WO2019170790A1

WO2019170790A1 - Yeast beta glucans

Info

Publication number: WO2019170790A1
Application number: PCT/EP2019/055631
Authority: WO
Inventors: Marco Alexander Van Den Berg; Emanuel Enzo CANFORA; Ellen Elisabeth BLAAK
Original assignee: Dsm Ip Assets B.V.; University Maastricht
Priority date: 2018-03-08
Filing date: 2019-03-07
Publication date: 2019-09-12
Also published as: EP3761995A1

Abstract

The present invention relates to yeast beta glucans for increasing the acetate concentration in the distal colon of a patient. According to another aspect, the present invention relates to yeast beta glucans for use in a method of treating or preventing a condition selected from overweight and obesity in a human or animal patient in need thereof. According to yet another aspect, the present invention relates to an alimentary product, or a food supplement, comprising yeast beta glucan and/or starch. According to another aspect the present invention relates to a method for increasing the acetate concentration in the distal colon of a patient.

Description

YEAST BETA GLUCANS

Field of the invention

The present invention relates to yeast beta glucans for increasing the acetate concentration in the colon of a patient. According to another aspect, the present invention relates to yeast beta glucans for use in a method of treating or preventing a condition selected from overweight and obesity in a human or animal patient in need thereof. According to yet another aspect, the present invention relates to an alimentary product, or a food supplement, comprising yeast beta glucan and/or starch. According to another aspect the present invention relates to a method for increasing the acetate concentration in the colon of a patient.

Background of the invention

The incidence of obesity is growing rapidly and obesity has become a major health care problem of the 21st century. Adipose tissue, skeletal muscle and the liver are major organs involved in substrate metabolism and research over the past decade revealed the presence of a strong inter-organ relationship in substrate metabolism. Therefore, functional disturbances in either of these organs can theoretically cause or contribute to the development of insulin resistance. The obese insulin resistant state is characterized by adipose tissue dysfunction, resulting in systemic lipid overflow and ectopic lipid accumulation in liver and skeletal muscle. Additionally, skeletal muscle exhibits an impaired mitochondrial function and an impaired ability to adjust lipid oxidation to lipid supply. This leads to the accumulation, altered composition and/or localization of bioactive lipid metabolites interfering with insulin action.

The gut microbiota is increasingly being recognized as an important factor in fat distribution, insulin sensitivity and glucose and lipid metabolism. Accordingly, the intestinal microbiota could play an important role in the development of obesity and diabetes. One of the important functions of the human microbiota is the fermentation of indigestible carbohydrates, i.e. dietary fiber or resistant starches. The major products of this fermentation process are short-chain fatty acids (SCFA).

Several in vivo rodent studies showed that SCFA supplementation prevented diet-induced obesity and insulin resistance. Especially, increasing the acetate availability prevents diet-induced body weight gain, counteracts adiposity, and improves glucose homeostasis and insulin sensitivity.

For, example sodium acetate (5% (w/w)) added to high-fat fed mice for 12 weeks reduced body weight gain and improved insulin sensitivity without changing food intake or physical activity (Den Besten G, Bleeker A, Gerding A, van Eunen K, Havinga R, van Dijk TH, et al. Diabetes. 2015, 64:2398-408). Another study showed that dietary supplementation of acetate (5% (w/w)) for 12 weeks to high- fat fed mice inhibited body weight gain, reduced plasma glucose and insulin concentrations, as well as reduced pro-inflammatory cytokines and chemokines (Lu Y, Fan C, Li P, Lu Y, Chang X, Qi K. Scientific Reports. 2016, 6:37589).

An acute study wherein acetate administration to both the proximal as well as the distal colon of healthy, overweight men showed that fat oxidation was significantly increased, when acetate was administered in the distal part of the colon. In contrast, no effect on energy expenditure or substrate oxidation was seen when acetate was administered in the proximal colon (Canfora EE, van der Beek CM, Jocken JWE, Goossens GH, Holst JJ, Olde Damink SWM, Lenaerts K, Dejong CHC, Blaak EE. Sci Rep. 2017, 7:2360). However, direct infusion of acetate to the distal colon via enemas is not only ethically but also practically an unwanted methodology.

So, despite all the evidence suggesting a beneficial role of increasing the systemic acetate concentrations in the distal part of the colon, there is a need for an easy and acceptable method to increase the level of acetate in the distal colon.

It was now surprisingly found that specific dietary fibers can be orally consumed and lead to an increased level of acetate in the distal colon.

Definitions

“Yeast beta-glucans” (YBG), or yeast b-glucans, is defined herein as b-D-glucose polysaccharides containing a b-I ,b-O^Iiiooeb backbone with b-I ,q-D-glucose branches which are derived from yeast cell walls.

"Resistant starch" as used herein, is defined as "the sum of starch and products of starch degradation not absorbed in the small intestine of healthy individuals" (Euresta Newsletter 1 1 .1 (1991 ). Those of ordinary skill in the art generally classify resistant starch into one of the following four different classifications: RS1 , RS2, RS3, or RS4 as defined in Brown, McNaught and Moloney (1995) Food Australia 47: 272-275.

RS1 refers to starch that is physically inaccessible that is locked within cell walls of botanical substances and therefore qualifies as resistant starch. The RS1 type of resistant starch is, for example, found in partially milled grains, seeds, and legumes.

RS2 refers to native resistant starch which are a component of starch granules such as those found in bananas (especially green bananas) and raw potatoes. Bananas and raw potatoes have relatively low gelatinization temperatures, typically on the order of about 60° C to about 80° C, which often presents substantial problems in the formulation of food products. Intragranular polymeric rearrangements that lead to an increased granular resistance to amylase digestion are also included in this category. This increased resistance could be the result of heat and/or moisture treatments or annealing of the intact granule.

RS3 refers to retrograded non-granular starch or crystalline non-granular starch, such as starch found in cooked and cooled potatoes, bread crusts, and cereals (cornflakes, for example) and starch pastes that have been extensively processed (by repeated cooking and cooling).

RS4 refers to specific starches that have been chemically modified and/or re-polymerized (which may include molecular weight reduction), such as ethers, esters, and crossbonded starches, as well as chain linkage altered dextrins, pyrodextrins, and maltodextrins.

Overweight” is defined herein as a medical condition wherein the individual has a BMI of 25 to 30 kg/m².

Obesity” is defined herein as a medical condition wherein the individual has a BMI of higher than 30 kg/m².

