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    • 专利摘要:
    The present invention relates to a composition for supporting and / or improving intestinal health in athletes comprising an effective dose of at least one human milk oligosaccharide (HMO) from the group of 2'-fucosyllactose (2'-FL), 3-fucosyllactose ( 3-FL), lactodifucotetraose (DF-L), lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), lacto-N-fucopentaose I (LNFP I), lacto-N-difucohexaose II (LNDFH II ), lacto-N-neodifucohexaose II (LNnDFH II), para-lacto-N-neohexaose (para-LNnH), lacto-N-neooctaose (LNnO), lacto-N-fucopentaose V (LNFP V), lacto-N- neofucopentaose V (LNnFP V), 3'-sialyl-3-fusoyllactose (F-SL), LS-tetrasaccharide a (LSTa), 3'-sialyllactose (3'-SL), or combinations thereof.
    公开号:BE1027078B1
    申请号:E20195134
    申请日:2019-03-05
    公开日:2020-09-21
    发明作者:Riet Nikolaas Van
    申请人:Nutribam Bvba；
    IPC主号:
    专利说明:

    COMPOSITION, NUTRITIONAL SUPPLEMENT AND PROCEDURE FOR SUPPORTING AND / OR IMPROVING GUT HEALTH
    TECHNICAL DOMAIN The invention relates to gut health. More specifically, the invention is in the technical field of compositions for supporting and / or improving gut health.
    STATE OF THE ART The regular practice of exercise and / or sport offers many benefits, including protection against the development of chronic diseases and improving quality of life. These benefits are attributed to, among other things, the anti-inflammatory effects and the enhancement of neuromuscular function associated with exercise. In addition, intensive sports practice leads to changes in the gut microbiota, which is closely related to the athlete's well-being. Thus, the gut microbiota plays an important role in the production, storage and consumption of energy obtained from the diet, as well as in inflammation, redox reactions and the hydration status. However, the correlation between physical activity and the gut microbiota can also be disadvantageous for athletes, especially elite athletes. Long and intensive training, for example, may lead to disruptions in the gut microbiota. As a result, the athlete delivers significantly less sports performance and his recovery capacity is drastically reduced. A disrupted gut microbiota also reduces the functioning of the immune system, which puts athletes at greater risk of disease, infections, especially intestinal disorders. Athletes who regularly consume nutritional supplements, and in particular supplements rich in fructose and / or artificial sweeteners, also run an increased risk of disrupted gut microbiota and infection as these components reach the intestinal system intact and can function as potential nutrients for pathogenic bacteria.
    There is therefore a need to support and / or improve gut health in athletes in order to support the immune system, minimize the risk of infections, and optimize athletes' athletic performance and recovery capacity. WO 2017 180 501 describes a probiotic composition for improving sports performance and recovery. However, the prebiotic composition according to WO 501 has only a limited influence on the athlete's immune system and the risk of infections related to the occurrence of pathogenic bacteria in the gastrointestinal tract is little or not affected.
    WO 2018 187 792 describes a 2'-fucosyllactose component and a method for using said component to treat inflammatory bowel disease, such as Crohn's disease and ulcerative colitis, or to reduce the risk of relapse in inflammatory bowel disease. WO * 792, however, emphasizes inflammatory bowel disease. No indication is given as to how 2'-fucsyllactose can be used non-therapeutically to improve and / or support intestinal health in athletes who undertake long-term and intensive sports performances.
    The present invention aims to solve at least some of the above-mentioned problems or drawbacks.
    SUMMARY OF THE INVENTION To this end, the invention provides a composition for supporting and / or improving gut health in athletes according to claim 1. The composition comprises an effective dose of at least one human milk oligosaccharide (HMO) selected from the group of 2 ' '-fucosyllactose (2 /' -FL), 3-fucosyllactose (3-FL), lactodifucotetraose (DF-L), lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), lacto-N-fucopentaose I (LNFP I), lacto-N-difucohexaose II (LNDFH II), lacto-N-neodifucohexaose II (LNnDFH II), para-lacto-N-neohexaose (para-LNnH), lacto-N-neooctaose (LNnO), lacto-N-fucopentaose V (LNFP V), lacto-N-neofucopentaose V (LNnFP V), 3 "-sialyl-3-fusoyllactose (F-SL), LS-tetrasaccharide a (LSTa), 3" -sialyllactose (3 '-SL), or combinations thereof.
    The composition according to the present invention is an optimally suitable supplement to a sports diet and allows full training without impacting intestinal health. This also optimizes recovery and minimizes the risk of infections. Preferred forms of the composition are given in dependent claims 2 to 13. A second aspect concerns a method for guiding a subject, and / or improving the sports performance and / or recovery of a subject, according to claim 14. The method comprises determining whether a subject is a secretor or non-secretor of an HMO; and administering an effective dose of an HMO to the subject. Preferred forms of the method are given in sub-claims 15 to 15
    22.
