profile to boost butyrate and propionate production, in addition to the health claims already available for EFSA insoluble dietary fiber (WHT and OAT).

[0074] Composition 3 is designed as a blend to improve mental health. It combines the benefits of insoluble fiber with soluble fermentable fiber. It does not contain any GOS (containing lactose) to avoid lactose intolerance-inducing irritation.

[0075] In all cases, fermentability was optimized by taking a weighted average of the fermentable fibers in question (weighted proportionally to their average SCFA production rate) after relevant constraints were introduced (e.g., inclusion of WHT and OAT insoluble fibers in the relevant amounts to obtain the relevant EFSA health claim).

[0076] Example 4: Validation of in vivo methods for assessing SCFA production The following protocol was used to assess plasma SCFA pharmacokinetics and to assess whether the compositions of the present invention were actually fermented to SCFAs in subjects.

[0077] Because existing techniques cannot directly measure SCFA production in vivo, many studies use the concentrations of SCFAs present in fecal samples collected from fiber intervention study participants as an indicator of the amount of SCFAs produced in the intestines of these same participants, but these data are inaccurate at best. Notably, fecal SCFA concentrations depend on the balance between the amount of SCFAs produced and the amount of SCFAs absorbed by the host.

[0078] To rigorously study the underlying fermentation processes in an in vivo cohort and to measure the effect of our mixture on SCFA production in clinical trials, plasma SCFAs were measured here. Because SCFAs are detectable in plasma, but at much lower concentrations, we developed a sensitive LC-MS quantification method for SCFAs (see Methods).

[0079] This method was applied to blood samples taken every 20 minutes (for the first 8 hours) and then every hour (for the next 16 hours) after consuming specific meals. N=3 study participants repeated the following meals: a. High-fiber Mediterranean diet b. A high-fat and high-sugar junk food diet c. Meal B + 20 g fiber supplement (choice between inulin, resistant maltodextrin, and resistant dextrin, depending on the patient's fermentation capacity, determined using the ex vivo method described in Example 1)

[0080] Each meal was preceded by a 12-hour fasting period, followed by 24 hours of blood sampling without further food intake.

[0081] The results are shown in Figures 6 and 7. The accumulation of SCFAs in the blood is clearly visible. A spike in butyrate can be observed after meal A (high-fiber Mediterranean diet) for participants 1 and 3, and after meal C (junk diet with fiber supplement) for participant 2 (Figure 7). These data indicate that plasma SCFAs are a valuable clinical endpoint and a good proxy for measuring SCFA production in real time to test clinical responses to our fiber mixture.

[0082] Example 5: Clinical Trials Method: Research design This study was a two-arm, individually randomized, single-blind, placebo-controlled clinical trial using an equal ratio. The study was approved by the Berkshire B NHS Human Research Ethics Committee (reference number: 22 / SC / 0363). The study was registered with ClinicalTrials.gov (registration number: NCT05593926).

[0083] Methods: Study population Written informed consent was obtained from all participants in accordance with the Declaration of Helsinki. Individuals with a primary diagnosis of prediabetes but no treatment for type 2 diabetes were recruited from two clinics in London. Inclusion criteria were men and postmenopausal women aged 18–70 years, able to provide informed consent, a body mass index (BMI) of 25 kg / m² or greater, a baseline HbA1c (glycosylated hemoglobin) between 5.8% (40 mmol / mol) and 6.5% (48 mmol / mol) within the past 12 months, willingness to complete the study requirements, and access to a smartphone or computer. Exclusion criteria were taking medication for type 1 or type 2 diabetes in the past 6 months, BMI > 45 kg / m2, weight loss of > 5% in the last 3 months, participating in a weight loss program or planning one within the next 16 weeks, steroid use (excluding over-the-counter NSAIDs, topical steroids, and inhalers), severe liver disease, antibiotic use for ≥ 3 consecutive days within the 4 weeks prior to enrollment, continuous use of weight loss medication within 3 months of study enrollment, gastrointestinal surgery (excluding appendicitis or hernia surgery or coexisting pathology (Crohn's disease, celiac disease, endometriosis, prostate cancer)), and previous surgery prior to enrollment. Participants were excluded from the study if they had: serious psychiatric illness within the past 6 months; cholecystitis, peptic ulcer disease, urinary tract infection, acute myelitis, urinary tract inflammation, or hyperthyroidism; pituitary dysfunction; serious organic disease including cancer; coronary heart disease, myocardial infarction, or cerebral apoplexy; infectious disease including pulmonary tuberculosis and AIDS; a history of alcoholism or substance misuse; significant dyslipidemia; severe hypertension (>160 / 100 mmHg); or use of any nutritional supplements to control blood glucose (e.g., chromium picolinate) within 2 months of study enrollment. Eligible participants were identified through GP practices and via social media campaigns. Participants were excluded from the study if they initiated medications used to control prediabetes.

