Oligosaccharide composition for use in gastrointestinal and respiratory discomfort during and / or after an athletic activity

Abstract

An oligosaccharide composition for use in the prevention, amelioration and / or treatment of gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions. The composition comprises oligosaccharide compounds, for example galactooligosaccharide compounds, which includes: (a) at least 8 wt% Gal-(β1-3)-Gal-(β1-4)-Xa; (b) at least 3 wt% Gal-(β1-3)-Gal-(β1-3)-Xb; and (c) at least 5wt% Gal-(β1-3)-Gal-(β1-2)-Xc, based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xb and Xc are each independently selected from monosaccharides. These compositions contain relatively high amounts of the oligosaccharide compounds (a), (b) and (c) and a relatively high amount of β1-3 Gal-Gal linkages, compared to known oligosaccharide compositions. These particular features of the composition are believed to provide benefits to the health of a subject during and / or after athletic activity, for example reducing episodes of URS and GI discomfort and / or damage. A method of preparing said composition and the use of said composition as a dietary supplement or a medicament are also disclosed. Oligosachharide compositions for use in and methods of reducing plasma I-FABP and / or increasing salivary immunoglobulin A (sIgA) during and / or after athletic activity in extreme environmental conditions by administering the oligosaccharide composition according to the present invention are also disclosed.

Description

[0001] OLIGOSACCHARIDE COMPOSITION FOR USE IN GASTROINTESTINAL AND RESPIRATORY DISCOMFORT DURING AND / OR AFTER AN ATHLETIC ACTIVITY

[0002] Field

[0003] The present invention relates to a composition comprising galactooligosaccharides (GOS) for use in reducing adverse gastrointestinal and upper respiratory effects of athletic activity conducted in extreme environmental conditions. The present invention also relates to methods of preparing said compositions and the formulation of said compositions as dietary supplements and / or medicaments. In particular the present invention relates to an oligosaccharide composition with a relatively high amount of certain beneficial oligosaccharides.

[0004] Background

[0005] Gastrointestinal (Gl) complaints are common among athletes from a range of sports. Gl disturbances during exercise activity are well documented across a variety of athletic events and populations. Typical symptoms can include nausea, cramping, bloating and the urgent need to defecate, with severe cases having a detrimental effect on performance. Gl symptoms are thought to be caused by increased splanchnic hypoperfusion seen during exercise. Exercise causes a redistribution of blood flow, whereby blood flow is shunted away from the intestines to aid working skeletal muscle. This increases ischemic stress which disrupts key structural cells within the intestinal barrier. Disruption to these cells can increase the passage of foreign elements and pathogens through the intestinal barrier and into systemic circulation, resulting in inflammation and Gl symptoms. Both high-intensity exercise and endurance exercise has been shown to induce intestinal damage. While the environment and thermal load have also been shown to impact intestinal damage and symptoms.

[0006] It is becomingly increasingly common for team-based athletes to perform in hot climates which may increase the likelihood of gastrointestinal and respiratory illness. Gut microbes have a substantial influence on systemic immune function and gastrointestinal health. Dietary prebiotic galactooligosaccharides are effective at altering the gut microbiome and have been shown to alleviate upper respiratory symptoms (URS) and gastrointestinal symptoms (GIS) in elite rugby union players during a competitive season.

[0007] Football is a team-based sport characterised by repeated bouts of high intensity activity separated by low intensity recovery periods. The prolonged aerobic and intermittent nature of football activity imposes significant thermal loads which elevates core body temperature during match play, changes which are strongly associated with impaired physical skills and cognitive performance across a range of performance metrics independent of performance environment. These responses may be exacerbated when performed in hot environments. Ambient temperatures >32°C place significant stress on the Gl system in relation to thermal load and the maintenance of splanchnic perfusion. It is becoming more popular for football and similar team sports to be performed in hot ambient temperatures, putting them at a greater risk of Gl complaints. Therefore, there is a need to identify interventions that can alleviate Gl damage and symptoms during exercise under extreme (physical) conditions such as in high temperatures, high humidity and / or low oxygen levels.

[0008] There is increasing evidence that dietary interventions of either probiotics (live bacteria) or prebiotics (non-digestible food ingredients) which modify the gut microbiota can help reduce Gl symptoms in athletes. The majority of research has focused upon the supplementation of probiotics. While one study has shown potential performance benefits of probiotics in humans under extreme environmental conditions, there is currently no evidence that concludes that probiotics may directly enhance athletic performance. Furthermore with 1000s of different species of probiotic bacteria there is no consensus on what probiotics are most effective. A suitable alternative may be dietary intervention of a prebiotic that acts as a fertilizer for the growth and activity of beneficial bacteria in the gut.