    DETAILED DESCRIPTION The present invention relates in a first aspect to a composition for supporting and / or improving gut health in athletes.
    Unless defined otherwise, all terms used in the description of the invention, including technical and scientific terms, have the meaning as commonly understood by those skilled in the art of the invention. For a better assessment of the description of the invention, the following terms are explicitly explained. "A", "the" and "it" in this document refer to both the singular and plural unless the context clearly suggests otherwise. For example, “a segment” means one or more than one segment.
    When “about” or “around” is used in this document for a measurable quantity, parameter, time or moment, and the like, it means variations of +/- 20% or less, preferably +/- 10% or less, more preferably +/- 5% or less, even more preferably +/- 1% or less, and even more preferably +/- 0.1% or less than and of the quoted value, to the extent that such variations of are applicable in the described invention. However, this should be understood to mean that the value of the quantity using the term “approximately” or “round” is itself specifically disclosed. The terms “comprise”, “comprising”, “consist of”, “consisting of”, “incorporating”, “containing”, “containing”, “containing”, “containing” are synonyms and are inclusive or open terms that define the indicate the presence of what follows, and which do not exclude or prevent the presence of other components, features, elements, members, steps known from or described in the prior art.
    Quoting numeric intervals through the endpoints includes all integers, fractions, and / or real numbers between the endpoints, including these endpoints. A first aspect of the present invention relates to a composition for supporting and / or improving gut health in athletes, the composition comprising an effective dose of at least one human milk oligosaccharide (HMO) selected from the group of 2 "-fucosyllactose (2 "-FL), 3-fucosyllactose (3-FL), lactodifucotetraose (DF-L), lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), lacto-N-fucopentaose I (LNFP I), lacto-N-difucohexaose II (LNDFH II), lacto-N-neodifucohexaose II (LNnDFH II), para-lacto-N-neohexaose (para-LNnH), lacto-N-neooctaose (LNnO), lacto-N-fucopentaose V (LNFP V), lacto-N-neofucopentaose V (LNnFP V), 3'-sialyl-3-fusoyllactose (F-SL), LS-tetrasaccharide a (LSTa), 3 ”sialyllactose (3'-SL), or combinations of it. The term "human milk oligosaccharides" (HMO) in light of the present invention refers to sugar molecules naturally occurring in human breast milk. HMOs have a prebiotic effect in the newborn and are essential for the development of healthy intestinal flora. HMOs in light of the present invention are available from both a natural and synthetic source. An "effective dose" in the context of the present invention refers to an "effective dose" and can be interpreted as the minimum dose at which the beneficial effects of the administered composition are reflected. The term “gut health” refers to the gut microbiota, also microbiome, or the microorganisms present in the digestive tract. The gut microbiota of an individual can include up to 30,000 different types of bacteria, some of which perform important or even necessary functions, while others are rather detrimental to the well-being of the subject in which they are present. Good gut health implies a healthy balance between the various microorganisms in the digestive system and promotes the general health of the subject.
    5 The term “athlete” can be interpreted as any individual who engages in sports activities. Sports activities according to the present invention include, but are not limited to, swimming, soccer, karate, hockey, strength training, weight lifting, shot put, gymnastics, track and field, cycling, running, sprinting, hurdling, skating, rowing, long jump. , boxing, skiing, anaerobic training, aerobics, or combinations thereof.
    The present invention, and more specifically the presence of an effective dose of at least one human milk oligosaccharide, has the advantage of effectively supporting bowel function in a subject, preferably an athlete. The target group of the present invention is particularly susceptible to gastrointestinal disturbances, as athletes regularly put their bodies to extreme strain. Since a large amount of catecholamines are released during intensive sports performances, this can make a significant contribution to disturbed intestinal health. For example, catecholamines can dramatically increase the growth of Gram-negative bacteria such as Escherichia coli and Yersinia enterocolitica. The ability of enteric bacteria to respond directly to stress-related neuromediators such as catecholamines acts at the level of the intestinal mucosa, which represents a complex network of epithelial cells, immunocytes and nerves in direct contact with the external environment. The composition of the present invention supports and / or improves gut health thereby reducing the negative influence of catecholamines. The composition according to the present invention is an optimally suitable supplement to a sports diet and allows the athlete to train fully without impacting gut health. Moreover, the athlete is better and faster able to recover after intensive training.
    The term “pathogenicity” denotes the potential pathogenic potential of an organism or substance. Typically the term "pathogen" is used to describe an infectious microorganism or agent, such as a virus, bacteria, protozoa, or fungus.
    "Catecholamines" are neurotransmitters produced by the adrenal glands and the postganglionic fibers of the sympathetic nervous system. They include dopamine, epinephrine (adrenaline) and norepinephrine. Each of these neutrotransmitters is broken down into breakdown products which are excreted in the urine.