The term "patient" as used herein refers to an animal or human that is treatable by the present invention. The term "patient" refers to both the male and female gender unless one gender is specifically indicated. Alternatively, the present patient can be mentioned a subject.

The term "treatment", in relation a given disease or disorder, includes, but is not limited to, inhibiting the disease or disorder, for example, arresting the development of the disease or disorder; relieving the disease or disorder, for example, causing regression of the disease or disorder; or relieving a condition caused by or resulting from the disease or disorder, for example, relieving, preventing or treating symptoms of the disease or disorder.

The term "prevention" in relation to a given disease or disorder means preventing the onset of disease development if none had occurred, preventing the disease or disorder from occurring in a subject that may be predisposed to the disorder or disease but has not yet been diagnosed as having the disorder or disease, and/or preventing further disease/disorder development if already present.

The term‘alimentary product’ refers to products intended for oral consumption by a mammal, typically a human, to provide sustenance and/or satisfy nutritional requirements.

Detailed description of the invention

According to a first aspect, the present invention relates to beta glucans for increasing the acetate concentration in the distal colon of a human or animal patient, comprising a step of orally administering an effective amount of the yeast beta glucan to a human or animal patient in need thereof. Preferably, the beta glucans are yeast beta glucans. It was surprisingly found by the present inventors that addition of yeast beta glucans increases the acetate concentration in the colon of a patient, particularly in the distal colon. This is beneficial for inhibiting body weight gain or reducing body weight. Accordingly, in a preferred embodiment, the present invention relates to yeast beta glucans for use as a dietary supplement. Accordingly, in another preferred embodiment, the present invention relates to yeast beta glucans for use as a medicament. More preferably, the present invention relates to yeast beta glucans for use in a method of treating or preventing overweight, or to yeast beta glucans for use in a method of treating or preventing obesity. It is advantageous that the yeast beta glucans are bioavailable in the distal colon, even after passing the gastrointestinal tract after oral intake of the yeast beta glucans. Accordingly, in a preferred embodiment the yeast beta glucans are taken orally.

In a preferred embodiment, the present yeast beta glucans for increasing the acetate concentration in the colon of a human or animal patient, or for use in a method of treating or preventing a condition selected from overweight and obesity in a human or animal patient in need thereof, comprises the step of administering an effective amount of a yeast beta glucan to the human or animal patient in need thereof.

In a preferred embodiment, the present patient is suffering from overweight and/or obesity. In some embodiments, the obesity is prevalent obesity. In some embodiments, the obesity is prevalent abdominal obesity. In some embodiments, the obesity is new-onset obesity. In another preferred embodiment, the present patient is suffering from insufficient acetate concentration in the colon, more preferably in the distal colon.

Because obesity is associated with the onset or progression of other diseases, the present patient is in a further embodiment suffering from conditions chosen from the group of reducing complications associated with obesity including vascular disease, such as coronary artery disease, stroke, peripheral vascular disease, ischemia reperfusion, etc.; hypertension; onset and/or progression of diabetes type II; hyperlipidemia, glucose homeostasis, gastrointestinal / digestivce discomfort, irritable bowel syndrome, systemic low grade inflammation and musculoskeletal diseases. The present invention, in various embodiments, accordingly provides methods of treating or preventing these complications.

In some embodiments, the present condition is a hyperglycemic medical condition. In certain aspects, the hyperglycemic medical condition is diabetes, diabetes mellitus type I, diabetes mellitus type II, or gestational diabetes, either insulin-dependent or non-insulin-dependent. In some aspects, the invention treats the hyperglycemic medical condition by reducing one or more complications of diabetes including nephropathy, retinopathy and vascular disease. The present invention, in various embodiments, accordingly provides methods of treating or preventing these complications.

In some embodiments, the present condition or pathology is metabolic syndrome. Metabolic Syndrome, also known as metabolic syndrome X, insulin resistance syndrome or Reaven's syndrome, is typically characterized by a clustering of at least three or more of the following risk factors: (1 ) abdominal obesity (excessive fat tissue in and around the abdomen), (2) atherogenic dyslipidemia (blood fat disorders including high triglycerides, low HDL cholesterol and high LDL cholesterol that enhance the accumulation of plaque in the artery walls), (3) elevated blood pressure, (4) insulin resistance or glucose intolerance, (5) prothrombotic state (e.g., high fibrinogen or plasminogen activator inhibitor-1 in blood), and (6) pro-inflammatory state (e.g., elevated C-reactive protein in blood). Other risk factors may include aging, hormonal imbalance and genetic predisposition. According to the 2001 National Cholesterol Education Program Adult Treatment Panel (ATP III), any three of the following traits in the same individual meet the criteria for Metabolic Syndrome: (a) abdominal obesity (a waist circumference over 102 cm in men and over 88 cm in women); (b) serum triglycerides (150 mg/dl or above); (c) HDL cholesterol (40 mg/dl or lower in men and 50 mg/dl or lower in women); (d) blood pressure (130/85 or more); and (e) fasting blood glucose (1 10 mg/dl or above). According to the World Health Organization (WHO), an individual having high insulin levels (an elevated fasting blood glucose or an elevated post meal glucose alone) with at least two of the following criteria meets the criteria for Metabolic Syndrome: (a) abdominal obesity (waist to hip ratio of greater than 0.9, a body mass index of at least 30 kg/m2, or a waist measurement over 37 inches); (b) cholesterol panel showing a triglyceride level of at least 150 mg/dl or an HDL cholesterol lower than 35 mg/dl; (c) blood pressure of 140/90 or more, or on treatment for high blood pressure. For purposes herein, if an individual meets the criteria of either or both of the criteria set forth by the 2001 National Cholesterol Education Program Adult Treatment Panel or the WHO, that individual is considered as afflicted with Metabolic Syndrome.

In another preferred embodiment, the present patient is aged 15 years or older, 20 years or older, 25 years or older or 30 years or older, e.g. a patient aged from 30 to 65 years. It was found by the present inventors that the patients suffering from overweight and/or obesity benefit from the intake of yeast beta glucans. More particularly, the present patient is man. More preferably the present patient is a pre-diabetic man. Pre-diabetic man are characterized in that they suffer from plasma glucose levels from 5.6 to 7.0 mmol/L or from 6.1 to 7.0 mmol/L.

In one embodiment, the patient has a body mass index (BMI) of 25 or more, e.g. 26 or more, 27 or more, 28 or more, 29 or more, 30 or more, 31 or more, 32 or more, 33 or more, 34 or more, 35 or more, 36 or more, 37 or more, 38 or more, 39 or more or 40 or more.

