NON-THERAPEUTIC METHODS FOR MAINTAINING A HEALTHY BODY WEIGHT OR LOSING BODY WEIGHT
Patent Information
- Application Number
- MX2021014526
- Authority / Receiving Office
- MX · MX
- Patent Type
- Patents
- Current Assignee / Owner
- Priority Date
- 2019-06-17
- Filing Date
- 2021-11-26
- Publication Date
- 2026-02-25
- Estimated Expiration
- 2040-05-26
AI Technical Summary
Existing methods fail to effectively increase short-chain fatty acid (SCFA) concentrations in the distal colon of lean subjects for maintaining healthy body weight or preventing weight gain, without the use of breast milk and with minimal impact on taste and diet compatibility.
Administering 2'-fucosyl-lactose (2'-FL) and resistant starch (RS) to subjects with a lean body mass index (BMI) to enhance SCFA production, particularly acetate, in the distal colon, thereby promoting weight management and metabolic health.
The combination of 2'-FL and RS significantly increases SCFA levels in the distal colon, leading to improved fat oxidation, increased satiety hormone levels, and enhanced metabolic markers, effectively supporting weight maintenance and preventing weight gain.
Abstract
Description
NON-THERAPEUTIC METHODS FOR MAINTAINING A HEALTHY BODY WEIGHT OR LOSING BODY WEIGHT FIELD OF INVENTION The invention disclosed herein relates to non-therapeutic methods for maintaining a healthy body weight or losing body weight in a lean subject. The invention further relates to non-therapeutic methods for increasing the concentration of short-chain fatty acids (SCFAs) in the distal colon of a subject. The invention also relates to 2'-fucosyllactose and resistant starch (RS) for use in preventing overweight or a condition associated with overweight in a subject; and to a composition comprising 2'-fucosyllactose (2'-FL) and RS, and to the use of such a composition. BACKGROUND OF THE INVENTION For healthy individuals, controlling body weight is often considered important for aesthetic reasons and / or to maintain a healthy body weight and / or to lose weight. The gut microbiota has been increasingly recognized as an important factor in fat distribution, insulin sensitivity, glucose metabolism, and lipid metabolism. Consequently, the gut microbiota could play a significant role in body weight management. One important function of the human microbiota is the fermentation of dietary fibers, such as indigestible carbohydrates. The main products of this fermentation process are short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate. It has been recognized that increasing the colonic and more systemically abundant SCFAs, particularly increasing acetate levels, can prevent diet-induced body weight gain, counteract adiposity, improve glucose homeostasis and / or insulin sensitivity in rodents. Furthermore, a study in which sodium acetate was administered to the proximal or distal colon of overweight men showed that fat oxidation and circulating plasma concentrations of the satiety hormone peptide YY (PYY) increased significantly when acetate was administered to the distal colon. Conversely, no effect on energy expenditure or substrate oxidation was observed when acetate was administered to the proximal colon (van der Beek, CM, et al. Clinical Science 2016, 130(22), 2073-2082). In another study, distal colonic infusions of SCFA mixtures, all with maximum acetate content, increased energy expenditure, fat oxidation, and plasma PYY in men (Canfora EE et al., Sci Rep. 2017, 7:2360). This was confirmed by Bindels et al., who showed that distal, but not proximal, colonic acetate infusion led to changes in metabolic markers, specifically an increase in fasting fat oxidation, fasting PYY levels, postprandial glucose and insulin levels, as well as a trend toward increased fasting acetate levels. Several factors could explain the influence of the infusion site. The proximal and distal colons differ in their microbial composition, GPR43 expression profile, and drainage system, as the distal colon drains into the systemic circulation and, unlike the proximal colon, bypasses first-pass metabolism (Bindels et al. / Clin Sci (Lond) (2016) 130 (22):2083-2086 https: / / doi.org / 10.1042 / CS20160556). Therefore, SCFAs that are administered or generated in sufficient concentrations in the distal colon are associated with a beneficial effect on body weight control in a subject. US2016 / 0310514A1 refers to compositions and methods for the treatment of metabolic disorders such as obesity, obesity-induced prediabetes, and type 2 diabetes, in which the composition comprises one or more human milk oligosaccharides. It is intended for the treatment of patients suffering from obesity; not for healthy, lean subjects. It is desired that non-therapeutic methods be provided to increase the concentration of SCFAs in the distal colon of a subject. In addition, non-therapeutic methods are desired to help subjects maintain a healthy body weight or lose weight. For example, a desired non-therapeutic method might involve administering a compound, combination of compounds, and / or composition that increases the concentration of short-chain fatty acids (SCFAs) in a subject's distal colon. Furthermore, a non-therapeutic method compatible with a normal and / or healthy diet is desired. Preferably, it should not negatively affect the taste (of food) and / or mouthfeel. Other desired properties or effects of suitable non-therapeutic methods may include, but are not limited to, maintaining other signs of general health in the subject (e.g., maintaining normal blood pressure, maintaining healthy bowel movements, normal defecation, etc.), ease of preparation, ease of implementation, increased microbiota diversity, and commercial availability of the compounds, combinations, and / or compositions used. It is an objective of the present invention to provide a non-therapeutic method that better addresses at least one of the aforementioned desires. BRIEF DESCRIPTION OF THE INVENTION In one aspect, the present invention relates to a non-therapeutic method for maintaining a healthy body weight or losing body weight in a subject, characterized in that the non-therapeutic method comprises the step of administering 2'-fucosyl-lactose (2'-FL) and resistant starch RS to the subject; wherein the subject is a lean mammal, preferably a human; and wherein the method does not comprise the step of administering breast milk to the subject. In another aspect, the invention relates to a non-therapeutic method for increasing the concentration of short-chain fatty acids (SCFAs), preferably acetate, in the distal colon of a subject, for the prevention of diet-induced body weight gain or adiposity; or for the improvement of glucose homeostasis and / or insulin sensitivity, wherein the non-therapeutic method comprises the step of administering 2'-fucosillactose (2'-FL) to the subject, wherein the subject is a lean mammal, preferably a human; and wherein the method does not comprise the step of administering breast milk to the subject. In yet another aspect, the invention relates to a composition comprising (i) 2'-FL and (ii) resistant starch, for use in the prevention of overweight or an overweight-associated state in a subject, wherein the subject is a lean mammal, preferably a human. In yet another aspect, the invention relates to a use of 2'-FL and RS for maintaining a healthy body weight or losing body weight in a subject, wherein the subject is a lean mammal, preferably a human. In a further aspect, the invention relates to the use of a composition comprising 2'FL and resistant starch, for maintaining a healthy body weight or losing body weight in a subject, wherein the subject is a mammal and has a healthy weight, preferably wherein the subject is a human. DETAILED DESCRIPTION OF THE INVENTION The term treatment, in relation to a given disease or disorder, includes, but is not limited to, inhibiting the disease or disorder, e.g., stopping the development of the disease or disorder; alleviating the disease or disorder, e.g., causing the regression of the disease or disorder; or relieving a condition caused by or resulting from the disease or disorder, e.g., 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 or development of the disease