    Catecholamines are usually released into the bloodstream as a result of physical or emotional stress, where dopamine and norepinephrine in particular also exert a hormonal effect. They are produced in significant quantities to provide intensive sports performance and have an indirect, negative impact on intestinal health.
    "Epithelial tissue" or "epithelium" is the tissue that lines the outer surfaces of organs and blood vessels in the body, as well as the inner surfaces of internal organs. Epithelial tissue forms a large surface that is in direct contact with the microbial flora present in the intestinal tract.
    Preferably, the human milk comprises oligosaccharide (HMO) 2'-fucosyllactose (2'-FL).
    The effective action of 2'-FL is based on its resemblance to certain pathogenic receptors found on the gut wall. As a result, 2 ”-FL acts as an analog for these pathogenic receptors in several cases, significantly reducing the risk of infections. HMOs, and in particular 2'-FL, have a direct effect on the gut epithelial structure and interfere with the adhesion of various pathogenic bacteria, toxins, parasites and viruses. In one embodiment, the HMOs interfere with bacteria from the group of Campylobacter jejuni, Escherichia coli, Vibrio cholerae, Salmonella fyris, Helicobacter pylori, or combinations thereof.
    In a further or different embodiment, the human milk oligosaccharide (HMO) comprises 2 ”-fucosyllactose (2” -FL) and / or derivatives thereof, which derivatives retain at least 70% of the biological functions of native 2'-FL. Preferably at least 80% of the biological functions are retained, more preferably at least 90%, most preferably at least 99%. Said biological functions of 2'-FL include its beneficial effects on the intestinal function such as - anti-inflammatory effects, antibacterial adhesion effects, prebiotic effects etc.
    The human milk oligosaccharides (HMOs) described herein can be prepared by any technique known in the art. In one embodiment, the HMOs can be synthetically produced. Synthetic production of HMOs is possible, among other things, via microbial fermentation, enzymatic processes, chemical synthesis, or combinations thereof. In some embodiments, the HMOs are synthesized by recombinant microorganisms such as Escherichia coli and / or Corynebacterium glutamicum.
    In a further or different embodiment, the effective dose of the human milk oligosaccharide (HMO) is comprised between 0.5 and 5.0 g / day. Within this range, the present composition is effective as a curative and / or preventive agent for reduced intestinal motility and painful intestines. Athletes produce an increased dose of norepinephrine to deliver long-lasting and intensive sports performance, which has the function of mobilizing the brain and body for action. One of the effects of norepinephrine is to reduce blood flow to the gastrointestinal system and to inhibit bladder and gastrointestinal motility. This inhibition of motility by norepinephrine may contribute to reduced gut health. The composition according to the present invention provides a solution for this, as it optimally stimulates and / or supports intestinal motility.
    Preferably, the effective dose of the human milk oligosaccharide (HMO) is comprised between 1.8 and 2.2 g / day. The dose is particularly suitable when using sports supplements comprising a high content of fructose and / or artificial sweeteners. The frequent use of fructose in sports drinks and supplements has been associated with reduced gut health. Fructose reaches both the liver and the gut microbiota, fueling pathogenic bacteria and potentially overgrowing beneficial bacteria. Consequently, the risk of infections is higher. The present composition decreases pathogenicity as the binding of pathogens to receptors on epithelial cells in the intestinal tract is decreased. Pathogens or toxins bind to the HMOs and are eventually cleared from the gastrointestinal tract. This significantly reduces the risk of (pathogenic) infections.
    A specific advantage of the composition according to any of the preceding embodiments is the inhibition of lipopolysaccharide (LPS) induced inflammation. Gram negative pathogenic bacteria are able to activate mucosal inflammation by binding the lipopolysaccharide matrix (LPS) to receptors present on the gut wall. The composition of the present invention is able to attenuate said LPS-induced inflammation by modulating the expression of the CD14 gene. The CD14 gene encodes a protein that is crucial for the proper functioning of the immune system and counteracts LPS-induced inflammation.
    Thus, the composition of the present invention contributes to the general well-being of the athlete, as the risk of bacterial infections is reduced, LPS-induced inflammation is inhibited and gut motility is stimulated.
    The increased well-being of the athlete directly leads to significantly improved sports performance and a reduced recovery time. "Lipopolysaccharides", also "lipoglicans", are polymeric molecules comprising a lipid portion, a polysaccharide portion and the so-called "O-antigen". They occur as the outer membrane of Gram-negative bacteria, which interact with receptors on the gut wall.
    In accordance with a further or different embodiment of the composition, the athletes have taken a course of antibiotics prior to administration of the composition.
    Following a course of antibiotics is detrimental to the athlete's intestinal health.
    After following the course, the athlete is therefore more susceptible to new infections, which significantly undermine the athlete's performance and recovery.
    Prior to administration of the composition, it is determined in one embodiment whether the athletes are secretor or non-secretor of said HMO.