[0009] Prebiotics are defined by the International Scientific Association for Probiotics and Prebiotics as “a substrate that is selectively utilized by host microorganisms conferring a health benefit”. Most prebiotics are non-digestible dietary fibres that resist digestion and absorption until they reach the large intestine where they are fermented by members of the gut microbiome. They can modify the composition and function of the gut microbiome. A diet rich in prebiotics has been shown to increase gut microbiome gene richness and the abundance of beneficial bacteria such as Bifidobacterium and Lactobacillus. Prebiotics also play multiple roles in suppressing gut pathogens, as an example, members of the Bifidobacterium and Lactobacillus genera produce lactic acid during prebiotic fermentation. Beneficial gut microbes utilise prebiotics as an energy source. As a byproduct of this fermentation, in addition to lactic acid they also produce short-chain fatty acids (SCFAs), such as acetate, butyrate, and propionate. SCFAs are known to have several beneficial effects on human health including maintenance of the colonic epithelium; a potential role in regulating glucose homeostasis, lipid metabolism, and appetite regulation; and a role in regulating the immune system and inflammatory response.

[0010] Galactooligosaccharides (GOS) are an important and well-studied class of prebiotics. GOS has been shown to strongly stimulate the growth of bifidobacteria in the gut, as well as lactobacilli and Bacteroidetes, though to a lesser extent. Bifidobacteria are considered highly beneficial to the human host, primarily for their ability to produce SCFAs. Additionally, they are strongly associated with improvement in the intestinal epithelial barrier and intestinal permeability and play a beneficial role in host immunomodulation.

[0011] Regular consumption of prebiotics has previously been shown to improve markers of immunity and reduce inflammation in the general population and high-risk groups (elderly, obese & asthmatics). Prebiotics have previously been shown to improve respiratory health, lower inflammation and gut damage in obesity and improve anxiety like behaviour in animal models but there is no evidence to date of their use in an athletic setting to improve health following intense exercise under extreme environmental conditions. Summary of the Invention

[0012] It is one aim of the present invention, amongst others, to provide a composition comprising oligosaccharide compounds that addresses at least one disadvantage of the prior art, whether identified here or elsewhere, or to provide an alternative to existing compositions. For instance, it may be an aim of the present invention to provide a composition comprising oligosaccharide compounds which comprise a higher proportion of specific beneficial oligosaccharides than known oligosaccharide compositions.

[0013] According to aspects of the present invention, there is provided a composition, method and use as set forth in the appended claims. Other features of the invention will be apparent from the dependent claims, and from the description which follows.

[0014] According to a first aspect of the present invention, there is provided a composition comprising oligosaccharide compounds for use in the prevention, amelioration and / or treatment of gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions, wherein the oligosaccharide compounds comprise:

[0015] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0016] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0017] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc, based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xband Xcare each independently selected from monosaccharides.

[0018] In an embodiment related to the first aspect of the present invention, there is also provided a method of preventing, ameliorating or treating gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions, which comprises the administration of a composition comprising oligosaccharide compounds to a subject in need of such prevention, amelioration and / or treatment, wherein the oligosaccharide compounds comprise:

[0019] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0020] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0021] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc, based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xband Xcare each independently selected from monosaccharides.

[0022] In an embodiment related to the first aspect of the present invention, there is also provided a method of preventing, ameliorating or treating gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions in a subject in need of such prevention, amelioration and / or treatment the method comprising: i) administrating a therapeutically effective amount of a composition comprising oligosaccharide compounds to the subject, wherein the oligosaccharide compounds comprise:

[0023] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0024] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0025] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc, based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xband Xcare each independently selected from monosaccharides.

[0026] In a further embodiment of the present invention, there is provided the use of a composition for the manufacture of a medicament for the prevention, amelioration and / or treatment of gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions, wherein the composition comprises oligosaccharide compounds, said oligosaccharide compounds comprising:

[0027] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0028] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0029] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc, based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xband Xcare each independently selected from monosaccharides. In a further aspect of the present invention there is provided a composition comprising oligosaccharide compounds for use in the reduction of plasma l-FABP during and / or after athletic activity in extreme environmental conditions, wherein the oligosaccharide compounds comprise:

[0030] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0031] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0032] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc, based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xband Xcare each independently selected from monosaccharides.

[0033] There is also provided a method of reducing plasma l-FABP during and / or after athletic activity in extreme environmental conditions, which comprises the administration of a composition comprising oligosaccharide compounds to a subject, wherein the oligosaccharide compounds comprise:

[0034] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0035] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0036] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc, based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xband Xcare each independently selected from monosaccharides.