if it has not already occurred, preventing the disease or disorder from occurring in a subject who may be predisposed to the disorder, or ML / a / ZUZ 1 / U14DZ0 disease but has not yet been diagnosed as having the disease or disorder and / or prevent further development of the disease / disorder if it is already present. The invention, broadly speaking, is based on the sound idea that administering 2'-fucosyl-lactose with RS to a human with a BMI below 25 kg / m² can be used to achieve one or more of the aforementioned desires. In particular, this increases the amount of short-chain fatty acids, especially acetate, in the subject's distal colon. The combination of RS and 2'-FL results in a much higher level of acetate and short-chain fatty acids. To achieve this effect with 2'-FL alone, a much larger quantity of 2'-FL would be required, making such a treatment significantly more expensive. It is believed that 2'-fucosyl-lactose in relation to the invention provides better results than other fibers known in the art. It is known that the gut microbiota can vary significantly between individuals, even within the same species. Therefore, the gut microbiota in individuals with a healthy body weight does not necessarily exhibit the same characteristics as that of an obese individual (of the same species). Put another way, the effect of administering a therapeutic agent to an obese patient is not necessarily predictive of its effects in an individual with a healthy body weight. In a first aspect, the invention relates to a non-therapeutic method for maintaining a healthy body weight or losing body weight in a subject, characterized in that the non-therapeutic method comprises the step of administering 2'-fucosyl-lactose (2'-FL) and resistant starch (RS) to the subject; wherein the subject is a lean mammal, preferably a human; wherein the method does not comprise the step of administering breast milk to the subject. In another aspect, the invention relates to a non-therapeutic method for increasing the concentration of short-chain fatty acids (SCFAs or SCFAs for short-chain fatty acid), preferably acetate, in the distal colon of a subject, wherein the non-therapeutic method comprises the step of administering 2'-fucosyl-lactose (2'-FL) and RS to the subject, wherein said subject is a lean mammal, preferably a human; and wherein the method does not comprise the step of administering breast milk to the subject. As used herein, breast milk refers to milk from the same species as the subject to whom 2'-FL and RS are administered; breast milk does not refer to milk from the same species enriched with 2'-FL and RS. It is understood that sufficient 2'-FL needs to be administered in order to achieve the desired effect. Thus, in one embodiment, the non-therapeutic method of the invention comprises the step of MA / a / ZUZI / υΊ 4DZ0 administer an effective amount of 2'-fucosyl-lactose (2'-FL) to the subject. An effective amount depends on the species. In one embodiment, the amount of 2'-FL to be administered is at least 10 mg of 2'-FL per day, preferably at least 100 mg, for example at least 1 g, more preferably at least 2 g, for example at least 3 g, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or even at least 15 g per day. The term "subject" as used herein refers to a mammalian subject (i.e., a mammal), particularly a human, that can be treated by the method of the invention. The term "subject" refers to either male or female, unless one sex is specifically indicated. According to the invention, the subject is preferably a human subject. The human subject can be of any age; for example, the human subject can be an infant, a child, an adolescent, an adult, or an elderly person. In one embodiment of the invention, the subject is a healthy subject; in another embodiment, the subject is not obese. In a further preferred embodiment, the subject is a non-obese human subject. In embodiments of the invention, the human subject is at least 18 years old, for example, at least 25, 30, or even 35. In another embodiment, the human subject is at least 55 years old, for example, at least 60 or 65. There is no particular upper limit, although in practice, the human subjects treated according to the invention will normally be no more than 100 years old, for example, no more than 95 or 90. In one embodiment, the human subject is between 18 and 65 years old, for example, between 20 and 60 or between 25 and 50. Blood sugar level is indicative of diabetes. In one embodiment, the human subject has a fasting blood sugar level below 6.1, below 6.0, below 5.9, below 5.8, below 5.7, below 5.6, or below 5.5 mmol / L. The 2-hour oral glucose tolerance test (OGTT) with a 75-g glucose intake is indicative of hyperglycemia. In one performance, the subject has a 2-hour plasma glucose level below 7.8, below 7.6, below 7.5, below 7.4, below 7.3, below 7.2, below 7.1, or below 7.0 mmol / L, as determined by the 75-g oral glucose tolerance test. The 2-hour plasma glucose level refers to the plasma glucose level two hours after glucose ingestion. Whether an individual has a healthy weight can be assessed in different ways and depends on the species. For humans, this is generally assessed by determining the individual's body mass index (BMI), which is defined as body weight in kilograms divided by height in meters squared. In a formula, BMI for a human subject is defined as: / kg \ weight (in kgj) BMI [ετϊ —- I = —---------— {Equation 1). v m- / height (in m) · A human aged 18 years or older with a BMI below 18.5 kg / m² is considered underweight. For humans aged 18 years or older, a BMI between 18.5 kg / m² and less than 25 kg / m² is considered a healthy body weight. A human aged 18 years or older with a BMI between 25 kg / m² and less than 30 kg / m² is considered overweight. A human aged 18 years or older with a BMI of 30 kg / m² or more is considered obese. The human subject aged 18 years or older, in relation to the invention, has a body mass index (BMI) of less than 25 kg / m². Such a subject is further referred to herein as a lean subject or a person of lean weight. In a preferred embodiment, the human subject (aged 18 years or older) in relation to the invention has a BMI in the range of at least 18.5 kg / m² to less than 25 kg / m², i.e., such a subject is considered to have a healthy body weight. For humans aged 2 to 18 years (children and adolescents), the BMI value obtained using Equation 1 needs to be adjusted because girls and boys develop at different rates and have different amounts of body fat at different ages. For this reason, BMI measurements during childhood and adolescence take age and sex into account. For children and adolescents aged 2 to 18, a healthy body weight is defined as a BMI value according to the values listed in Table 1. Table 1 Definition of BMI values for healthy body weight [in kg / m2] for human subjects MA / a / ZUZI / υΊ 4DZ0 Age BMI Male (Healthy Body Weight) BMI Female (Healthy Body Weight) 2 15.14-18.40 14.83-18.01 3 14.74-17.88 14.47-17.55 4 14.43-17.54 14.19-17.27 5 14.21-17.41 13.94-17.14 6 14.07-17.54 13.82-17.33 7 14.04-17.91 13.86-17.74 8 14.15-18.43 14.02-18.34 9 14.44-19.09 14.28-19.06 Age Male BMI (Healthy Body Weight) Female BMI (Healthy Body Weight) 10 14.64-19.83 14.61-19.85 11 14.97-20.54 15.05-20.73 12 15.35-21.21 15.62-21.67 13 15.84-21.90 16.26-22.57 14 16.41-22.61 16.88-23.33 15 16.98-23.28 17.45-23.93 16 17.54-23.89 17.91-24.36 17 18.05-24.45 18.25-24.69 >18 18.50-24.99 18.50-24.99 A child or adolescent with a lean body weight or a lean weight is defined as a child or adolescent with a BMI value that corresponds to a healthy body weight or a lower BMI value as defined in Table 1 for that sex and age. As used herein, a lean weight for non-human subjects is defined as a subject having a healthy weight or a mass below a healthy weight. A healthy weight is defined differently for different species, and typical values for each species are well known in the art. A lean weight means that the subject is not obese. Typically, the non-therapeutic methods of the invention are carried out for non-medical reasons, for example, for cosmetic purposes. Therefore, in one embodiment of the invention, the non-therapeutic method