[0084] Method: Intervention Consented participants who met the eligibility criteria and completed the baseline assessment were individually randomized into one of two groups using a web-based system (Sealed Envelope) in a 1:1 ratio, stratified by gender and BMI. For 24 weeks, the intervention group received 20 g / day of Composition 2, as described in Table 1, and the placebo group received 2 g / day of cellulose. Both the intervention and placebo supplements were powdered, unflavored, and provided to participants in single-serving sachets. The supplements were taken at any time of the day and consumed with water or mixed with any food or beverage (e.g., water, breakfast cereal, tea). To increase compliance, participants received daily text messages requesting them to confirm that they had taken the supplements. If they missed taking the supplements on any given day, they were prompted to provide a reason.

[0085] Method: Research measurements Participants visited a central clinic at baseline, week 16, and week 24 for blood pressure, blood samples, and an oral glucose tolerance test (ISI-OGTT) for insulin sensitivity. Fasting blood samples were obtained after participants completed a 10- to 12-hour overnight fast. For the ISI-OGTT, blood samples were collected at -15, 0, 30, 60, 90, and 120 minutes for measurement of plasma glucose and insulin concentrations. The insulin sensitivity index from the ISI-OGTT was calculated according to the formula derived by Matsuda and De Fronzo (1999), where insulin sensitivity is estimated by dividing a constant (10,000) by the square root of the product of fasting glucose (FBG) time, fasting insulin (FBI) time, mean glucose (MG) time, and mean insulin (MI): ISI-OGTT = 10,000 / (FPG*FPI)(MG*MI). This index correlates strongly with insulin sensitivity derived using the euglycemic clamp technique ( Matsuda & De Fronzo, 1999 ).

[0086] Methods: Primary and secondary endpoints The primary endpoint was the change in HbA1c from baseline to week 16. Key secondary endpoints included the change from baseline to weeks 16 and 24 in insulin sensitivity (measured using ISI-OGTT), FBI, blood lipids (cholesterol [total, LDL, HDL], triglycerides), inflammatory biomarkers (IL-6, IL-8, IL-10, CRP, TNF-α), and diastolic and systolic blood pressure.

[0087] Methods: Tolerability and safety Participants were asked to record whether they had experienced any side effects or medical events since starting the intervention or placebo via an online survey at the end of weeks 1–4 and monthly for the remainder of the study. If they answered "yes," the adverse event was documented, reported, and reviewed for relevance and predictability within 24 hours.

[0088] Method: Statistical analysis Data were analyzed using Python software. Statistical analysis was performed based on an intention-to-treat protocol. For the primary outcome, unpaired t-tests were used to compare the percent change in HbA1c levels from baseline to 16 weeks between the intervention and placebo groups. A two-way repeated-measures ANCOVA with one within-subject factor (time) and one between-subject factor (randomization) was used to compare secondary outcomes at baseline, 16 weeks, and 24 weeks, including HbA1c, insulin sensitivity, fasting blood insulin, lipid profile (total cholesterol, LDL, HDL, triglyceride levels), inflammatory biomarkers (IL-6, IL-8, IL-10, CRP, and TNF-α), and diastolic and systolic blood pressure. To compare differences between groups over time, post-hoc one-tailed paired t-tests were performed for significant main or interaction effects. For non-normally distributed outcome variables, robust ANCOVA and post-hoc comparisons using trimmed means were used. Subgroup analyses included the effect of baseline HbA1c levels on the primary and secondary endpoints. Effects with a p-value <0.05 were considered statistically significant.