In one embodiment, the patient is an adult male, typically a male of over 18 years of age, having a body mass index (BMI) of 25 or more, e.g. 26 or more, 27 or more, 28 or more, 29 or more, 30 or more, 31 or more, 32 or more, 33 or more, 34 or more, 35 or more, 36 or more, 37 or more, 38 or more, 39 or more or 40 or more.

In one embodiment, the patient is an adult female, typically a female of over 18 years of age, having a body mass index (BMI) of 25 or more, e.g. 26 or more, 27 or more, 28 or more, 29 or more, 30 or more, 31 or more, 32 or more, 33 or more, 34 or more, 35 or more, 36 or more, 37 or more, 38 or more, 39 or more or 40 or more.

In one embodiment, the patient is a juvenile or adolescent male or female, typically a male or female of under 18 years of age, having a body mass index (BMI) of 25 or more, e.g. 26 or more, 27 or more, 28 or more, 29 or more, 30 or more, 31 or more, 32 or more, 33 or more, 34 or more, 35 or more, 36 or more, 37 or more, 38 or more, 39 or more or 40 or more.

In one embodiment, the present patient is suffering from impaired fasting glucose, meaning that the patient 's plasma glucose levels during fasting are consistently above the normal range, but below the diagnostic cut-off for a formal diagnosis of diabetes mellitus. In one embodiment, the present patient has a plasma glucose level during fasting within the range of 5.5-7.0 mmol/L, preferably within the range of 5.75-7.0 mmol/L, more preferably 6.1-7.0 mmol/L. In other words, the present patient has a plasma glucose of from 6.1 to 7.0 mmol/L.

In one embodiment, the present patient has an impaired glucose tolerance. According to the criteria of the World Health Organization, impaired glucose tolerance is defined as two-hour glucose levels 7.8 to 1 1.0 mmol/L on the 75-g oral glucose tolerance test. A patient is said to be under the condition of IGT when he/she has an intermediately raised glucose level after 2 hours, but less than the level that would qualify for type 2 diabetes mellitus. In one embodiment, the patient has an impaired glucose tolerance, as evidenced by a plasma glucose level within the range of 7.0 to 1 1 .0 mmol/L on the 75-g oral glucose tolerance test, more preferably a plasma glucose level within the range of 7.8 to 1 1.0 mmol/L on the 75-g oral glucose tolerance test. Alternatively, the present patient has a plasma glucose of from 7.0 mmol/L to 1 1.0 mmol/L or 7.8 to 1 1 .0 mmol/L, preferably the present patient has a plasma glucose of from 7.0 mmol/L to 1 1.0 mmol/L on the 75-g oral glucose tolerance test or 7.8 to 1 1.0 mmol/L on the 75-g oral glucose tolerance test.

In one embodiment, the invention maybe used to improve digestive health or comfort in healthy subjects or healthy patients, such as reduce flatulence, wind, intestinal bloating, distention of the abdomen by gas, pain or abdominal cramps, rumbling, reduce sensitivity to inulin, or improve stool frequency or stool consistency or bowel function. In one embodiment, the patient may have a digestive condition such as Functional gastrointestinal disorders (FGIDs) which are diagnosed and classified using the Rome IV criteria (released in May 2016; Drossman DA, Chang L, Chey WD, Kellow J, Tack J, Whitehead WE and The Rome IV Committees. Raleigh, NC: The Rome Foundation); this includes functional bowel disorders such as functional diarrhea, functional constipation, Irritable Bowel Syndrome IBS with predominant diarrhea [IBS-D], IBS with predominant constipation [IBS-C], and IBS with mixed bowel habits.

In embodiments of the invention, the methods as described herein comprise the step of identifying a patient that is in need of receiving treatment with the compositions of the invention and/or identifying a patient suffering from or at risk of suffering from any of the conditions as described here above and/or a subject meeting any of the above-described physiological characteristics as described here above.

In a yet more preferred embodiment, the present patient has a systolic blood pressure of 100- 140mmHg and diastolic blood pressure of 60-90 mmHg.

In a preferred embodiment, the present colon is the distal colon. The inventors found that yeast beta glucans are bioavailable in the distal colon. Accordingly, in a preferred embodiment the present yeast beta glucans are for improving the bioavailability of yeast beta glucans in the distal colon of the present patient.

In another preferred embodiment, the present effective amount is effective to increase the acetate concentration of the patient’s colon, preferably the distal colon. More preferably, the present effective amount of yeast beta glucan is a daily amount of at least 0.01 g, at least 0.1 g, at least 1 g, at least 2.5 g, at least 5 g, at least 6 g, at least 7 g, at least 8 g, at least 9 g or at least 10 g. In an embodiment, the present effective amount is a daily amount of yeast beta glucan of less than 25 g, less than 20 g, less than 15 g, less than 12.5 g, less than 10 g, less than 9 g, less than 8 g, less than 7 g, less than 6 g or less than 5 g. Preferably, the present effective amount of yeast beta glucan is a daily amount within the range of 0.01 to 25 gam, 1 to 20 gram, 2.5 to 15 gram, 5 to 12.5 gram, 6 to 10 gram or 7 to 9 gram.

In a more preferred embodiment, the present yeast beta glucans are dosed three times a day, more preferably the present yeast beta glucans are dosed as a supplement to breakfast, lunch and dinner. More preferably, the present yeast beta glucans are dosed during a time period of at least 14 days.

In accordance with the invention, the treatment as defined herein, is continued for a period of at least two weeks, preferably at least 3 weeks, at least 4 weeks, at least 1 month, at least two months, at least three months, at least 4 months, at least 5 months, or at least 6 months.

In a preferred embodiment, the present invention comprises a step of diagnosing a patient with insufficient acetate concentration in the colon, preferably in the distal colon. More preferably, the present invention comprises a step of diagnosing a patient as overweight or obese. More preferably the present invention comprises diagnosing a patient as having a condition as mentioned above.

In a preferred embodiment, the present yeast beta glucans are derived from a yeast of the genera Cyberlindnera, Candida, Yarowia, Pichia, Saccharomyces. More preferably the yeast is of the species Cyberlindnera jadinii, Yarowia lipolytica, Pichia pastoris, Candida utilis, Saccharomyces cerevisiae or Saccharomyces boulardii. Even more preferably the yeast is of the species Saccharomyces cerevisiae or Saccharomyces boulardii.