    Non-secretors are naturally incapable of producing the aforementioned HMO, and are therefore particularly susceptible to gut health problems and the associated risks, as described in previous embodiments.
    In one embodiment, the athletes are tested for the presence or absence of one or more genetic polymorphisms or mutations prior to administration of the composition.
    Such polymorphisms or mutations in the genetic material can be indicators of reduced or absent production of HMOs and thus can be indicators of an increased risk of decreased gut health, pathogenic infections, decreased gut motility or even chronic bowel disease.
    Preferably, said polymorphisms or mutations concern the FUT 2 gene.
    The FUT 2 gene is involved in the production of 2'-FL, whereby individuals with an inactivating polymorphism in the FUT2 gene are termed non-secretors.
    Non-secretors are deficient in innate gut carbohydrates containing fucose, which makes it more prone to gut dysbiosis. The term “intestinal dysbiosis” refers herein to an imbalance between different microorganisms present in the intestinal system. In addition, non-secretors have a higher risk of intestinal disorders such as Crohn's disease.
    The polymorphisms mentioned relate in particular to the single nucleotide polymorphisms (SNPs) rs601338, rs492602, rs516246 and / or rs602662. SNPs according to this numbering can be found on databases such as SNPedia. In one embodiment, the composition further comprises one or more excipients, wherein the HMO and the excipients are in a ratio comprised between 1: 8 and 6: 8. The composition can also be interpreted in this light as a dietary supplement or sports supplement. A ratio between 1: 8 and 6: 8 allows the HMO, and in particular the 2 ”-FL, to be optimally active towards one or more of its effects, the one or more excipients providing the composition of additional, beneficial effects. Moreover, within the present ratios, the composition poses little or no additional burden on the gastrointestinal tract and is optimally absorbed by the subject. Preferably, the 2'-fucosyllactose and the one or more excipients are in a ratio between 1: 8 and 3: 8. The present ratios allow more adjuvants to be added to the composition, thereby obtaining multiple additional effects.
    In one embodiment, the one or more excipients are selected from the group of amino acids, monosaccharides, micronutrients, antioxidants, vitamins, vegetable extracts, fibers, derivatives of any of the foregoing excipients, or combinations thereof.
    The vitamins are, according to one embodiment, selected from the group of vitamin A, vitamin D, vitamin E, vitamin K, thiamine, riboflavin, pyridoxine, vitamin C, carotenoids, niacin, folic acid, pantothenic acid, biotin, choline, inositol, their salts and derivatives. , and combinations thereof. The adjuvants of the present invention contribute to the proper functioning of the gastrointestinal tract, support intestinal health and support the general well-being of the subject, in particular the athlete.
    The present invention includes according to one embodiment vegetable extracts selected from the group of ginger extract, soy extract, garlic extract, echinacea extract, ginseng extract, St. John's wort extract, elderberry extract,
    cranberry extract, turmeric extract, Ginkgo biloba extract, or combinations thereof.
    They are a natural source of polyphenols and may act as an antioxidant and / or support the immune system and athletic performance.
    Preferably, the composition comprises cranberry extract.
    The use of cranberry extract in the present composition is particularly advantageous, as cranberry extract acts as proanthocyanidin and is able to trigger beneficial bacterial strains such as Akkermansia muciniphila.
    In some embodiments, the composition includes one or more polyphenols, preferably proanthocyanidins, to stimulate the growth of Akkermansia muciniphila in the intestinal microbiome.
    This addition influences, in particular through the aforementioned proliferation of Akkermansia, various metabolic processes, with a favorable effect on the body composition.
    In particular, Akkermansia proliferation has been associated with the maintenance of a low fat percentage.
    Taking into account the sporting target group of the present invention, this is an important additional advantage of the composition.
    In the light of the present invention, the amino acids preferably include glutamine, and branched chain amino acids (BCAA), namely leucine, isoleucine and / or valine.
    During intensive training they can be used directly as a source of energy.
    In addition, they contribute, particularly leucine, in activating muscle protein synthesis.
    In combination with the HMOs of the present invention, the recovery time is further shortened. "Antioxidants" are components that are able to trap free radicals and thus reduce oxidative stress.
    In one embodiment, the composition comprises one or more antioxidants suitable for oral administration, including vitamin A, vitamin E, vitamin C, retinol, tocopherol, carotenoids including lutein, beta-carotene, zeaxanthin, lycopene, and combinations thereof.
    Said micronutrients, in one embodiment, include calcium, phosphorus, sodium, chloride, magnesium, manganese, iron, copper, zinc, selenium, iodine, chromium, molybdenum, or combinations thereof.
    The composition, or also the nutritional supplement or the sports supplement, according to the present invention further comprises according to one embodiment one or more proteins, carbohydrates and / or fats.