[0089] result The results are shown in Figure 4. A parametric t-test showed a significant reduction in fasting blood insulin levels (p=0.04) and a significant improvement in insulin sensitivity (p=0.03) in participants who consumed the fiber composition of the present invention. HbA1c (%) in participants with low baseline HbA1c levels (<6.0%) was significantly lower in participants who consumed the fiber composition of the present invention (p=0.009).

[0090] Example 6: Real-World Microbiome Kit Data from Customers Methods: Collection and processing of fecal samples Volunteer customers who purchased a microbiome test kit in accordance with the applicant's terms of use were included in this analysis. Participants were provided with a stool sampling kit for home use, including a sample collection tube containing a nucleic acid stabilizing buffer, a sample swab, and instructions. The samples were then processed as follows: Fecal DNA extraction was performed by homogenizing the sample (3000 rpm, 2 minutes), after which 200 μL of sample was removed and subjected to DNA extraction on a Kingfisher Flex 96 system (origin: Thermo Fisher Scientific). Primers targeting the V4 region of the 16S gene were used. 16S rRNA sequencing was performed on an Illumina MiSeq platform.

[0091] Methods: 16S data processing and analysis Demultiplexed fastq files were processed using default settings in QIIME2 2020.2 (https: / / qiime2.org) (37). Amplicon sequence variants (ASVs) were generated by denoising with DADA2. For taxonomic structure analysis, taxonomy was assigned to ASVs using a pre-trained Naive Bayes classifier and the q2-feature classifier plugin against the Silva 16S rRNA gene sequencing database. Samples were rarefied to a read depth of 10,000 for diversity analysis. ANCOVA (analysis of covariance) was used to test for group differences in the Shannon diversity index and the Chao1 index, accounting for the influence of body mass index (BMI). Groups were compared using the qiime2 plugins PERMANOVA (permutational multivariate analysis of variance) and adonis, using beta diversity assessed using unweighted UniFrac distances (Pac Symp Biocomput. 2012:213-224). Significant features were corrected for multiple comparisons using the Benjamini-Hochberg FDR procedure, and corrected values ​​of p<0.05 and q<0.25 were considered statistically significant.

[0092] Methods: Statistical tests Data were analyzed using R software. Statistical analyses were performed based on an intention-to-treat analysis. However, as a sensitivity analysis, the primary and secondary endpoints were analyzed using the per-protocol population to investigate whether conclusions were sensitive to assumptions regarding patterns of missing data. Group differences in baseline characteristics were assessed using χ tests and parametric t-tests for categorical variables or Wilcoxon signed-rank tests for quantitative variables. All comparisons were tested for normality and homosedism. Differences between groups were analyzed by two-way repeated-measures ANOVA assessing the main effects of time and treatment. If the main effect or interaction (time × treatment) was significant (p<0.05), within-group analyses were performed using Tukey's post-hoc test.

[0093] result The results are shown in Figure 5.

[0094] Wilcoxon signed rank tests identified significant differences in Shannon diversity (p=0.007) and richness (p=0.03) between participants who consumed 300 g (or a fraction of such a dose) of Composition 2 as described in Table 1 within the three months prior to submitting a fecal sample (dark grey) compared to participants who did not (light grey).

[0095] The relationship between intake of the fiber blend of the present invention and microbial abundance (collapsed at the genus level) was assessed using the multivariate statistical framework MaAsLin2 implemented in R. Features were included if they had at least 10% non-zero values ​​(across samples) and a minimum relative abundance threshold of 0.0001, both of which validated the parameter settings in MaAsLin2. Significant features were corrected for multiple comparisons using the Benjamini-Hochberg FDR procedure, and corrected coefficient values ​​of p<0.05 and q<0.25 were considered statistically significant. Figure 5 shows that significant differences in microbiota diversity were observed between participants who consumed the fiber blend of the present invention and those who did not.