is for controlling weight, losing weight, reducing weight, preventing weight gain, limiting weight gain, inducing weight loss, increasing weight loss, managing weight, and / or maintaining a healthy weight in a subject as defined herein. In a particular embodiment of the invention, the non-therapeutic method is a method for losing weight within a predetermined interval, for example, for losing weight within a 12-month interval, within a 6-month interval, within a 4-month interval, within a 3-month interval, within a 2-month interval, within a 1-month interval, within a 4-week interval, within a 3-week interval, within a 2-week interval, or within a 1-week interval. As used herein, an increase in the concentration of short-chain fatty acids (SCFAs) in the distal colon of a subject refers to an increase in the combined level of acetate, propionate, and butyrate. These levels can be determined using the TIM-2 model system as known in the art and as described elsewhere herein (e.g., see the examples). An increase in SCFAs is defined as an increase of at least 10%, preferably at least 20%, more preferably at least 40%, and even more preferably at least 50%, as determined by measuring the total amount of SCFAs produced in the last 16 hours of the experiment (representing the amounts produced in the distal colon) using the TIM-2 model compared to a reference diet. As used herein, distal colon in humans refers to the descending colon (the left side of the colon) and the sigmoid colon (the S-shaped section of the colon that connects to the rectum) or the corresponding part of the colon in other mammals. The aforementioned effects on body weight and on SCFA levels can be obtained simultaneously in the method of the invention. Therefore, in one embodiment, the invention relates to a non-therapeutic method for i) maintaining a healthy body weight or losing body weight in a subject, and ii) increasing the concentration of SCFAs, preferably acetate, in the distal colon of a subject; characterized in that the non-therapeutic method comprises the step of administering 2'-fucosillactose (2'-FL) and RS to the subject; wherein the method does not comprise the step of administering breast milk to the subject; wherein the subject is a lean mammal, preferably a human. As used herein, short-chain fatty acids (SCFAs) and short-chain fatty acid (SCFA) may be used interchangeably to refer to acetate, propionate, and butyrate. In another embodiment, the subject to whom 2'-FL and RS are administered is a human aged 2 years or older, with a body mass index (BMI) equal to or lower than the upper value indicated in Table 1 for a healthy weight for the subject's age and sex. The administration of 2'-FL and RS is preferably done orally since this is the normal way to administer food. In another embodiment, the non-therapeutic method of the invention comprises the step of administering 2'-fucosyl-lactose (2'-FL) and the step of administering resistant starch. In yet another embodiment, the non-therapeutic method of the invention comprises the step of simultaneously administering 2'-FL and resistant starch. In yet another embodiment, the non-therapeutic method of the invention comprises the step of administering 2'-FL and resistant starch, wherein the 2'-FL and the resistant starch are administered sequentially, i.e., first the 2'-FL and then the resistant starch, or first the resistant starch and then the 2'-FL. ML / a / ZUZ 1 / υΊ 4DZ0 In a favorable embodiment, the non-therapeutic method of the invention comprises a step of administering 2'-fucosyl-lactose, wherein the 2'-fucosyl-lactose is contained in a composition further comprising resistant starch. Such a composition may further comprise components such as vitamins, flavorings, and coloring agents. It is believed that the combination of 2'-FL with resistant starch provides enhanced SCFA release in the distal colon. As will be understood by those skilled in the art, the benefits of the present invention can also be achieved by the sequential or simultaneous administration of 2'-FL on the one hand and resistant starch on the other, possibly in the form of two separate compositions, each comprising one of these components. Such methods, uses, and treatments are also within the scope of the present invention. It is envisaged, however, that co-administration of the combination as part of a single product composition is particularly advantageous. Without intending to be tied to the theory, the present inventors currently believe that the colonic microbiota first ferments resistant starch as an energy source. Therefore, it is believed that (more of) 2'-FL can reach the distal colon where it is fermented by other gut microbes that produce SCFAs (particularly acetate) in that region, whereby the acetate can exert beneficial effects locally and / or enter the systemic circulation, consequently causing its metabolic effects. 2'-Fucosyl-lactose (2'-FL) is an oligosaccharide, more precisely, a neutral, fucosylated trisaccharide composed of linked L-fucose, D-galactose, and D-glucose units, Fuc(a12)Gal(pi-4)Glc; CAS No. 41263-94-9. It is the most prevalent human milk oligosaccharide (HMO) naturally present in human breast milk, constituting approximately 30% of all HMOs. HMOs are non-digestible carbohydrates and are the third most abundant component in human milk after lactose and fat. More than 200 different oligosaccharides have currently been identified in human milk. Clinical trials have suggested that 2'-FL plays a key role in protecting and promoting the health of newborn infants, particularly with regard to the immune system. The addition of 2'-FL to infant formula has been shown to be safe and well-tolerated. Furthermore, 2'-FL is safe and well-tolerated for all other age groups, especially adults. Human milk molecules (HMOs) can be obtained using methods known to those skilled in the art. For example, HMOs can be purified from human milk. Individual HMOs can be further separated using methods known in the art, such as capillary electrophoresis, HPLC (e.g., high-performance liquid chromatography with high-performance liquid chromatography). MA / a / ZUZI 4DZ0 pulsed amperometric detection; HPAEC-PAD) and thin-layer chromatography. See, for example, U.S. Patent Application No. s2009 / 0098240. Alternatively, enzymatic methods can be used to synthesize HMOs. Another method for manufacturing HMOs is by biosynthesis in genetically engineered bacteria. For example, a method for preparing 2'-FL is disclosed in WO 2012 / 112777. Alternatively, 2'-FL is commercially available, for example, from FrieslandCampina, or others. 2'-FL is a dietary fiber. For most humans, there is a maximum amount of dietary fiber that can be consumed daily. The amount of 2'-FL in the composition as used in the invention also depends on the subject's body weight (i.e., mass). Thus, in one embodiment, the amount of 2'-FL in the composition as used in the invention is more than 0.1 grams. In another embodiment, this is in the range of 0.1 to 30 grams, preferably in the range of 0.5 to 25 grams, more preferably in the range of 1 to 20 grams, and most preferably in the range of 2 to 10 grams. LNnT can be considered as a dietary fiber. In one embodiment, the composition for use according to the invention does not comprise lacto-N-neotetraose (LNnT). Resistant starches can be used in the invention. Starches are polysaccharides composed of various α-D-glucose molecules linked by (1-4) and / or (1-6) bonds. Starch consists of two main structural components: amylose, which is essentially a linear polymer in which α-D-glucose residues are (1-4) linked, and which typically constitutes 15% to 20% of most starches; and amylopectin, which is a branched molecule with (1-4) and D-(1-6) linkages between the α-D-glucose units and is the major component of most starches. Starches can be classified according to their behavior when incubated with enzymes without prior exposure to dispersing agents. According to this system, starches can be classified as rapidly digestible starch (RDS), slowly digestible starch (SDS), and resistant starch (RS). The term resistant starch was first used by Englyst et al.In 1982, the term RS was coined to describe a small fraction of