    The food supplement can be used as a supplement to a healthy diet and can support the athlete in performing intensive efforts and / or sports performances. In one embodiment, the composition comprises one or more sources of protein, which have a total concentration in the supplement comprised between 40.0 and 80.0%, preferably between 50.0 and 80.0%, more preferably between 60. , 0 and 80.0 m%, even more preferably between 65.0 and 80.0 m%. The composition of the present invention can be formulated in a form adapted to the chosen route of administration, including, but not limited to, oral or parental, including subcutaneous, intramuscular, intraperitoneal, intratumoral, and intravenous, administration. "Oral administration," as defined herein, includes any form of administration in which the composition is taken up through the esophagus of the subject. Oral formulations include any solid, liquid, or powder formulation suitable for use herein, provided such formulation permits the safe and effective oral delivery of the effective dose of 2'-fucosyllactose (2 "-FL).
    In one embodiment, the composition is a soluble powder. The soluble powder has the advantage that the composition can be stored in a suitable container of only limited size and can be dissolved in a liquid by the consumer. The composition not only takes up a small volume, but also has a long shelf life.
    The composition, in one embodiment, is directly ingestible as a capsule. In another embodiment, the composition is ingestible through food products and / or drinks.
    In a preferred embodiment, the composition is a sports drink. A sports drink is very user-friendly for the consumer, as no actions are required by the consumer immediately before intake.
    In this light, the present invention also relates to a method for supporting and / or improving intestinal health in athletes, wherein a composition is administered comprising an effective dose of at least one human milk oligosaccharide (HMO) selected from the group of 2'-fucosyllactose. (2 ”- FL), 3-fucosyllactose (3-FL), lactodifucotetraose (DF-L), lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), lacto-N-fucopentaose I (LNFP I ), lacto-N-difucohexaose II (LNDFH II), lacto-N-neodifucohexaose II (LNnDFH II), para-lacto-N-neohexaose (para-LNnH), lacto-N-neooctaose (LNnO), lacto-N- fucopentaose V (LNFP V), lacto-N-
    neofucopentaose V (LNnFP V), 3 "-sialyl-3-fusoyllactose (F-SL), LS-tetrasaccharide a (LSTa), 3” -sialyllactose (3’-SL), or combinations thereof.
    The effective dose is in one embodiment comprised between 0.5 and 5.0 g / day.
    In particular, the method comprises administering a composition according to any of the preceding embodiments.
    The invention relates in a second aspect, a method for guiding a subject, and / or improving the sports performance and / or recovery of a subject, wherein it is determined whether the subject is a secretor or non-secretor of an HMO. , preferably 2 "-FL, and wherein the subject has a composition comprising an effective dose of at least one human milk oligosaccharide (HMO) selected from the group of 2" -fucosyllactose (2 "-FL), 3-fucosyllactose (3-FL ), lactodifucotetraose (DF-L), lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), lacto-N-fucopentaose I (LNFP I), lacto-N-difucohexaose II (LNDFH II), lacto -N-neodifucohexaose II (LNnDFH II), para-lacto-N-neohexaose (para-LNnH), lacto-N-neooctaose (LNnO), lacto-N-fucopentaose V (LNFP V), lacto-N-neofucopentaose V ( LNnFP V), 3'-sialyl-3-fusoyllactose (F-SL), LS-tetrasaccharide a (LSTa), 3 ”sialyllactose (3" -SL), or combinations thereof.
    Preferably, the HMO comprises 2'-fucosyllactose (2'-FL). In one embodiment, it is determined whether the subject is a secretor or non-secretor of an HMO by checking for the presence or absence of one or more genetic polymorphisms or mutations in the 2-alpha-L-fucosyltransferase 2 (FUT 2) gene.
    In another embodiment, the subject's secretor / non-secretor status is determined by checking for the presence or absence of one or more genetic polymorphisms or mutations in a gene other than the 2-alpha-L-fucosyl transferase 2 (FUT 2) gene.
    In a further or different embodiment, the secretor / non-secretor status of the subject is determined by checking the presence or absence of one or more polymorphisms at the protein level, in particular the protein encoded by the FUT 2 gene.
    The protein encoded by FUT 2 is a Golgi staple membrane protein involved in the production of a precursor to the H antigen required for the final step in the soluble A and B antigen synthesis pathway.
    This gene is one of the two genes that code for the 2-alpha-L-fucosyl transferase 2 enzyme.
    SNPs at the level of the FUT 2 gene and / or polymorphisms in the protein for which this gene codes, give rise to a reduced to absent secretion of 2'-FL and are therefore extremely suitable for determining the secretor / non-secretor status towards 2 ' -FL.
    More preferably, the method comprises a DNA analysis, identifying single nucleotide polymorphisms (SNPs) in the 2-alpha-L-fucosyl transferase 2 (FUT 2) gene.
    The FUT 2 gene is involved in the production of 2'-FL, whereby individuals with an inactivating polymorphism in the FUT2 gene are termed non-secretors.