Preferably, the present yeast beta glucans are in spray dried form. Hence, the present yeast beta glucans are suitable to be dosed orally, for example as a supplement in a meal. A spray dried form is advantageous in view of easy handling of the yeast beta glucans, as well as storability.

In a preferred embodiment, the present invention further comprises a step of administering an effective amount of starch, or resistant starch, to a human or animal patient in need thereof. The inventors found that co-administering a starch, or a resistant starch, with the present yeast beta glucans, or present yeast cell walls, further increases the acetate concentration in the colon of the present patient. For example, the present starch is potato starch. Alternatively, the present starch is wheat, maize, rice or cassava starch. Preferably, the present effective amount of starch is an amount which is sufficient to increase the concentration of acetate in the colon of a patient. Preferably, an amount which is sufficient to increase the concentration of acetate in the colon of a patient in comparison with the addition of yeast beta glucans to the patient without administering starch. More preferably, the amount of starch is a daily amount within the range of 0.01 to 25 gam, 1 to 20 gram, 2.5 to 15 gram, 5 to 12.5 gram, 6 to 10 gram or 7 to 9 gram. Preferably, the daily amount of starch is at least 0.1 g, at least 1 g, at least 2.5 g, at least 5 g, at least 6 g, at least 7 g, at least 8 g, at least 9 g or at least 10 g. In an embodiment, the unit dose amount of the resistant starch is less than 25 g, less than 20 g, less than 15 g, less than 12.5 g, less than 10 g, less than 9 g, less than 8 g, less than 7 g, less than 6 g or less than 5 g.

In a preferred embodiment the yeast beta glucans may be combined with Resistant Starch. Resistant starch (RS) occurs naturally in a form physically inaccessible to a-amylase (RS1 ), or as native starch that can be made accessible to the enzyme by gelatinisation (RS2), or as retrograded starch formed through a cooking and cooling process (RS3) and finally as a chemically modified starch (RS4). RS2, RS3 and RS4 are not digested by mammalian intestinal enzymes and are partly fermented in the colon and these three types are classified as Functional Fibre. Examples of commercially available resistant starch are, but not limited to, derived from corn (HI-MAIZE® 260; Ingredion, Westchester, USA), granular potato starch (AVEBE, The Netherlands), from tapioca (C* Actistar 1 1700; Cerestar, France).

As will be understood by those skilled in the art, based on the present teachings, the yeast beta glucans and the resistant starch are administered orally in the form of a single composition or, alternatively are administered simultaneously or consecutively. In embodiments wherein the yeast beta glucans and the resistant starch are administered consecutively, it is preferred that the time in between the administration of the respective components is less than 5 hours, preferably less than 4 hours, less than 3 hours, less than 2 hours, less than 1 hour, less than 30 minutes, less than 20 minutes, less than 15 minutes, less than 10 minutes or less than 5 minutes.

In a preferred embodiment, the present yeast beta glucans have a size larger than 0.3 kDa, preferably larger than 0.8 kDa, more preferably larger than 3 kDa, more preferably larger than 5 kDa, even more preferably larger than 10 kDa, even more preferably larger than 20 kDa, even more preferably larger than 30 kDa, even more preferably larger than 50 kDa, even more preferably larger than 100 kDa, even more preferably larger than 200 kDa, even more preferably larger than 500 kDa.

In another preferred embodiment, the present yeast beta glucans have a size of 0.3 to 20000 kDa, preferably a size of 0.8 to 20000 kDa, more preferably a size of 3 to 20000 kDa, or 5 to 20000 kDa, or 10 to 20000 kDa, or 20 to 20000 kDa, or 30 to 20000 kDa, or 50 to 20000 kDa. More preferably a size of 0.8 to 2000 kDa, or 0.8 to 500 kDa, or 0.8 to 100 kDa, or 0.8 to 50 kDa, or 0.8 to 30 kDa, or 0.8 to 20 kDa, or 0.8 to 10 kDa, or 0.8 to 5 kDa. Even more preferably, the present glucan fragments have a length of 0.3 to 50 kDa.

In a further preferred embodiment, the present yeast beta glucans comprise 8-1 ,3-glucan fragments and/or b-I ,q-glucan fragments. Preferably the ratio b-I ,q-glucan fragments to 8-1 ,3-glucan fragments is between 1 :20 to 1 :2, like 1 :20 to 1 :3, like 1 :20 to 1 :4, like 1 :20 to 1 :5, or 1 :20 to 1 :10, or 1 : 10 to 1 :5, like 1 :10 to 1 :4, like 1 : 10 to 1 :3, or 1 : 10 to 1 :2.

In a preferred embodiment, the present yeast beta glucans are in the form of yeast cell walls. Preferably, the present invention relates to yeast cell walls for increasing the acetate concentration in the colon of a patient. Alternatively, the present invention relates to yeast cell walls for use in a method of treating or preventing a condition selected from overweight and obesity in a human or animal patient in need thereof More preferably, the present yeast cell walls are in spray dried form.

Preferably, the present yeast cell walls are derived from yeast. Preferably, the yeast cell walls are derived from yeast cell walls by treating yeast cells to provide disrupted yeast cell walls and separating the disrupted yeast cell walls. Preferably, the present yeast cell walls are disrupted yeast cell walls. Preferably, the present yeast cell walls are not attached to a viable or reproducible yeast cell. Treating yeast cells to provide disrupted yeast cell walls may be carried out with standard techniques known in the art, like an enzymatic process with proteases and/or a physical process with milling or grinding. Basic examples of such methods, but not limited to, are given by Lowman DW, West LJ, Bearden DW, Wempe MF, Power TD, Ensley HE, Haynes K, Williams DL, Kruppa MD (PLoS One. 201 1 , 6:e27614) and Bzducha-Wrobel A, Btazejak S, Kawarska A, Stasiak-Rozahska L, Gientka I, Majewska E (Molecules 2014, 19:20941-61 ). Those trained in the art will, depending on the starting materials and target (yield, quality, concentration, etc), adjust these protocols were needed.

Preferably, the concentration of b-glucan in the present yeast cell walls is increased by treating the disrupted yeast cell walls with standard techniques known in the art, like an enzymatic process, like pH treatments, like chromatographic purification steps, and/or physical processes like centrifugation.

In yet another preferred embodiment, the b-glucan concentration in the yeast cell walls is between 5% (w/w) and 100% (w/w), such as between 10% (w/w) and 50% (w/w), or between 15% (w/w) and 50% (w/w), or between 20% (w/w) and 40% (w/w), or between 20% (w/w) and 25% (w/w) or between 40% (w/w) and 50% (w/w), or between 50% (w/w) and 100% (w/w).