starch that was resistant to hydrolysis by exhaustive in vitro treatment with α-amylase and pullulanase. RS was the unhydrolyzed starch after 1 min of incubation. However, because starch reaching the large intestine may be more or less fermented by the intestinal microflora, RS is now defined herein as that fraction of dietary starch that avoids digestion in the small intestine. It is chemically measured as the difference between total starch (TS) obtained from a chemically treated, homogenized sample and the sum of RDS and SDS, generated from non-homogenized food samples by digestion with [the relevant reagents / methods]. MA / a / ZUZI / Ul 4DZ0 enzymes (RS = TS - (RDS + SDS)). Resistant starch is further classified normally as RS1, RS2, RS3 or RS4. RS1 refers to starch that is physically inaccessible because it is locked within the cell walls of plant matter and is therefore classified as resistant starch. RS1 resistant starch is found, for example, in partially milled grains, seeds, and legumes. RS1 is heat-stable under most normal cooking conditions and can be used as an ingredient in a wide variety of conventional foods. RS2 refers to native resistant starch, a component of starch granules such as those found in bananas (especially green bananas) and raw potatoes. Raw bananas and potatoes have relatively low gelatinization temperatures, typically in the range of approximately 60°C to 80°C, which often presents substantial problems in food formulation. Intragranular polymer rearrangements that lead to increased granular resistance to amylase digestion also fall into this category. This increased resistance could result from heat and / or moisture treatments or annealing of the intact granule. It is chemically measured as the difference between the glucose released by enzyme digestion of a boiled, homogenized food sample and that of a non-homogenized, unboiled food sample.In raw starch granules, starch is tightly packed in a radial pattern and is relatively dehydrated. This compact structure limits the accessibility of digestive enzymes, various amylases, and accounts for the resistant nature of RS2 as such, ungelatinized starch. In the diet, raw starch is consumed in foods such as bananas. RS1 and RS2 represent residues of starch forms that are digested very slowly and incompletely in the small intestine. 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 (corn flakes, for example), and starch pastes that have undergone extensive processing (through repeated cooking and cooling). It is chemically measured as the fraction that resists both dispersion by cooking and digestion with enzymes. It can only be dispersed with KOH or dimethyl sulfoxide. RS3 is completely resistant to digestion by pancreatic amylases. RS4 refers to specific starches that have been chemically modified and / or repolymerized (which may include molecular weight reduction), such as ethers, esters and cross-linked starches, as well as dextrins, pyrodextrins and maltodextrins altered with chain linkages. The resistant starch used in the present invention can be any resistant starch, such as any of the resistant starches RS1, RS2, RS3, or RS4, or any combination of two or more of the same. Preferably, the resistant starch used in the present invention is selected from RS2, RS3, and RS4, more preferably from RS2 and RS3. Most preferably, the resistant starch is RS2. According to the invention, resistant starch derived from sources such as corn, wheat, rice, legumes, peas, bananas, barley, triticale, sorghum, millet, cassava, oats, potatoes, tapioca, sago, ocarina, etc., can be used appropriately. In a preferred embodiment of the invention, the resistant starch is derived from corn, potatoes, or bananas, more preferably from corn or potatoes.In one embodiment of the invention, the resistant starch is selected from the group comprising resistant waxy corn starch; resistant regular or normal corn starch; resistant wheat starch; resistant rice starch; resistant legume, pea or pulse starch; resistant barley starch; resistant triticale starch; resistant sorghum starch; resistant millet starch; resistant cassava starch; resistant banana starch; resistant oat starch; resistant potato starch; resistant tapioca starch and resistant sago starch, more preferably from the group comprising resistant corn starch, resistant potato starch and resistant banana starch, most preferably from resistant corn starch and resistant potato starch. In embodiments of the invention, resistant starch is characterized by a specific amylose content. In one embodiment of the invention, resistant starch is characterized by a high amylose content, such as an amylose content, based on the total dry weight of the starch, of at least 35% by weight, for example, at least 40% by weight, at least 45% by weight, at least 50% by weight, or at least 55% by weight. There is no particular upper limit, although practically speaking, resistant starch will have an amylose content, based on the total dry weight of the starch, of less than 75% by weight, less than 70% by weight, less than 65% by weight, or less than 60% by weight. Currently, a high-amylose corn starch with an amylose content of up to 70% by weight is available. Based on X-ray diffraction patterns, starches can be classified as type A, type B, and type C. The type A structure has amylopectin with chain lengths of 23 to 29 glucose units. Hydrogen bonding between the hydroxyl groups of the amylopectin chains results in the formation of an outer double helix structure. Between these micelles, linear chains of amylose residues are packed, forming hydrogen bonds with the outer linear amylopectin chains. This pattern is very common in cereals. The type B structure consists of amylopectin with chain lengths of 30 to 44 glucose molecules with interdiffused water. This is the usual starch pattern in raw potatoes and bananas. The type C structure consists of amylopectin with chain lengths of 26 to 29 glucose molecules, a combination of type A and type B, which is typical of peas and beans. One of the reasons for enzyme resistance is the crystallinity of native type B starch granules. According to the present invention, it is preferred that the resistant starch be a type B (resistant) starch. In embodiments of the invention, the resistant starch is characterized by its specific granule size distribution. In one embodiment of the invention, the resistant starch is characterized by a volume-weighted average diameter D[4,3] of at least 5 µm, at least 7.5 µm, at least 10 µm, at least 12.5 µm, at least 15 µm, at least 17.5 µm, at least 20 µm, at least 22.5 µm, or at least 25 µm. In one embodiment of the invention, resistant starch is characterized by a volume-weighted mean diameter D[4,3] less than 150 pm, less than 100 pm, less than 75 pm, less than 50 pm, less than 40 pm, less than 35 pm, less than 30 pm or less than 25 pm.A volume-weighted mean diameter D[4,3] can be determined, for example, using a Malvern Mastersizer system. In embodiments of the invention, resistant starch is a high-amylose corn starch. Suitable, though not exhaustive, examples of high-amylose starch include HIMAIZE™ high-amylose starches (from Ingredion, Westchester, USA), such as HIMAIZE® 260. In embodiments of the invention, resistant starch is granular potato starch. A suitable example of this includes Type 2 resistant starch Potato Starch Food Grade Quality, which is derived from potatoes; it is a light beige, granulated powder, intended for use in food, and has a GRAS (Generally Recognized As Safe) status (from AVEBE, Veendam, The Netherlands). In embodiments of the invention, resistant starch is tapioca resistant starch. A suitable example of this includes C* Actistar 11700 (from Cerestar, France). The non-therapeutic methods and treatments described herein comprise the administration to the subject of 2'-FL with resistant starch, all as described herein, in an effective amount. Typically, the non-therapeutic methods involve the administration of the 2'-FL in unit-dose form. The resistant starch is also typically administered in unit-dose form. Such a unit dose may take any form, including the form of a food product comprising the 2'-FL and the resistant starch, wherein the food