[0096] Example 7: Prebiotic Interventions for Metabolic and Mental Health Methods: Study design and participants This study was part of a larger 12-week, open-label, parallel randomized controlled trial comparing a control group receiving only healthy dietary advice with an intervention group receiving both healthy dietary advice and a multimodal prebiotic supplement in free-living MetS survivors. Analyses conducted in this study were based on secondary outcomes from a submitted ethics protocol. The study was approved by the NHS Human Research Ethics Committee of City and East (reference number: 23 / LO / 0515). Participants provided written informed consent in accordance with the Declaration of Helsinki. Briefly, individuals recruited for this study had at least three symptoms consistent with MetS but were not receiving pharmacological treatment for their condition. Participants were randomly assigned to either the prebiotic fiber intervention or the control group. Prebiotic supplements have not been formally studied in cohorts of participants with MetS. Therefore, including more participants in the prebiotic group (2:1) would provide more information about associated potential tolerance and side effects while controlling for practical purposes for cohort size.

[0097] Methods: Prebiotic intervention The prebiotic fiber group received 10 g of Composition 1 per day, as described in Table 1. The prebiotic supplement was powdered and unflavored and provided to participants in 300 g packets containing a 30-day supply. A 10 g scoop was included in each packet, and participants were advised to take one level scoop once daily at any time during the day. Participants could mix the supplement with water or stir it into food or beverages (e.g., breakfast cereal, coffee, tea). To minimize participant dropout and ensure consistent use of the supplement, participants were surveyed weekly and asked to confirm that they had taken the supplement every day that week. If they missed taking the supplement on any given day, they were prompted to provide a reason.

[0098] Methods: Dietary recommendations Both the intervention and control groups were given dietary advice before the 12-week intervention period. Dietary recommendations were provided to participants in written form and were aligned with the Heart UK "Healthy Eating Guide" (https: / / www.heartuk.org.uk / downloads / health-professionals / publications / healthy-eating-guide.pdf). Briefly, these recommendations emphasized a Mediterranean diet rich in fruits, vegetables, and healthy fats (omega-3 fatty acids), while reducing refined sugars, salt, processed foods, and alcohol intake.

[0099] Methods: General demographics, dietary fiber intake, and gastrointestinal symptoms survey At baseline and week 12, participants answered questions regarding general demographics and health status, daily dietary fiber (16-item Fiberscreen), and gastrointestinal symptoms (Gastrointestinal Symptom Rating Scale, GSRS).

[0100] Methods: Neurocognitive assessment Neurocognitive assessment included the Hamilton and Montgomery Anxiety Scale (HAM-A), Generalized Anxiety Disorder (7 items) (GAD-7), Patient Health Questionnaire (PHQ), and Depression, Anxiety, and Stress Scale (42 items) (DASS-42).

[0101] Methods: Blood sample collection and processing At baseline and week 12, participants completed a finger-prick blood test. A finger-prick blood sampling kit was shipped to the participant's chosen address with written instructions for proper use. Blood samples were collected after a minimum of 8 hours of fasting. Participants returned the samples in the mail using prepaid envelopes. Serum separator tubes (SSTs) were centrifuged to separate the serum in the samples for testing. Hs-CRP profiles were tested via the Roche Cobas c503 platform.

[0102] Methods: Statistical tests Data were analyzed using R software. Statistical analysis was based on an intention-to-treat analysis. Group differences in baseline characteristics were assessed using the χ2 test and parametric t-test for categorical variables or the Wilcoxon signed-rank test for quantitative variables. For all comparisons, we tested for normality and homosedism. Differences between groups were analyzed by two-way repeated-measures ANOVA assessing the main effects of time and treatment. If the main effect or interaction (time × treatment) was significant (p<0.05), within-group analysis was performed using Tukey's post-hoc test.