[0037] There is also provided a method of reducing plasma l-FABP during and / or after athletic activity in extreme environmental conditions in a subject the method comprising: i) administrating a therapeutically effective amount of a composition comprising oligosaccharide compounds to the subject, wherein the oligosaccharide compounds comprise:

[0038] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0039] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0040] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc, based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xband Xcare each independently selected from monosaccharides. There is also provided the use of a composition for the manufacture of a medicament for the reduction of plasma l-FABP during and / or after athletic activity in extreme environmental conditions, wherein the composition comprises oligosaccharide compounds, said oligosaccharide compounds comprising:

[0041] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0042] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0043] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc, based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xband Xcare each independently selected from monosaccharides.

[0044] Plasma intestinal fatty acid binding protein (l-FABP) is a gut barrier integrity marker and a systemic marker of Gl damage. l-FABP may be measured in the blood plasma of a subject. The l-FABP may be measured as the peak plasma l-FABP and compared to a control sample to determine if there has been a reduction in l-FABP. The control sample may be from a subject who has not received the composition according to the present invention such as a subject who has received no oligosaccharide composition or who may have received a placebo composition such as maltodextrin. The reduction in plasma l-FABP may also be measured by comparing the peak plasma l-FABP before administration of the composition according to the present invention to the peak plasma I- FABP at any time post administration of the composition according to the present invention. The level of l-FABP may be determined by measuring l-FABP before administering the composition according to the present invention or placebo and before athletic activity has taken place. Further samples may be taken after administering the composition or placebo according to the present invention and during and / or after athletic activity has taken place. Alternatively in a subject who has not received either the composition according to the present invention or a placebo, a sample may be taken before athletic activity has taken place.

[0045] The reduction in l-FABP during and / or after athletic activity in a subject who has been administered the composition of the present invention may be a 1-50% reduction in l-FABP compared to a control subject. In particular, there may be a 10-35% reduction in l-FABP compared to a control subject. There may be a 30% reduction in l-FABP compared to a control subject. The composition according to the present invention may have been administered to a subject before athletic activity.

[0046] The reduction in l-FABP during and / or after athletic activity in a subject who has been administered the composition of the present invention for 42 days may be a 1-50% reduction in l-FABP compared to levels of l-FABP pre-administration of the composition according to the present invention. In particular, there may be a 10-35% reduction in l-FABP compared to levels of l-FABP preadministration of the composition according to the present invention. There may be a 30% reduction in l-FABP compared to levels of l-FABP pre-administration of the composition according to the present invention. l-FABP is expressed in epithelial cells of the mucosal layer of the small intestinal tissue. When intestinal mucosal damage occurs l-FABP is released into the circulation and therefore the plasma l-FABP concentration increases. A lower or reduced l-FABP level or concentration is therefore indicative of good or improved gut barrier integrity.

[0047] In a further aspect of the present invention there is provided a composition comprising oligosaccharide compounds for use in the increase of saliva immunoglobulin A (slgA) during and / or after athletic activity in extreme environmental conditions, wherein the oligosaccharide compounds comprise:

[0048] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0049] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0050] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc, based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xband Xcare each independently selected from monosaccharides.

[0051] There is also provided a method of increasing saliva immunoglobulin A (slgA) during and / or after athletic activity in extreme environmental conditions, which comprises the administration of a composition comprising oligosaccharide compounds to a subject, wherein the oligosaccharide compounds comprise:

[0052] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0053] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0054] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc, based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xband Xcare each independently selected from monosaccharides.

[0055] In a further aspect of the present invention, there is also provided a method of increasing saliva immunoglobulin A (slgA) during and / or after athletic activity in extreme environmental conditions in a subject the method comprising: i) administrating a therapeutically effective amount of a composition comprising oligosaccharide compounds to the subject, wherein the oligosaccharide compounds comprise:

[0056] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0057] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0058] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc, based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xband Xcare each independently selected from monosaccharides.

[0059] There is also provided the use of a composition for the manufacture of a medicament for the increase of saliva immunoglobulin A (slgA) during and / or after athletic activity in extreme environmental conditions, wherein the composition comprises oligosaccharide compounds, said oligosaccharide compounds comprising:

[0060] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0061] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0062] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc, based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xband Xcare each independently selected from monosaccharides. slgA is a marker of immune function. The increase in slgA may be an increase compared to a control subject. The control subject is a subject who has not received the composition according to the present invention. The control subject may have received no oligosaccharide composition or may have been administered a placebo composition such as maltodextrin. The increase in slgA may also be measured by comparing the level of slgA before exercise with the level during and / or after exercise priorto administration of the composition according to the present invention, with the change in level of slgA during and / or after exercise vs. before at any time post administration of the composition according to the present invention. For instance, the level of slgA may be measured before and during and / or after exercise prior to and 42 days post administration of the composition according to the present invention.