product is provided as a single portion, each portion comprising the 2'-FL and the resistant starch in a unit-dose amount. A single portion may be MA / a / ZUZI / U14DZ0 individually packaged. A unit dose is defined herein as the amount of an ingredient administered to a subject in a single dose. Depending on the unit dose, one or more individual portions may be administered during a day. The term "single portion" as used herein refers to a certain quantity and / or size of product that is suitable for consumption as a single serving by one individual. Such products may be in a ready-to-eat or ready-to-consume form or may be in a form that requires further processing, such as heating or the addition of heat or cold water. In one embodiment, the composition as used in the method of the invention is a food product, preferably in the form of a single serving, comprising 2'FL and resistant starch. A single serving may be individually packaged. In a preferred embodiment, the unit dose quantity of 2'-FL is at least 0.5 grams, at least 1 gram, at least 1.5 grams, at least 2 grams, at least 2.5 grams, at least 3 grams, at least 3.5 grams, or at least 4 grams. In another embodiment, the unit dose quantity of 2'-FL is at most 25 grams, for example at most 20 grams, at most 15 grams, at most 12.5 grams, at most 10 grams, at most 9 grams, at most 8 grams, at most 7 grams, at most 6 grams or even at most 5 grams. In yet another embodiment, the unit dose quantity of 2'-FL is in the range of 0.5 to 10 grams, preferably 1 to 8 grams, more preferably 2 to 4 grams. In one embodiment, the unit dose quantity of 2'-FL is 3 to 8 grams, preferably 3 to 7 grams, more preferably 3 to 6 grams. In yet another embodiment, the unit dose amount of resistant starch is at least 0.5 grams, for example at least 1 gram, at least 1.5 grams, at least 2 grams, at least 2.5 grams, at least 3 grams, at least 3.5 grams, or at least 4 grams. In one embodiment, the unit dose amount of resistant starch is at most 25 grams, for example at most 20 grams, at most 15 grams, at most 12.5 grams, at most 10 grams, at most 9 grams, at most 8 grams, at most 7 grams, at most 6 grams, or at most 5 grams. In one particular embodiment, the unit dose amount of resistant starch is from 0.5 to 10 grams. In yet another embodiment, the unit dose amount of 2'-FL is in the range of 0.5 to 15 grams and the unit dose amount of resistant starch is 0.5 to 15 grams; preferably the unit dose amount of 2'-FL is in the range of 1 to 10 grams and the unit dose amount of resistant starch is 1 to 10 grams; more preferably, the unit dose amount of 2'-FL is in the range of 2 to 8 grams and the unit dose amount of resistant starch is 1 to 8 grams. In another embodiment, the composition used in the method of the invention comprises at least 0.5 grams of 2'-fucosyl-lactose, for example at least 1.0 gram, such as at least 2.0, 4.0, 6.0, 8.0, 10.0, 12, or even at least 15 grams. In yet another embodiment, the composition further comprises at least 0.5 grams of resistant starch, for example at least 1.0 gram, such as at least 2.0, 4.0, 6.0, 8.0, 10.0, 12, or even at least 15 grams. As will be understood by those skilled in the art, based on the present teachings, administration according to the method of the invention is preferably by oral route, in the form of a single composition or, alternatively, 2'-FL and resistant starch are administered in two compositions that are administered simultaneously or sequentially. In embodiments in which the 2'-FL and the optional resistant starch are administered sequentially, it is preferred that the time between the administration of the respective compositions be at most 5 hours, preferably at most 4 hours, at most 3 hours, at most 2 hours, at most 1 hour, at most 30 minutes, at most 20 minutes, at most 15 minutes, at most 10 minutes, or at most 5 minutes. In the case of sequential administration, it is preferred that the resistant starch be administered before the administration of 2'-FL. The unit doses or compositions of 2'-FL and resistant starch are preferably administered at least once a week, preferably at least once every 3 days, at least once every two days, or at least once a day. In preferred embodiments of the invention, the non-therapeutic methods comprise the daily administration of unit doses of 2'-FL, or of 2'-FL and resistant starch, preferably once a day, twice a day, three times a day, or four times a day, more preferably once or twice a day, or most preferably once a day. According to the invention, the non-therapeutic methods as defined herein are preferably continued for a period of at least two weeks, more 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 one embodiment of the invention, the non-therapeutic methods comprise administering 2'-FL in an average amount of 0.5 to 32 grams per day, preferably in an average amount of 1 to 24 grams per day, more preferably in an average amount of 4 to 16 grams per day, for example approximately 12 grams per day, preferably for a period of at least 2 weeks, preferably at least 4 weeks, at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months or at least 6 months. In other embodiments, the non-therapeutic methods as defined herein comprise the administration of resistant starch in an average amount of 0.5 to 32 grams per day, preferably in an average amount of 2 to 24 grams per day, more preferably in an average amount of 3 to 16 grams per day, more preferably 4 to 12 grams per day, for example approximately 7.5 grams per day, preferably for a period of at least 2 weeks, preferably at least 3 weeks, at least 4 weeks, at least 1 month, at least 2 months, at least three months, at least 4 months, at least 5 months or at least 6 months. In further embodiments, 2'-FL is included in a composition. When 2'-FL is included in a composition, 2'-FL is preferably present in an amount of at least 5% by weight, at least 10% by weight, at least 20% by weight, at least 30% by weight, at least 40% by weight, at least 50% by weight, at least 60% by weight, at least 70% by weight, at least 80% by weight, at least 90% by weight, or at least 95% by weight compared to the total weight of the composition.In preferred embodiments, 2'-FL is present in a range from 5% by weight to 95% by weight, more preferably in a range from 10% by weight to 90% by weight, even more preferably in a range from 20% by weight to 80% by weight, more preferably still in a range from 25% by weight to 75% by weight, most preferably in a range from 30% by weight to 60% by weight compared to the total weight of the composition. In a particularly favorable embodiment, the composition comprises 2'-FL and resistant starch. In this embodiment, 2'-FL is present in the weight percent amounts as defined above, and the resistant starch is present in an amount of at least 5% by weight relative to the total weight of the composition. Preferably, 2'-FL is present in the composition in an amount of at least 5% by weight, and the resistant starch is present in an amount of at least 5% by weight relative to the total weight of the composition. More preferably, resistant starch is present in the composition in an amount of at least 10% by weight, at least 20% by weight, at least 30% by weight, at least 40% by weight, at least 50% by weight, at least 60% by weight, at least 70% by weight, at least 80% by weight, at least 90% by weight or at least 95% by weight compared to the total weight of the composition. In preferred embodiments, in the composition comprising 2'-FL and resistant starch, 2'-FL and resistant starch are provided in a weight ratio in the range of 0.5:10 to 10:0.5, preferably in a weight ratio in the range of 1:8 to 8:1, more preferably in the range of 2:6 to 6:2, and most preferably in the range of 3:5 to 5:3. In a preferred embodiment, 2'-FL and resistant starch are provided in the composition in a weight ratio of approximately 1:1. In yet another embodiment, the combined amount of 2'-FL and resistant starch in the composition as used in the non-therapeutic method of the invention is at most 30 grams, preferably at most 25 grams, more preferably at most 20 grams, and most preferably at most 15 grams. The maximum combined amount of 2'-FL and resistant