Preferably, the yeast cell walls are in spray dried form. Hence, the yeast cell walls are suitable to be dosed orally, for example as a supplement in a meal. A spray dried form is advantageous in view of easy handling of the yeast cell walls, as well as storability.

In yet another preferred embodiment, the present yeast cell walls are provided in the form of particles in a size range between 0.1 and 1000 micrometer, like between 0.1 and 10 micrometer, or between 0.5 and 20 micrometer, or between 1 and 10 micrometer, or between 1 and 100 micrometer, or between 10 and 200 micrometer, or between 10 and 1000.

In a preferred embodiment the yeast cell walls can be obtained from any food grade yeast. Preferably the yeast is of the genera Cyberlindnera, Candida, Yarowia, Pichia, Saccharomyces. More preferably the yeast is of the species Cyberlindnera jadinii, Yarowia lipolytica, Pichia pastoris, Candida utilis, Saccharomyces cerevisiae or Saccharomyces boulardii. Even more preferably the yeast is of the species Saccharomyces cerevisiae or Saccharomyces boulardii.

In yet another embodiment the yeast cell walls may comprise proteins. The proteins may be in the range of 0-70% (w/w), like 1-50% (w/w), 5-40% (w/w), 10-30% (w/w), 10-45% (w/w), 10-40% (w/w), 15-35% (w/w), 20-30% (w/w). In yet another embodiment the yeast cell walls may comprise lipids. The amount of lipids may be in the range of 0-50% (w/w), like 1-40% (w/w), 4-30% (w/w), 5-25% (w/w), 6-20% (w/w), 7-15% (w/w) or 10-20% (w/w). The lipids may be, but not limited to, in the form of monoglycerides, diglycerides, triglycerides, or phospholipids. The fatty acid components of the lipids comprises both saturated fatty acids and unsaturated fatty acids.

More preferably, the present yeast cell walls comprise mannans. More preferably, the present yeast cell walls comprise 1 to 50% (w/w) mannans, more preferably 5 to 40% (w/w) mannans, most preferably 10 to 30% (w/w) mannans.

In yet a further preferred embodiment, the present yeast cell walls comprise:

(i) 10 to 40 % (w/w) glucans;

(ii) 5 to 30 % (w/w) mannans;

(iii) 20 to 50 % (w/w) protein; and/or

(iv) 5 to 25 % (w/w) lipids.

In a preferred embodiment, the present yeast cell walls are dosed in a daily amount of at least 0.01 g, at least 0.1 g, at least 1 g, at least 2.5 g, at least 5 g, at least 6 g, at least 7 g, at least 8 g, at least 9 g, at least 10 g, at least 15 g, at least 20 g, at least 25 g or at least 30 g. In an embodiment, the present yeast cell walls are dosed in a daily amount of less than 60 g, less than 50 g, less than 45 g, less than 40 g, less than 39 g, less than 38 g, less than 37 g, or less than 36. Preferably, the present effective amount of yeast beta glucan is a daily amount within the range of 0.01 to 100 gam, 10 to 50 gram, 20 to 45 gram or 25 to 40 gram.

In a preferred embodiment, the present yeast beta glucans are in the form of a composition comprising the present yeast beta glucans. Preferably, the present invention relates to a composition comprising the present yeast beta glucans for increasing the acetate concentration in the colon of a patient. Alternatively, the present invention relates to a composition comprising the present yeast beta glucans for a method of treating or preventing a condition selected from overweight and obesity in a human or animal patient in need thereof More preferably, the present composition comprising the present yeast beta glucans is in spray dried form.

In yet another preferred embodiment, the b-glucan concentration in the present composition comprising yeast beta glucans is between 5% (w/w) and 100% (w/w), such as between 10% (w/w) and 50% (w/w), or between 15% (w/w) and 50% (w/w), or between 20% (w/w) and 40% (w/w), or between 20% (w/w) and 25% (w/w) or between 40% (w/w) and 50% (w/w), or between 50% (w/w) and 100% (w/w).

In yet another preferred embodiment, the present composition comprising yeast beta glucans are in the form of particles in a size range between 0.1 and 1000 micrometer, like between 0.1 and 10 micrometer, or between 0.5 and 20 micrometer, or between 1 and 10 micrometer, or between 1 and 100 micrometer, or between 10 and 200 micrometer, or between 10 and 1000.

In yet another embodiment, the present composition comprising yeast beta glucans may comprise proteins. The proteins may be in the range of 0-70% (w/w), like 1-50% (w/w), 5-40% (w/w), 10-30% (w/w), 10-45% (w/w), 10-40% (w/w), 15-35% (w/w), 20-30% (w/w).

In yet another embodiment, the present composition comprising yeast beta glucans may comprise lipids. The amount of lipids may be in the range of 0-50% (w/w), like 1-40% (w/w), 4-30% (w/w), 5-25% (w/w), 6-20% (w/w), 7-15% (w/w) or 10-20% (w/w). The lipids may be, but not limited to, in the form of monoglycerides, diglycerides, triglycerides, or phospholipids. The fatty acid components of the lipids comprises both saturated fatty acids and unsaturated fatty acids.

More preferably, the present composition comprising yeast beta glucans comprises mannans. More preferably, the present composition comprising yeast beta glucans comprise 1 to 50% (w/w) mannans, more preferably 5 to 40% (w/w) mannans, most preferably 10 to 30% (w/w) mannans.

In yet a further preferred embodiment, the present composition comprising yeast beta glucans comprises:

(i) 10 to 40 % (w/w) glucans;

(ii) 5 to 30 % (w/w) mannans;

(iii) 20 to 50 % (w/w) protein; and/or

(iv) 5 to 25 % (w/w) lipids.

According to another aspect, the present invention relates to an alimentary product, or a food supplement, comprising the present yeast beta glucans, the present starch, the present yeast cell walls and/or the present composition comprising yeast beta glucans.

In a preferred embodiment of the invention, the alimentary product is a liquid, semi-solid or solid composition suitable for oral consumption by a mammal, typically a human, either in the form in which it is presented or after further processing, such as the addition of one more further edible components. This alimentary product is preferably a food composition, a food product, a dietetic food product, a nutraceutical, a functional food product, a medical food product, a food additive, a food supplement, an infant food product, a follow-on formula, or a food product for elderly people.