    Non-secretors are deficient in innate gut carbohydrates containing fucose, which makes them more prone to gut dysbiosis.
    The term “intestinal dysbiosis” herein denotes an imbalance between different microorganisms present in the intestinal system.
    In addition, non-secretors have a higher risk of intestinal disorders such as Crohn's disease.
    Preferably, the single nucleotide polymorphisms (SNPs) include the SNPs rs601338, rs492602, rs516246 and / or rs602662. Such SNP numbering can be consulted on databases such as SNPedia.
    The SNPs of this embodiment are extremely relevant to the non-secretory status of a subject with respect to 2'-FL.
    Preferably, SNP rs601338 is detected, of which 25 to 30% of the population is carriers.
    More preferably, at least 2 SNPs from the group of rs601338, rs492602 and / or rs602662 are detected.
    Even more preferably, rs601338, rs492602 and rs602662 are detected.
    DNA analysis and / or detection of SNPs according to the present invention is done by standard techniques as known in the art.
    Preferably, a microarray, or single nucleotide polymorphism (SNP) chip, is used to identify SNPs present in the FUT 2 gene.
    In one embodiment of the method, the effective dose of the HMO is optionally determined based on the secretor / non-secretor status, comprised between 0.5 and 5.0 g / day.
    The action of HMOs, and in particular 2 ”-FL, is multi-pronged and includes interference in binding of pathogens and toxins, reducing the risk of infections; and improves intestinal motility.
    The various effects are clearly expressed within the range mentioned.
    In one embodiment, the effective dose of the HMO, particularly 2 "-fucosyllactose (2"-FL), at a non-secretor is at least 1.8 g / day.
    Preferably, the effective dose is comprised between 1.8 and 4.0 g / day, which dose is optimally suited for improving gut health in non-secretors of HMOs. The risk of intestinal disorders is generally considerably higher with non-secretors than with secretors. Administration of the effective dose of HMO lowers the risk of bowel disease, by inhibiting pathogens and improving gut motility. The effective dose is preferably between 2.0 and 3.5 g / day, more preferably between 2.0 and 3.0 g / day. One embodiment comprises an effective dose of the HMO, especially 2 "-fucosyllactose (2" -FL), at a secretor of at least 0.8 g / day. Preferably, the effective dose is comprised between 0.8 and 3.0 g / day, more preferably comprised between 1.0 and 2.5 g / day, even more preferably comprised between 1.8 and 2.2 g / day. day. In one embodiment of the method, the effective dose of HMO is administered via a composition according to an embodiment of the first aspect of the invention. The subject, in one embodiment, is an athlete. Since performing intensive training has a major impact on the microbiota, including the microbiome, athletes in particular benefit from a composition and method according to the present invention. Preferably, the athlete has formed a course of antibiotics prior to the method. Following a course of antibiotics has an adverse effect on intestinal health, making the method according to the present invention particularly advantageous. In what follows, the invention is described by means of non-limiting examples illustrating the invention, and which are not intended or should be construed to limit the scope of the invention.
    EXAMPLES The invention will now be further elucidated on the basis of the following examples, without otherwise being limited thereto.
    EXAMPLE 1: Composition for Improving Gut Health
    The following composition is extremely suitable for the improvement and / or support of intestinal health, with a recommended daily dose of 3.0 9 / day. ingredient concentration (m%) 2'-fucosyllactose (2'-FL) 70.00 000 lacto-N-tetraose (LNT) 15.00 lacto-N-fucopentaose V (LNFP V) 10.00 various fillers 5.00
    A Subjects who receive the composition on a daily basis are less prone to infections, feel fitter and experience improved gut motility. EXAMPLE 2: composition for optimizing recovery in endurance athletes The composition shown in the table below optimizes recovery in athletes by supporting intestinal health from a daily dose of 2.5 g / day. ingredient concentration (m%) 2'fucosyllactose (2-FL) 80.00 2222 various fillers 20.00
    EE In 20 endurance athletes who were administered the composition at 2.5 g / day for 60 days, the required recovery time after intensive training was shortened by 5 to 10% compared to the control group (20 subjects). Athletes who were administered the composition experienced fewer abdominal and intestinal complaints during and / or after intensive training and indicated that they felt recovered more quickly. Of the tested athletes, 25% indicated that they were also better able to schedule consecutive intensive training sessions. EXAMPLE 3: Powdered Nutritional Supplement for Athletes The nutritional supplement with composition as shown in the following table is a suitable addition to a healthy diet to improve intestinal health, improve recovery and sports performance.
    ingredient concentration (m%) 2'-fucosyllactose (2 "-FL) 25.00 micronutrients (Zn salt) 0.10 L-glutamine 6.30 vegetable extracts 65.00 various fillers 3.60 The food supplement is powdered and should dissolved in water, milk, orange juice or another drinkable liquid.