[0103] result The results are shown in Figure 6. Two-way repeated measures ANOVA showed that the susceptibility stress score (PSS) (F (1,87) =6.34, p corr =0.01) and Gastrointestinal Symptom Rating Scale (GSRS) scores (F (1,87) =9.81, p corr A significant main effect of treatment was identified for the PSS (p = 0.002). Tukey's HSD post-hoc test revealed a significant main effect of treatment for the PSS (p corr =0.04) and GSRS (p corr = 0.02) at 12 weeks, and for the intervention, a significant difference was identified between the intervention and control groups in PSS scores at baseline and 12 weeks (p corr A significant difference was identified between the two groups (p < 0.01), with the intervention group having lower scores. These results demonstrate the efficacy of the fiber blend of the present invention in reducing stress and gastrointestinal symptoms.

Claims

1. The following dietary fiber: a. isolated fructooligosaccharides (FOS), b. Isolated inulin; c. isolated resistant maltodextrin; d. isolated resistant dextrin; e. an isolated galactomannan polysaccharide, and f. Isolated Partially Hydrolyzed Galactomannan A dietary fiber composition comprising a mixture of:

2. a. the fructooligosaccharides are present in an amount of 10-50% by weight, preferably 10-40% by weight, and more preferably 14-34% by weight, based on the total weight of the composition; b. inulin is present in an amount of 5 to 40% by weight, preferably 8 to 30% by weight, more preferably 10 to 26% by weight, based on the total weight of the composition; c. the resistant maltodextrin is present in an amount of 3 to 30% by weight, preferably 3 to 25% by weight, more preferably 5 to 20% by weight, and most preferably 5 to 15% by weight, based on the total weight of the composition; d. the resistant dextrin is present in an amount of 2 to 20% by weight, preferably 3 to 15% by weight, and more preferably 4 to 12% by weight, based on the total weight of the composition; e. the galactomannan polysaccharide is present in an amount of 0.5 to 10% by weight, preferably 1 to 7% by weight, and more preferably 1 to 5% by weight, based on the total weight of the composition; f. The dietary fiber composition of claim 1, wherein the partially hydrolyzed galactomannan is present in an amount of 1 to 20% by weight, preferably 2 to 15% by weight, more preferably 4 to 13% by weight, and most preferably 5 to 12% by weight, based on the total weight of the composition.

3. 3. The dietary fiber composition of claim 1 or claim 2, further comprising isolated galactooligosaccharides, preferably in an amount of 5 to 25% by weight, preferably 8 to 20% by weight, more preferably 10 to 15% by weight, based on the total weight of the composition.

4. 4. The dietary fiber composition according to any one of claims 1 to 3, further comprising at least one arabinoxylan source and / or at least one β-glucan source, preferably in a total amount of 35 to 55% by weight, preferably 40 to 50% by weight.

5. 5. The dietary fiber composition according to claim 4, wherein the source of arabinoxylan and / or β-glucan is selected from wheat and / or oat fiber.

6. The dietary fiber composition according to any one of claims 1 to 5, wherein the galactomannan polysaccharide is guar gum, and / or the partially hydrolyzed galactomannan is partially hydrolyzed guar gum.

7. A nutritional composition comprising the dietary fiber composition according to any one of claims 1 to 6.

8. 8. The nutritional composition of claim 7 in the form of a drink, food or nutritional supplement.

9. 9. The nutritional composition of claim 7 or claim 8, wherein the nutritional composition does not contain any probiotic microorganisms.

10. 10. A method for producing a nutritional composition according to any one of claims 7 to 9, comprising the step of mixing a dietary fibre composition according to any one of claims 1 to 6 with other components of the nutritional composition.

11. A dietary fiber composition according to any one of claims 1 to 6 or a nutritional composition according to any one of claims 7 to 9 for use in therapy.

12. 12. A dietary fiber or nutritional composition for use according to claim 11, characterized in that the dietary fiber or nutritional composition is for use in increasing the rate of production of at least one short chain fatty acid (SCFA) by the gut microbiota of an individual consuming the dietary fiber or nutritional composition.

13. 13. A dietary fibre or nutritional composition for use according to claim 12, wherein said at least one SCFA is selected from acetate, propionate, butyrate and mixtures thereof, preferably butyrate.