As used herein,“nutraceuticals” generally encompass foods or food products that provide health and medical benefits. Nutraceuticals are edible and may be eaten directly by humans, but are preferably provided to humans in the form of additives or nutritional supplements, e.g., in the form of tablets or capsules of the kind sold in health food stores. Hence, in an embodiment of the invention, a nutraceutical product is provided, typically a product in the form of a tablet or a capsule, comprising the yeast beta glucan and/or starch as defined herein. Alternatively, it is envisaged that the product is provided in the form of a sachet containing a powder comprising the yeast beta glucan and/or starch. Preferably, such products are provided in unit dose form, i.e. in a form wherein each tablet, capsule or powder sachet contains a unit dose, as defined herein elsewhere.

As used herein, the term‘dietetic food product’ refers to products intended to satisfy particular nutritional requirements of specific groups of the population. This category of products has gained a lot of interest over the past decades, with the Slim-fast and Modifast product lines representing very well- known examples. Such dietetic food products typically are presented in the form of snacks and meal- replacement products, wherein the consumption of such products instead of regular snacks and meals will provide certain dietary benefits, such as reduced caloric intake and/or increased intake of beneficial dietary components. The most well-known and popular examples of such dietetic food products include the snack bar type product and liquid meal-replacement products. Other examples include ready-meals, savoury snacks, bakery products and dessert-type products.

Hence, a preferred embodiment of the invention concerns a dietetic food product comprising the present yeast beta glucans, the present starch, the present yeast cell walls and/or the present composition comprising yeast beta glucans. Preferably the dietetic food product is a product selected from the group consisting of bars, such as nutritional bars, energy bars, snack bars, cereal bars, bars for diabetics etc.; liquid products, such as nutritional drinks, diet drinks, liquid meal-replacers, sports drinks and other fortified beverages; dessert-type products, such as puddings, yoghurts; savoury snacks, such as chips/ tortillas, puffed and baked snacks, crackers, pretzels, savoury biscuits; and bakery products, such as muffins, cakes, biscuits and pasta, spaghetti.

The amount of the yeast beta glucan and/or starch contained in a dietetic food product depends on the kind of food product, in particular its size and composition, as well as on the frequency and amount in which the product is or is supposed to be consumed.

In a particularly preferred embodiment of the invention, the dietetic food product is presented in the form of individually packaged single servings, wherein each serving contains at least 10 % of the amount of the average daily amount of the yeast beta glucan and/or starch as defined herein elsewhere, more preferably at least 25 % or at least 50 % of said average daily amount, more preferably 10 %, 20 %, 25 %, 30 %, 40 %, 50 %, 60 %, 70 %, 80 %, 90 % or 100 % of said average daily amount.

In a particularly preferred embodiment of the invention, the dietetic food product is presented in the form of individually packaged single servings, wherein each serving contains a unit dose as defined herein elsewhere. Hence in an embodiment, the amount of the yeast beta glucan in one serving is at least 0.1 g, at least 1 g, at least 2.5 g, at least 5 g, at least 6 g, at least 7 g, at least 8 g, at least 9 g or at least 10 g. In an embodiment, the amount of the yeast beta glucan in one serving is less than 25 g, less than 20 g, less than 15 g, less than 12.5 g, less than 10 g, less than 9 g, less than 8 g, less than 7 g, less than 6 g or less than 5 g. In an embodiment, the amount of the resistant starch in one serving is at least 0.1 g, at least 1 g, at least 2.5 g, at least 5 g, at least 6 g, at least 7 g, at least 8 g, at least 9 g or at least 10 g. In an embodiment, the amount of the resistant starch in one serving is less than 25 g, less than 20 g, less than 15 g, less than 12.5 g, less than 10 g, less than 9 g, less than 8 g, less than 7 g, less than 6 g or less than 5 g.

In an embodiment of the invention, the yeast beta glucan is present in an amount of at least 0.1 wt.%, based on the total dry weight of the dietetic food product, more preferably at least 0.25 wt.%, at least 0.5 wt.%, at least 0.75 wt.%, at least 1 wt.%, at least 1.25 wt.%, at least 1.5 wt.%, at least 1.75 wt.%, at least 2 wt.%, at least 2.25 wt.% or at least 2.5 wt.%. In an embodiment of the invention, the yeast beta glucan is present in an amount of less than 20 wt.%, based on the total dry weight of the dietetic food product, more preferably at less than 10 wt.%, less than 9 wt.%, less than 8 wt.%, less than 7.5 wt.%, less than 7 wt.%, less than 6.5 wt.%, less than 6 wt.%, less than 5.5 wt.%, or less than 5 wt.%.

In an embodiment of the invention, the starch, or resistant starch, as defined herein, is present in an amount of at least 0.1 wt.%, based on the total dry weight of the dietetic food product, more preferably at least 0.25 wt.%, at least 0.5 wt.%, at least 0.75 wt.%, at least 1 wt.%, at least 1.25 wt.%, at least 1.5 wt.%, at least 1.75 wt.%, at least 2 wt.%, at least 2.25 wt.% or at least 2.5 wt.%. In an embodiment of the invention, the starch or resistant starch is present in an amount of less than 20 wt.%, based on the total dry weight of the dietetic food product, more preferably at less than 10 wt.%, less than 9 wt.%, less than 8 wt.%, less than 7.5 wt.%, less than 7 wt.%, less than 6.5 wt.%, less than 6 wt.%, less than 5.5 wt.%, or less than 5 wt.%.

More preferably, the dietetic food product comprises the present yeast beta glucans and present resistant starch in a ratio of (w/w) within the range of 1/5 to 10/1 , preferably 1/2 to 5/1 , more preferably 1/1 to 2/1.

A particularly preferred dietetic food product, in accordance with the invention is a product in the form of an edible bar, such as a nutritional bar, energy bar, diet bar or food supplement bar, snack bar, etc., examples of which are well known to those of skill in the art.

Typically, such bars comprise binding syrup including for example glucose syrup, granulated sugar, inulin, oligofructose, glycerol, water, emulsifier, fat, flavors, and cereal components such as oat flakes, raisins and rice crisp, and yeast beta glucan and/or starch. The binding syrup may be heated along with the yeast beta glucan and/or starch with cereal components may be added once the syrup is cooled.

According to another aspect, the present invention relates to a method for increasing the acetate concentration in the colon of a patient comprising the step of treating overweightness or obesity of a patient by administering an effective amount of a yeast beta glucan or an effective amount of yeast cell walls. Preferably, the present patient suffers from insufficient acetate concentration in the colon.