    For daily consumption, preferably a dose of 8g is dissolved in a liquid volume of 100 mL.
    Daily consumption improves the functioning of the immune system in athletes, as a result of improved intestinal health.
    In particular, when other supplements are used, in particular supplements comprising fructose and / or artificial sweeteners, optimal intestinal motility is obtained and the risk of pathogenic infections is minimized.
    EXAMPLE 4: protein powder with human milk oligosaccharides The protein powder of the following composition supports an optimal build-up of muscle mass and optimizes the required recovery time between workouts, allowing a higher training volume. ingredient concentration (m%) whey protein 68.00 carbohydrates 16.00 2'-fucosyllactose (2'-FL) 4.50 calcium (Ca) 0.30 potassium (K) 0.40 various additives 10.80 With daily consumption of 45g, preferably immediately after strength training, maximizes the build-up of muscle mass and minimizes the negative side effects of intensive training on the gastrointestinal tract.
    The protein powder is suitable for solution of 200 to 300 ml drinkable liquid.
    The present powder shortens the required recovery time after a workout, which is particularly advantageous if a workout regimen of 4 to 6 sessions per week is envisaged. EXAMPLE 5: Improvement of Gut Health in Non-secretors of HMOs Regarding non-secretors of human milk oligosaccharides, the invention provides a method for improving gut health in these subjects, which goes through the following steps.
    1. Determination of the subject's 2'-fucosyllactose secretor / non-secretor status by detecting the single nucleotide polymorphisms (SNPs) rs601338, rs492602, rs516246 and / or rs602662 at the 2-alpha L-fucosyltransferase 2 (FUT 2) gene and includes the steps: a. Taking a sample from the subject (blood, saliva, urine, hair, skin etc .; b. Isolation and purification of genomic DNA from the blood sample; c. Isolation and purification of a DNA fragment comprising the 2-alpha-L-fucosyltransferase 2 (FUT 2) gene by restriction enzymes; d. optional replication of the relevant DNA fragment by PCR; e. detection of the SNPs by genotyping using a microarray ie a single nucleotide polymorphism (SNP) chip in accordance with the rs601338, rs492602, rs602662 and / or possibly other relevant SNPs; f. if one or more SNPs give a positive result, the subject is characterized as non-secretor, if not subject characterized as a secretor from 2'-FL.
    2. Optional, determination of the effective dose of 2 "-fucosyllactose (2'-FL) based on secretor / non-secretor status: a. For non-secretors a daily dose is comprised between 2.0 and 3.0 g Prescribed in order to minimize the specific risks to which this group is exposed; b.For secretors, a daily dose between 1.8 and 2.2 g / day is prescribed to support normal intestinal health.
    3. Administration of the effective dose of 2 ”-fucosyllactose (2’-FL) to the subject. Depending on the particular secretor / non-secretor status, the subject is administered a dose between 2.25 and 3.75 9 / day of the following composition.
    ingredient concentration (M%) 2'-fucosyllactose (2'-FL) 80.00 various fillers 20.00 This methodology provides for efficient support and / or improvement of gut health in non-secretors of 2'-FL, which have a have a higher chance of developing intestinal disorders such as Crohn's disease.
    The intestinal microbiota is optimally supported and intestinal motility is stimulated.
    This reduces the chance of developing infections and chronic diseases in this target group in the long term.
    权利要求:
    Claims (22)
    [1]
    Composition for use in supporting and / or improving intestinal health in athletes, characterized in that the composition comprises an effective dose of at least one human milk oligosaccharide (HMO) selected from the group of 2 ”-fucosyllactose (2 '). -FL), 3-fucosyllactose (3-FL), lactodifucotetraose (DF-L), lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), lacto-N-fucopentaose I (LNFP I), lacto -N-difucohexaose II (LNDFH II), lacto-N-neodifucohexaose II (LNnDFH II), para-lacto-N-neohexaose (para-LNnH), lacto-N-neooctaose (LNnO), lacto-N-fucopentaose V ( LNFP V), lacto-N-neofucopentaose V (LNnFP V), 3 ”-sialyl-3-fusoyllactose (F-SL), LS-tetrasaccharide a (LSTa), 3” sialyllactose (3 "-SL), or combinations thereof .
    [2]
    Composition for use according to claim 1, characterized in that the human milk oligosaccharide (HMO) comprises 2 "-fucosyllactose (2"-FL).
    [3]
    Composition for use according to claim 1 or 2, characterized in that the human milk oligosaccharide (HMO) is a synthetically produced HMO.
    [4]
    Composition for use according to any one of the preceding claims 1-3, characterized in that the effective dose of the human milk oligosaccharide (HMO) is comprised between 0.5 and 5.0 g / day.
    [5]
    Composition for use according to claim 4, characterized in that the effective dose of the human milk oligosaccharide (HMO) is between 1.8 and 2.2 g / day.