starch as referred to in this embodiment refers to the maximum amount that an adult human subject may consume daily without disrupting normal defecation. Generally, higher amounts result in diarrhea or loose / watery stools. In another embodiment, the composition essentially consists of 2'-FL and resistant starch in amounts or in a ratio as defined above. In yet another embodiment of the non-therapeutic methods of the invention, 2'-FL is included in a food product preferably selected from the group comprising dairy products, for example, milk products, shakes, chocolate milk, yogurt, pudding, cream, cheese, ice cream, etc.; bars, such as nutrition bars, energy bars, snack bars, cereal bars, diabetic bars, etc.; liquid products, such as nutritional drinks, diet drinks, liquid meal replacements, sports drinks, and other fortified drinks; dessert products, such as pudding and yogurt; savory snacks, such as chips, tortillas, puffed and baked snacks, crackers, and pretzels; crackers; pastry products, such as muffins, cakes, and cookies; pasta, such as spaghetti; and food supplements, for example, tablets, capsules, or dry powder.Food supplements may be ready to consume or may need to be dissolved in a liquid such as water. The product in dry powder form may be accompanied by a device, such as a scoop, for measuring the desired amount of powder (e.g., daily or single dose). Food supplements may also include other ingredients commonly used in food supplements, such as vitamins, minerals, salts, etc. The food product is preferably selected from the group consisting of dairy products, liquid products, and food supplements. The composition as defined herein or the food product as defined herein may be provided in a jar, bottle, sachet, box, wrapper and the like. In preferred embodiments, the food composition or product as used in the method of the invention comprises 2'-FL and optionally resistant starch as defined herein, in an amount of at least 10% by weight, at least % by weight, at least 30% by weight, at least 40% by weight, at least 50% by weight, at least 60% by weight, at least 70% by weight, at least 80% by weight, at least 90% by weight or 100% by weight compared to the total weight of the food composition or product. In one embodiment, the food or dietary product is in the form of individual portions, each portion preferably comprising 0.5 to 25 grams of 2'-FL, more preferably 1 to 20 grams of 2'-FL; more preferably comprising 0.5 to 15 grams of 2'-FL and 0.5 to 10 grams of resistant starch, even more preferably comprising 0.5 to 10 grams, such as 2 to 8 grams, of 2'-FL, and 0.5 to 10 grams of resistant starch; particularly preferably comprising 0.5 to 10 grams, such as 2 to 8 grams, of 2'-FL, and 1 to 6 grams of resistant starch. Optionally, each individual portion may be individually packaged. The amount of 2'-FL or of the composition comprising 2'-FL and resistant starch as defined herein contained in a specific food product related to the invention depends on the type of food product, in particular its size and composition, as well as the frequency and quantity in which the product is to be consumed or is intended to be consumed. In a particularly preferred embodiment, several individual portions of the food product or dietary product to be used in the method of the invention can be packaged in a container to provide sufficient individual portions for several days, for example, a week or a month. In another aspect, the invention relates to 2'-fucosyl-lactose for use in the prevention of overweight or overweight-associated conditions in a subject, wherein the subject is a lean mammal, preferably a human, more preferably a human aged 2 years or older, with a body mass index (BMI) equal to or less than the maximum value indicated in Table 1 for the subject's age and sex. In one aspect, the invention relates to the use of 2'-fucosyl-lactose in the prevention of overweight or overweight-associated states in a subject, wherein the subject is a lean mammal, preferably a human, more preferably a human aged 2 years or older, with a body mass index (BMI) equal to or less than the maximum value indicated in Table 1 for the subject's age and sex. In yet another aspect, the invention relates to a composition comprising (i) 2'-fucosyl-lactose and (ii) resistant starch, for use in the prevention of overweight or overweight-associated conditions in a subject, wherein the subject is a lean mammal, preferably a human, more preferably a human aged 2 years or older, with a body mass index (BMI) equal to or less than the maximum value indicated in Table 1 for the subject's age and sex. In yet another aspect, the invention relates to the use of such a composition for maintaining a healthy body weight or losing body weight in a subject, wherein the subject is a lean mammal, preferably a human.In yet another aspect, the invention relates to the use of such a composition to increase the concentration of short-chain fatty acids (SCFAs), preferably acetate, in the distal colon of the subject, wherein the subject is a lean mammal, preferably a human. The therapeutic use of compositions comprising 2'-FL and resistant starch according to the invention will normally be based on the use of the same compounds, compositions, products, and quantities thereof, as well as the same routes of administration and the same dosage regimens as defined herein above in relation to non-therapeutic methods. As previously stated herein, the present invention lies in the finding that the (oral) administration of the combination of the invention to a subject results in an increase in SCFA levels in the distal colon. Without wishing to be bound by any theory, it is understood that such an increase in SCFA levels is beneficial for the prevention of a variety of diseases or conditions, including, in particular, overweight and overweight-related diseases and conditions. Because overweight is associated with the onset or progression of other diseases, the combinations and methods of the invention are also useful in methods for reducing complications associated with overweight, including vascular disease, hypertension, insulin resistance, diabetes, and musculoskeletal disorders. The present invention, in various embodiments, provides combinations for use in methods for preventing these diseases or conditions associated with overweight in a subject as defined herein. The invention also relates to a method for preventing overweight and / or a condition associated with overweight as defined herein, comprising MA / a / ZUZI / υΊ 4DZ0 said method the step of administering 2'-FL and RS to a subject as defined herein. In one embodiment, in the method for preventing overweight and / or a state associated with overweight, 2'-FL is comprised in a composition that further comprises resistant starch. In the method for preventing overweight and / or a state associated with overweight according to the invention, 2'-FL and resistant starch are used in the same amounts, ratios, dosage regimens, dietary products, etc., as defined herein. In yet another aspect, the invention relates to the use of 2'-FL and RS in the manufacture of a medicament for the treatment of overweight or conditions associated with overweight. In yet another aspect, the invention relates to a composition comprising at least 5% by weight of 2'-FL and at least 5% by weight of resistant starch, wherein the weight percent is determined based on the total solids of the composition. Preferably, the total amount of insoluble, non-digestible carbohydrates in this aspect of the invention is between 10 and 100% up to 95% by weight based on total solids. More preferably, the total amount of 2'-FL and resistant starch in this aspect of the invention is between 25 and 75% by weight based on total solids. The composition of the invention, or the composition as used in the use or method of the invention, may further comprise other ingredients that may contribute to the subject's general well-being. In one embodiment, these other ingredients include probiotics, in particular probiotics that may help a subject lose weight, such as Lactobacillus fermentum, Lactobacillus amylovorus, or Lactobacillus gasseri. In another embodiment, other