Preferably, the present invention relates to a method of treating or preventing overweightness or obesity of a patient, preferably by administering an effective amount of a yeast beta glucan or an effective amount of yeast cell walls or composition comprising yeast beta glucans.

Preferably, the method further comprises the step of diagnosing a patient with insufficient acetate concentration in the colon. Preferably, the present effective amount is effective to increase the acetate concentration of the patient’s colon. Preferably, the colon is the distal colon. Preferably, the patient is overweight or obese. More preferably, the patient is aged 30 to 65 years.

More preferably, the present method further comprises the step of diagnosing a patient as overweight or obese. Preferably, the patient has a plasma glucose of from 6.1 to 7 mmol/L. More preferably, the patient has a plasma glucose of from 7.0 to 1 1.0 mmol/L. In another preferred embodiment, the method comprises administering a dose of yeast beta glucans of from 0.1 to 10 grams per 14 days. More preferably, the present effective amount of yeast beta glucan is a daily amount of at least 0.01g, at least 0.1 g, at least 1 g, at least 2.5 g, at least 5 g, at least 6 g, at least 7 g, at least 8 g, at least 9 g or at least 10 g. In an embodiment, the present effective amount is a daily amount of yeast beta glucan of less than 25 g, less than 20 g, less than 15 g, less than 12.5 g, less than 10 g, less than 9 g, less than 8 g, less than 7 g, less than 6 g or less than 5 g. Preferably, the present effective amount of yeast beta glucan is a daily amount within the range of 0.01 to 25 gam, 1 to 20 gram, 2.5 to 15 gram, 5 to 12.5 gram, 6 to 10 gram or 7 to 9 gram.

More in particular, in one embodiment, the invention provides a method of treating and/or preventing a condition or pathology, typically a method of treating or preventing obesity and/or one or more disorders or symptoms associated therewith, in a subject in need thereof, said method comprising administering to said human or animal patient the present yeast beta glucan and resistant starch, or a product comprising the yeast beta glucan and resistant starch as defined herein.

The following examples serve to illustrate the invention.

Examples

Example 1

Increased acetate concentrations in in vitro model study

The in vitro fermentation model of the colon, TIM-2, was inoculated with pooled fecal microbiota (basically as described in Kortman GA, Dutilh BE, Maathuis AJ, Engelke UF, Boekhorst J, Keegan KP, Nielsen FG, Betley J, Weir JC, Kingsbury Z, Kluijtmans LA, Swinkels DW, Venema K, Tjalsma H. Front Microbiol. 2016, 6:1481 ) samples from 14 obese, prediabetic subjects as well as from 1 1‘metabolically healthy’ subjects. The fecal microbiota was freshly sampled in and directly (within 2h) on ice and under anaerobic conditions. Next, in an anaerobic cabinet, samples were diluted 1 : 1 with dialysate, and pooled at approximately equal weight, after which glycerol was added and aliquots (30 ml/tube) were snap- frozen in liquid nitrogen.

Prior to inoculation, the 4x 30-ml aliquots were taken from the -80 freezer and thawed in a water bath at 37°C for exactly 1 hour. In an anaerobic cabinet, the microbiota from the 4 tubes were combined in 1 beaker, the same volume of pre-reduced dialysate was added, and from there divided over 4 syringes of 60 ml with each ca. 60 ml of microbiota-containing liquid. The syringes were sealed with a small flexible tube with a yellow scissor. Each TIM-2 unit was inoculated with 1 of the 4 syringes (i.e. 60 ml microbiota/d ialysate mixture). (There is only a single sample port through which TIM-2 is inoculated). After the microbiota was introduced in the unit, another 60 ml of pre-reduced dialysate was added to get to the final volume of 120 ml of the system. To simulate the conditions in the proximal region of the colon, the colon transversum and the distal part of colon, the pH was increased throughout the protocol (pH 5.8-7.0). This simulated the traffic of fibres through the colon within a 24 hours experiment (whereas the last 14 hours simulated the more distal colonic site). Mixing was done by peristaltic movements as described in Minekus, M (1998. Development and validation of a dynamic model of the gastrointestinal tract. PhD thesis, Delft University of Technology, The Netherlands).

Samples were taken for SCFA production analysis (performed at Brightlabs B.V., Venlo, The Netherlands), according to Sayago-Ayerdi SG, Zamora-Gasga VM, Venema V (Food Res Int, Available online 13 December 2017, in Press).

The yeast cell walls (YCW) (7.5 g of YCW or 7.5 g of YCW + 7.5 g of RS) were added through the sample port, after a 40-hour adaptation period. An experimental week contained the following steps:

• Monday: Start up all 4 units (pH 5.8);

• Tuesday: Feeding of Simulated ileal environment medium (SIEM) (Polzin S, Huber C, Eylert E,

Elsenhans I, Eisenreich W and Schmidt H. Appl Environ Microbiol. 2013, 79:3703-3715);

• Wednesday: 3 h starvation period + single shot of test products; Throughout the day sampling after 1 , 2, 4, 6 and 8 h;

• Thursday: 24 h after addition of shot: last sample for analysis;

• Friday: cleaning.

The fibers tested were: YCW, with and without RS2 (tapioca starch).

The increase in acetate concentration between the last two sampling points was taken as an indication for the potential increase in acetate in the distal colon:

Table 1 : increase in acetate concentration

Addition of YCW showed an increase in acetate production in the last 14-16 hours (simulating production in the distal colon).

Addition of YCW showed an additional increase in acetate production in the last 14-16 hours (simulating production in the distal colon) when RS was co-incubated, while using microbiota from healthy subjects.

Moreover, addition of YCW showed an additional increase in acetate production in the last 14- 16 hours (simulating production in the distal colon) when RS was co-incubated, while using microbiota from obese subjects. Example 2

A double blind, placebo-controlled, randomized, crossover intervention study with YGB

The study was a double blind, randomized crossover study, which allowed evaluation of the role of mixtures of indigestible carbohydrates on fecal and plasma acetate concentrations and substrate and energy metabolism in 24 male subjects. After initial screening, the subjects obtained their intervention supplement 3 times with at least 14-days washout in between. The day before each visit, participants consumed one of the supplements with standardized meals.

As study population twelve lean (BMI > 20kg/m² and < 24.9kg/m²) healthy men aged 30 - 65 years and 12 overweight/obese (BMI > 25kg/m² and < 34.9kg/m²) pre-diabetic men aged between 30 - 65 years were selected. Both groups consistent of Caucasian males, aged 30 - 65 years, with normal blood pressure (systolic blood pressure 100-140mmHg, diastolic blood pressure 60-90 mmHg) and a stable weight for at least 3 months (± 2 kg).