    [6]
    Composition for use according to any one of the preceding claims 1 - 5, characterized in that the athletes have followed a course of antibiotics prior to the administration of the composition.
    [7]
    Composition for use according to any one of the preceding claims 1-6, characterized in that prior to the administration of the composition, it was determined whether the athletes are secretor or non-secretor of said HMO.
    [8]
    Composition for use according to any one of the preceding claims 1-7, characterized in that prior to the administration of the composition the athletes are tested for the presence or absence of one or more genetic polymorphisms or mutations.
    [9]
    Composition for use according to claim 8, characterized in that said polymorphisms or mutations concern the FUT 2 gene.
    [10]
    Composition for use according to any one of the preceding claims 1-9, characterized in that the composition comprises one or more excipients, wherein the HMO and the one or more excipients are in a ratio between 1: 8 and 6 : 8, preferably between 1: 8 and 3: 8.
    [11]
    Composition for use according to claim 10, characterized in that the one 8E2019 / 5134 multiple excipients are selected from the group consisting of amino acids, monosaccharides, micronutrients, vegetable extracts, fibers, derivatives of any of the foregoing excipients, or combinations thereof.
    [12]
    Composition for use according to any one of the preceding claims 1-11, characterized in that the nutritional supplement is a soluble powder.
    [13]
    Composition for use according to any one of the preceding claims 1-11, characterized in that the nutritional supplement is a sports drink.
    [14]
    14. Method of guiding a subject, improving a subject's athletic performance, and / or non-therapeutically improving a subject's recovery, determining whether the subject is a secretor or non-secretor of an HMO , preferably 2'-FL, and wherein the subject has a composition comprising an effective dose of at least one human milk oligosaccharide (HMO) selected from the group of 2'-fucosyllactose (2'-FL), 3-fucosyllactose (3-FL ), lactodifucotetraose (DF-L), lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), lacto-N-fucopentaose I (LNFP I), lacto-N-difucohexaose II (LNDFH II), lacto -N-neodifucohexaose II (LNnDFH II), para-lacto-N-neohexaose (para-LNnH), lacto-N-neooctaose (LNnO), lacto-N-fucopentaose V (LNFP V), lacto-N-neofucopentaose V ( LNnFP V), 3 "-sialyl-3-fusoyllactose (F-SL), LS-tetrasaccharide a (LSTa), 3” -sialyllactose (3'-SL), or combinations thereof.
    [15]
    A method according to claim 14, characterized in that the HMO comprises 2'-fucosyllactose (2'-FL).
    [16]
    Method according to claim 14 or 15, characterized in that it is determined whether the subject is a secretor or non-secretor of an HMO by checking for the presence or absence of one or more genetic polymorphisms or mutations in the 2-alpha -L-fucosyl transferase 2 (FUT 2) gene.
    [17]
    Method according to claim 16, characterized in that the method comprises a DNA analysis, wherein single nucleotide polymorphisms (SNPs) 2-alpha-L-fucosyl transferase 2 (FUT 2) gene are identified.
    [18]
    A method according to claim 17, characterized in that the single nucleotide polymorphisms (SNPs) are rs601338, rs492602, rs516246 and / or rs602662.
    [19]
    A method according to any one of the preceding claims 14-18, characterized in that the effective dose of the HMO for a non-secretor is between 1.8 and 4.0 g / day.
    [20]
    A method according to any one of the preceding claims 14-19, characterized in that the effective dose of the HMO in a secretor is between 0.8 and 3.0 g / day.
    [21]
    A method according to any one of the preceding claims 14-20, characterized in that in dBE2019 / 5134 the subject is an athlete.
    [22]
    22. A method according to claim 21, characterized in that the athlete has previously completed a course of antibiotics.
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    同族专利:
    公开号 | 公开日
    BE1027078A9|2020-09-28|
    EP3930482A1|2022-01-05|
    BE1027078A1|2020-09-17|
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    法律状态:
    2020-10-23| FG| Patent granted|Effective date: 20200921 |
    2021-08-11| PD| Change of ownership|Owner name: NUTRIBAM BV; BE Free format text: DETAILS ASSIGNMENT: CHANGE OF OWNER(S), CHANGE OF LEGAL ENTITY; FORMER OWNER NAME: NUTRIBAM BVBA Effective date: 20210630 |
    优先权:
    申请号 | 申请日 | 专利标题
    BE201905116|2019-02-25|EP20713738.1A| EP3930482A1|2019-02-25|2020-02-25|Composition, food supplement and method for supporting and/or improving intestinal health|
    US17/427,900| US20220022515A1|2019-02-25|2020-02-25|Composition, Food Supplement and Method for Supporting and/or Improving Intestinal Health|
    PCT/IB2020/051589| WO2020174386A1|2019-02-25|2020-02-25|Composition, food supplement and method for supporting and/or improving intestinal health|
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