ingredients of this type may comprise one or more ingredients selected from the inulin group, oligofructans (i.e., fructo-oligosaccharides (FOS)), xylans (i.e., xylo-oligosaccharides (XOS)), mannans (i.e., mannan-oligosaccharides (MOS)), beta-glucans (i.e., beta 1-3, beta 1-4 and / or 1-6 beta-glucans), pectins, vitamins, and galacto-oligosaccharides (GOS). Preferably, such other ingredients comprise one or more ingredients from the inulin group and oligofructans (i.e., fructo-oligosaccharides (FOS)). Another aspect of the invention relates to a method of treating a human suffering from unwanted weight gain by administering an effective amount of 2'-FL, preferably by administering an effective amount of 2'-FL and resistant starch. The amount of 2'-FL and resistant starch per day, dosage, unit, or portion is as defined elsewhere herein. In one embodiment of this aspect, the subject is of lean body weight, preferably 18 years of age or older. Another aspect of the invention relates to a method of treating a human who wishes to lose body weight or maintain a healthy body weight by administering an effective amount of 2'-FL, preferably by administering an effective amount of 2'-FL and resistant starch. The amount of 2'-FL and resistant starch is as defined elsewhere herein. In one embodiment of this aspect, the subject is of lean body weight, preferably 18 years of age or older. Except as otherwise expressly stated, all numerical quantities in this description indicating amounts of material or conditions of reaction and / or use are to be understood as modified by the word "approximately" in the description of the broader scope of the invention. It is generally preferred to practice the invention within the numerical limits stated. Also, unless expressly stated otherwise: percentage, parts of, and ratio values are by weight; the description of a group or class of materials as suitable or preferred for a given purpose in relation to the invention implies that mixtures of any two or more of the members of the group or class are equally suitable or preferred;The description of constituents in chemical terms refers to the constituents at the time of addition to any composition specified in the description and does not necessarily exclude chemical interactions between the constituents of a mixture once mixed; the first definition of an acronym or other abbreviation is applicable to all subsequent uses herein of the same abbreviation and applies, mutatis mutandis, to normal grammatical variations of the abbreviation initially defined; and, unless expressly stated otherwise, the measurement of a property is determined by the same technique as referenced before or after for the same property. It should also be understood that this invention is not limited to the specific embodiments and methods described herein, as the specific components and / or conditions may, of course, vary. Furthermore, the terminology used herein is solely for the purpose of describing particular embodiments of the present invention and is not intended to be limiting in any way. It should also be noted that, as used in the descriptive memorandum and accompanying claims, the singular form "a," "one," "an," "the" includes plural referents unless the context clearly indicates otherwise. For example, a reference to a component in the singular is intended to include a plurality of components. In this description, any reference to weight, weight ratio and the like shall be understood to refer to dry matter, in particular to the dry matter of the composition. Unless otherwise defined, all technical and scientific terms used herein generally have the same meaning as commonly understood by a person skilled in the art to which this invention pertains. As used herein, the term comprising, which is synonymous with including or containing, is open-ended and does not exclude additional unstated element(s), ingredient(s), or method step(s), whereas the term consisting of is a closed term that excludes any additional element, step, or ingredient not explicitly stated. As used herein, the term consisting essentially of is a partially open term, which does not exclude additional unmentioned element(s), stage(s) or ingredient(s), as long as such additional element(s), stage(s) or ingredient(s) do not materially affect the basic and novel properties of the invention. As used herein, the term "comprising" therefore includes the term "consisting of" as well as the term "essentially consisting of". Accordingly, the term "comprising" is understood, in this application, to more particularly encompass the term "consisting of" and the term "essentially consisting of". Throughout this application, where reference is made to publications, the descriptions of these publications are incorporated herein in their entirety by reference in this application to more fully describe the prior art to which this invention belongs. The invention is illustrated below in this document with reference to the following non-limiting example. EXAMPLE In vitro fermentation model, TIM-2 In vitro fermentation studies were performed using the TIM-2 model. This is a validated, dynamic, computer-controlled model that simulates the human colon, mimicking body temperature, lumen pH, absorption of water and microbial metabolites through a semipermeable membrane within the model, mixing and transporting intestinal contents with peristaltic movements, using an anaerobic microbiota of human origin. This basically corresponds to the model as described in Minekus, M„ et al. Appl. Microbiol. Biotechnol. 1999 53, 108-114. doi: 10.1007 / S002530051622 and Kortman et al., Frontiers in Microbiology 2016, 6, 1481. The characteristics of the movements of the contents in the TIM-2 system are simulated using an increase in pH and peristaltic movements of the contents in the system using peristaltic pumps as described in Minekus, M (1998. Development and validation of a dynamic model of the gastrointestinal tract. Doctoral thesis, Delft University of Technology, Netherlands). AGCC Analysis The analysis of AGCC was performed at Brightlabs BV (Venlo, Netherlands, according to (Sayago-Ayerdi SG, et al. Food Research International, E-pub date December 13, 2017; Sayago Ayerdi et al Food Research International 118 (2019) 89-95). Inoculum Pooled fecal microbiota samples from 11 healthy lean subjects who did not suffer from any metabolic disease were used to inoculate the TIM-2 in vitro fermentation model. Vitamin blend A mixture of vitamins was used that contained (per liter): 1 mg of menadione, 2 mg of D-biotin, 0.5 mg of vitamin B12, 10 mg of pantothenate, 5 mg of nicotinamide, 5 mg of p-aminobenzoic acid and 4 mg of thiamine. Dialysis The dialysate used in the TIM-2 system contained (per liter): 2.5 g of K2HPO4-3H2O, 4.5 g of NaCl, 0.005 g of FeSO4-7H2O, 0.5 g of MgSO4-7H2O, 0.45 g of CaCl2-2H2O, 0.05 g of bile and 0.4 g of cysteine HCl, plus 1 ml of the vitamin mixture. Example 1 The fecal microbiota was freshly sampled and stored directly (within a 2 h interval) on ice under anaerobic conditions. Subsequently, in an anaerobic chamber, the samples were diluted 1:1 with dialysate and combined in approximately equal weights, after which glycerol was added (to a final concentration of 12-13 w / w) and aliquots (30 ml / tube) were frozen in liquid nitrogen and stored at -80 °C. Prior to inoculation, four 30 mL aliquots were taken from the freezer at -80°C and thawed in a water bath at 37°C for exactly 1 hour (still under anaerobic conditions). In an anaerobic chamber, the microbiota from the four tubes was combined, and the same volume of previously reduced (i.e., oxygen-free) dialysate was added. The mixture was gently blended and divided into four syringes, each containing approximately 60 mL of microbiota-containing fluid. The syringes were sealed with a small flexible tube secured with a tube clamp. Each TIM-2 unit was inoculated with one of the four syringes (i.e., 60 mL of microbiota / dialysate mixture) using a single-unit sample port. After introducing the microbiota into the unit, another ml of previously reduced dialysate was added to the TIM-2 unit to reach a final volume of 120 ml per unit (i.e., system). To simulate conditions in the