14. The dietary fiber composition or the nutritional composition has the following therapeutic effects: a. improving bowel function in individuals consuming said dietary fiber composition or said nutritional composition; b. A reduction in gastrointestinal symptoms in individuals consuming the dietary fiber composition or the nutritional composition; c. increasing microbiota diversity in individuals consuming the dietary fiber composition or the nutritional composition; d. improving postprandial glycemic response in individuals consuming the dietary fiber composition or the nutritional composition; e. Lowering blood lipids, preferably blood cholesterol, in individuals consuming said dietary fiber composition or said nutritional composition; f. preventing elevated blood cholesterol levels in individuals consuming the dietary fiber composition or the nutritional composition; g. A reduction in blood glucose levels, preferably a reduction in glycated hemoglobin levels, more preferably a reduction in HbA1c levels, in an individual ingesting the dietary fiber composition or the nutritional composition; h. Prevention of an increase in blood glucose levels, preferably an increase in glycosylated hemoglobin levels, more preferably an increase in HbA1c levels, in individuals ingesting the dietary fiber composition or the nutritional composition; preferably prevention of an increase in blood glucose levels, preferably an increase in glycosylated hemoglobin levels, more preferably an increase in HbA1c levels, in individuals diagnosed with prediabetes and ingesting the dietary fiber composition or the nutritional composition; even more preferably prevention of an increase in blood glucose levels, preferably an increase in glycosylated hemoglobin levels, more preferably an increase in HbA1c levels, in individuals diagnosed with prediabetes and ingesting the dietary fiber composition or the nutritional composition before administration of the composition, with an HbA1c level of less than 6.0, i. a reduction in blood pressure in an individual consuming said dietary fiber composition or said nutritional composition; j. preventing an increase in blood pressure in an individual consuming the dietary fiber composition or the nutritional composition; k. improving intestinal homeostasis in individuals consuming the dietary fiber composition or the nutritional composition; l. improving energy metabolism in individuals consuming the dietary fiber composition or the nutritional composition; m. preventing obesity and / or overweight in individuals consuming said dietary fiber composition or said nutritional composition; n. Improved insulin sensitivity in individuals consuming said dietary fiber composition or said nutritional composition, preferably in individuals diagnosed with pre-diabetes; o. preventing, treating or reducing the severity of type 2 diabetes in an individual consuming said dietary fiber composition or said nutritional composition; p. preventing, treating, or reducing inflammation in an individual consuming said dietary fiber composition or said nutritional composition; q. enhancing intestinal barrier function in an individual consuming the dietary fiber composition or the nutritional composition; r. Enhancement of mucosal immunity in individuals consuming the dietary fiber composition or the nutritional composition; s. preventing, treating or reducing the severity of an infectious disease, such as a viral, bacterial or fungal infection, in an individual consuming the dietary fiber composition or the nutritional composition; t. Enhancement of bidirectional communication between the central nervous system and the enteric nervous system (gut-brain axis) in individuals consuming the dietary fiber composition or the nutritional composition; u. preventing or reducing the severity of autism-spectrum, anxiety and / or depressive behaviors in individuals consuming said dietary fiber composition or said nutritional composition; v. preventing, treating and / or reducing the severity of irritable bowel syndrome in an individual consuming said dietary fiber composition or said nutritional composition; w. a reduction in stress, preferably a reduction in the perception of stress, in an individual consuming said dietary fiber composition or said nutritional composition, and / or x. A reduction in fasting blood insulin levels in individuals consuming said dietary fiber composition or said nutritional composition, preferably in individuals diagnosed with pre-diabetes.

12. A dietary fiber or nutritional composition for use according to claim 11, characterized in that it is for use in providing at least one of the following:

15. 15. A dietary fiber or nutritional composition for use according to claim 11 or claim 14, wherein the therapeutic effect is achieved by increasing the rate of production of at least one short chain fatty acid (SCFA), preferably acetate, propionate, butyrate or mixtures thereof, by the gut microbiota of an individual consuming said dietary fiber or nutritional composition.

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