The intervention study was set-up as follows. The day before each visit, participants consume one of the supplements with standardized meals:

• Placebo: 1 1.43 g (3 x 3.81 g) maltodextrin Glucidex IT 12 (Roquette Freres, Lestrem, France) + 18.7 g (3 x 6.233 g) Lynside ProteYn70 (containing 70% yeast protein) (LeSaffre, Maisons- Alfort, France) and 4.58 g (3 x 1.526 g) granulated lecithin (containing 98% fat) (Bloem Health Products B.V., Winschoten, The Netherlands). The latter two being of similar type and same amounts in the evaluated YBG product (137.054 kcal/d)

• YCW: 35.294 g (3 x 1 1.753 g) Yeast Cell Walls (containing 34% yeast beta glucan (4g)) (DSM, Delft, The Netherlands) with 5.43.g (3 x 1.81 g) maltodextrin to make it isocaloric (137.054 kcal/d)

• YCW with RS: 35.294 g (3 x 1 1.753 g) YCW (34% yeast beta glucan (4g)) (DSM, Delft, The Netherlands) in combination with 9.375 g (3 x 3.125 g) granular potato starch (containing 80% resistant starch) (Avebe, Veendam, The Netherlands) (137.054 kcal/d)

All 3 products are isocaloric.

Subjects consumed the supplements with breakfast, lunch and a standardized diner by transferring the content of the sachets in a 150 ml yoghurt and consume the complete yoghurt.

As primary study parameters/endpoints the effects of acute supplementation of YCW alone or in a mixture with RS on plasma and fecal acetate availability in two different metabolic phenotypes (lean, normoglycemic vs overweight/obese, prediabetic men) were determined.

As secondary parameters, the following were determined: • Energy expenditure, fat and carbohydrate oxidation measured using an open-circuit ventilated hood system (Omnical, Maastricht University, The Netherlands);

• Circulating hormone concentrations (Insulin, GLP-1 , PYY);

• Circulating metabolite concentrations (Glucose, Free Fatty Acids, Triglycerides);

· Inflammatory markers (TNF-a, IL-6, I L- 1 b , Adipokines);

• Appetite (Visual Analog Scales (VAS)-scoring system for hunger and satiety);

• Breath H2 using (Bedfont EC60 Gastrolyzer, Rochester, UK);

• Faecal microbiota composition (16S RNA);

• Three-day food record (a three-day food record was completed three days prior to each Clinical Investigation Day, CID);

• Gastrointestinal Symptom Rating Scale (GSRS) questionnaire (this was completed the day before the CID (=the day when supplementation with the intervention products occurs), the day of the CID, and the day after the CID.

Before the three CIDs (approximately 5 hours) the subjects had a 10-hour fasting period. During baseline conditions, and after the high-fat test meal, plasma acetate concentration and markers of substrate and energy metabolism was determined. Also, energy expenditure, fat and carbohydrate oxidation (open-circuit ventilated-hood system) was assessed, venous blood was taken, H2 breath and VAS scores were assessed.

Claims

1. Yeast beta glucans for increasing the acetate concentration in the distal colon of a human or animal patient, comprising a step of orally administering an effective amount of the yeast beta glucan to a human or animal patient in need thereof.

2. Yeast beta glucans for use in a method of treating or preventing a condition selected from overweight and obesity in a human or animal patient in need thereof, comprising a step of orally administering an effective amount of the yeast beta glucan to a human or animal patient in need thereof.

3. Yeast beta glucans for use according to claim 1 or claim 2, further comprising a step of administering an effective amount of resistant starch to a human or animal patient.

4. Yeast beta glucans for use according to any one of the preceding claims, wherein the patient is suffering from a condition selected from overweight and obesity.

5. Yeast beta glucans for use according to any one of the preceding claims, wherein the patient has a plasma glucose of from 6.1 to 7.0 mmol/L.

6. Yeast beta glucans for use according to any one of the preceding claims, wherein the patient has a plasma glucose of from 7.0 mmol/L to 1 1.0 mmol/L.

7. Yeast beta glucans for use according to any one of the claims 3 to 6, wherein the resistant starch is selected from the group consisting of RS2 and RS3.

8. Yeast beta glucans for use according to any one of the preceding claims, wherein the yeast beta glucans are dosed at 0.1 to 20 grams per day.

9. Yeast cell walls for increasing the acetate concentration in the colon of a human or animal patient.

10. Yeast cell walls for use in a method of treating or preventing a condition selected from overweight and obesity in a human or animal patient in need thereof.

1 1. Yeast cell walls for use according to claim 1 1 or claim 12, wherein the yeast cell walls comprise:

(i) 10 to 40 % (w/w) glucans;

(ii) 5 to 30 % (w/w) mannans;

(iii) 20 to 50 % (w/w) protein; and/or

(iv) 5 to 25 % (w/w) lipids.

12. Alimentary product comprising yeast beta glucans and starch.

13. Dietetic food product comprising yeast beta glucans and starch.

14. A method for increasing the acetate concentration in the colon of a patient comprising the step of administering an effective amount of a yeast beta glucan to a human or animal patient in need thereof.

15. A method for increasing the acetate concentration in the colon of a patient comprising the step of treating overweightness and/or obesity of a patient by administering an effective amount of a yeast beta glucan.

16. The method of any one of the preceding claims, wherein the patient suffers from insufficient acetate concentration in the colon.

17. The method of any one of the preceding claims, further comprising the step of diagnosing a patient with insufficient acetate concentration in the colon.

18. The method of any one of the preceding claims, wherein the effective amount is effective to increase the acetate concentration of the patient’s colon.

19. The method of any one of the preceding claims, wherein the colon is the distal colon.

20. The method of any one of the preceding claims, wherein the patient is overweight or obese.

21. The method of any one of the preceding claims, further comprising the step of diagnosing a patient as overweight or obese.

22. The method of any one of the preceding claims, wherein the patient is aged 30 to 65 years.

23. The method of any one of the preceding claims, wherein the patient has a plasma glucose of from 6.1 to 7 mmol/L.

24. The method of any one of the preceding claims, wherein the patient has a plasma glucose of from 7.0 to 1 1 .0 mmol/L.

25. The method of any one of the preceding claims, comprising administering a dose of yeast beta glucans of from 0.1 to 20 grams per 14 days.

26. The method of any one of the preceding claims, comprising administering a dose of starch.