proximal colon, the transverse colon, and the distal colon, the pH of the microbiota / dialysate mixture was increased from pH 5.8 to pH 7.0 using 1 M NaOH over a 24-hour period. The pH increase simulated fiber trafficking through the colon during the 24-hour experiment (in which the last 16 hours simulated the most distal colonic site (i.e., transverse + distal)). Samples (1 ml) were taken for SCFA analysis after 1, 2, 4, 6, 8 and 24 h after insertion of test product; cumulative absolute amounts of SCFA were determined. Samples were centrifuged at 14,000 rpm for 10 min, filtered through a 0.45 µm PTFE filter, and diluted in the mobile phase (1.5 mM aqueous sulfuric acid). Ten microliters were loaded onto the column using a 730 autosampler (Metrohm, Herisa, Switzerland). Acids were eluted according to their pKa. Analysis was performed by ion-exclusion chromatography (IEC) using an 883 chromatograph (IC, Metrohm) equipped with a Transgenomic IC Sep ICE-ION-300 column (30 cm × 7.8 mm × 7 µm) and a MetroSep RP2 Guard. A column flow rate of 0.4 mL / min was used at a column temperature of 65 °C. Acids were detected using suppressed conductivity detection. Analyses were performed by Brightlabs (Venlo, The Netherlands). Addition of the test product: After an adaptation period of 40 h, 7.5 grams of 2'-fucosyl-lactose (2'-FL) or 7.5 grams of 2'-FL and 7.5 grams of resistant starch (RS2 tapioca starch, Avebe, Veendam, Netherlands) were introduced into a TIM-2 unit through the sample port (Wednesday) as a single shot. An experimental week contained the following stages: Monday: Start up the 4 units of the TIM-2 system (pH 5.8). Tuesday: Feed the simulated efflux medium (SIEM) (Maathuis et al 2009 Journal of the American College of Nutrition 28(6):657-66 DOI: 10.1080 / 07315724.2009.10719798); The simulated efflux medium (SIEM) contained 5.7 g / liter of BD Bacto tryptone (BD), 2.4 g / liter of D-glucose (Sigma-Aldrich), 6.14 g / liter of NaCl (Roth, Germany), 0.68 g / liter of KH2PO4 (Merck, Germany), 0.3 g / liter of NaH2PO4 (Merck, Germany), 1.01 g / liter of NaHCO3 (Merck, Germany), 5.6 g / liter of bile salts n.s3 (Difeo), 0.2 g / liter of lysozyme (Serva, Germany), 1,000 U of α-amylase (Fluka, Germany), 110 U of trypsin (Sigma-Aldrich), 380 U of chymotrypsin (Calbiochem, Germany) and 960 U of lipase (Sigma-Aldrich). D(+)-Glucose and enzymes were sterilized by filtration before addition. Wednesday: Starvation period for 3 h followed by a single insertion of the test product; [2'-FL (7.5 grams of 2'-FL or 7.5 grams of 2'-FL + 7.5 grams of resistant starch) were added through the sample port]; after the introduction of the test product, samples were taken for SCFA analysis after 1, 2, 4, 6 and 8 h. Thursday: 24 h after insertion of the test product: the last sample was taken for AGCC analysis; Friday: clean, (the experiment was run over one week). Results The increase in acetate concentration between the last two sampling points (i.e., between 8 and 24 hours after sample insertion) was taken as an indication of increased SCFA and acetate in the distal colon. The results of the experiments are represented below in Table 2. Table 2. Results of TIM-2 experiments using microbiota samples from lean subjects who were administered either 2'-FL alone or a combination of 2'-FL and resistant starch (RS). MA / a / ZUZI / υΊ 4DZ0 Test product Thin (18.5 kg / m2 < BMI < 25 kg / m2) Acetate AGCC 2'-FL without RS 12 mmol 21 mmol 2'-FL with RS 20.5 mmol 30 mmol In Table 2, the amounts of acetate and short-chain fatty acids (SCFAs) refer to the amounts produced between 8 and 24 hours after insertion of the test product; representing the amounts of acetate and SCFAs produced in the distal colon. The experiment shows that in lean subjects (with a BMI ranging from at least 18.5 kg / m2 to less than 25 kg / m2), SCFA levels, and particularly acetate levels, increased in the distal colon when 2'-FL was added. When both 2'-FL and resistant starch were added, the amounts of SCFAs, and particularly acetate, were even higher.
Claims
1. A non-therapeutic method for maintaining a healthy body weight or losing body weight in a subject, characterized in that the non-therapeutic method comprises the step of administering 2'-fucosyl-lactose (2'-FL) and resistant starch to the subject; wherein the subject is a lean mammal, preferably a human; wherein the method does not comprise the step of administering breast milk to the subject.
2. A non-therapeutic method for increasing the concentration of short-chain fatty acids (SCFAs), preferably acetate, in the distal colon of a subject, for the prevention of diet-induced body weight gain or adiposity; or for the improvement of glucose homeostasis and / or insulin sensitivity; wherein the non-therapeutic method comprises the step of administering 2'-fucosyl-lactose (2'-FL) to the subject, wherein said subject is as defined in claim 1 and wherein the method does not comprise the step of administering breast milk to the subject.
3. Non-therapeutic method according to claim 1, wherein the concentration of SCFAs, preferably acetate, is increased in the distal colon of the subject.
4. A non-therapeutic method according to any of the preceding claims, wherein the subject is a human aged 2 years or older, with a body mass index (BMI) equal to or less than the upper value indicated in Table 1 for a healthy body weight for the subject's age and sex. Table 1 Definition of BMI values for healthy body weight Age Male BMI (healthy body weight) Female BMI (healthy body weight) 2 15.14-18.40 14.83-18.01 3 14.74-17.88 14.47-17.55 4 14.43-17.54 14.19-17.27 5 14.21-17.41 13.94-17.14 6 14.07-17.54 13.82-17.33 7 14.04-17.91 13.86-17.74 8 14.15-18.43 14.02-18.34 9 14.44-19.09 14.28-19.06 10 14.64-19.83 14.61-19.85 Age Male BMI (healthy body weight) Female BMI (healthy body weight) 11 14.97-20.54 15.05-20.73 12 15.35-21.21 15.62-21.67 13 15.84-21.90 16.26-22.57 14 16.41-22.61 16.88-23.33 15 16.98-23.28 17.45-23.93 16 17.54-23.89 17.91 -24.36 17 18.05-24.45 18.25-24.69 >18 18.50-24.99 18.50-24.99 5. Non-therapeutic method according to any one of the preceding claims, wherein the administration is oral.
6. A non-therapeutic method according to any one of the preceding claims, wherein LNnT is not administered to the subject.
7. Non-therapeutic method according to any one of the preceding claims, wherein the 2'-fucosyl-lactose is comprised in a composition that optionally comprises resistant starch.
8. Non-therapeutic method according to claim 7, wherein the composition comprises an amount of 2'-fucosyl-lactose of at least 0.5 g and optionally comprises an amount of resistant starch of at least 0.5 g.
9. A non-therapeutic method according to any one of claims 6 to 8, wherein the weight ratio of 2'-fucosyl-lactose to resistant starch is in the range from 0.5:10 to 10:0.
5.
10. Non-therapeutic method according to any one of claims 6 to 9, wherein the combined amount of 2'-FL and resistant starch is at most 30 grams, preferably at most 25 grams, more preferably at most 20 grams, most preferably at most 15 grams.
11. A non-therapeutic method according to any one of claims 6 to 10, wherein the composition is a food product, preferably wherein the food product is selected from the group consisting of dairy product, bar, liquid product, dessert-type product, savory snack, cracker, pastry product, pasta, and food supplement.
12. A non-therapeutic method according to any one of claims 6 to 11, wherein the composition is in the form of individual portions; or according to any one of claims 9 or 10, wherein the food product is in the form of an individual portion; optionally, such individual portion is individually packaged.
13. Composition comprising (i) 2'-fucosyl-lactose and (ii) resistant starch; for use in the prevention of overweight or an overweight-associated state in a subject, wherein the subject is as defined in claim 1.
14. Use of a composition comprising 2'-fucosyl-lactose and resistant starch for maintaining a healthy body weight or losing body weight in a subject, wherein said subject is as defined in claim 1.
15. A composition comprising at least 5% by weight of 2'-FL and at least 5% by weight of resistant starch as determined on a dry matter basis.