[0063] An increase in slgA may be determined by comparing slgA levels in a subject who has been administered the composition according to the present invention compared to slgA levels in a subject who has not received the composition according to the present invention. slgA is an antibody and its levels are a marker of mucosal immune function. slgA is a mediator of local immunity and host defence. slgA is a secreted immunoglobulin from the mucosa that can trap and neutralise bacteria, viruses and toxins. High-intensity physical exercise has been shown to decrease slgA levels thus resulting in an increased risk of infection. A higher slgA level compared to a control subject is indicative of better (aspecific or innate) immune health and improved first line of defence and protection against infection. The composition according to the present invention may have been administered to a subject before athletic activity.

[0064] There is also provided a composition for use according to the above aspects and embodiments, for administration to any person or an athlete or sports person who is undergoing and / or about to undergo, physical training. The composition for use according to the above embodiments, may be for administration to any person who is undergoing and / or about to undergo, physical training. The composition for use according to the above embodiments, may be for administration to any person or athlete or sports person who is undergoing and / or about to undergo, physical training in extreme environmental conditions.

[0065] There is also provided a composition for use according to the above aspects and embodiments, for administration to any person or an athlete or sports person who is undergoing and / or about to undergo, athletic activity. The composition for use according to the above embodiments, may be for administration to any person who is undergoing and / or about to undergo, athletic activity. The composition for use according to the above embodiments, may be for administration to any person or athlete or sports person who is undergoing and / or about to undergo, athletic activity in extreme environmental conditions.

[0066] The composition may be in the form of a spray-dried powder, a tablet, a capsule, a liquid formulation such as a syrup, or a soft pastille. The product known as Bimuno comprises at least 49% of the dry matter as the mixture of galactooligosaccharides. The remainder of the composition may comprise non-active components such as glucose, galactose, and lactose.

[0067] The powder composition preferably comprises up to about 80% galactooligosaccharides of the powdered composition.

[0068] The powder composition preferably comprises from about 1.35g to about 10g of galactooligosaccharides in about 1.83g to about 13.16g of the powdered composition, preferably from about 2g to about 5g of galactooligosaccharides in about 2.63g to about 6.58g of the powder, most preferably about 2.0g to about 2.75g of galactooligosaccharides in about 2.63g to about 3.65g of composition. The daily dosage of the composition comprising oligosaccharide compounds may be 3.65g wherein it comprises 2.75g of active oligosaccharides.

[0069] The composition may be added to a drink, preferably a hot drink, or sprinkled on food, for example, on breakfast cereal. The composition may also be added as an ingredient to various foodstuffs and drinks such as fruit juice, fruit drinks, water, coffee, yoghurt, cereals, bread, cakes, biscuits and the like.

[0070] The composition comprising oligosaccharides may be administered in a single dose. The composition comprising oligosaccharides may be administered in a single daily dose. The composition comprising oligosaccharides may be administered in a single dose at any time during a 24-hour period. The composition comprising oligosaccharides may be administered in multiple doses at any time during a 24-hour period. The composition may be administered alone or mixed with food and / or drink. The composition comprising oligosaccharides may be administered orally.

[0071] As used herein, the terms "treatment", "treating", “treat” and the like, refer to obtaining a desired pharmacologic and / or physiologic effect. The effect can be prophylactic in terms of completely or partially preventing a disease or symptom thereof and / or can be therapeutic in terms of a partial or complete cure for a disease and / or adverse effect attributable to the disease. "Treatment" as used herein, covers any treatment of a disease in a mammal, particularly in a human, and includes: (a) preventing the disease from occurring in a subject which can be predisposed to the disease but has not yet been diagnosed as having it; (b) inhibiting the disease, i.e., arresting or slowing its development; and (c) relieving the disease and / or symptoms of the disease, i.e., causing regression of the disease.

[0072] The term “gastrointestinal discomfort” refers to any adverse gastrointestinal symptom such as bloating, flatulence, the urgent need to defecate, the urge to vomit, nausea and cramping.

[0073] The term “gastrointestinal damage” refers to any negative effects on the gastrointestinal environment. Changes in gastrointestinal permeability and inflammation are examples of gastrointestinal damage. Such damage may be indicated by the presence of systemic markers of gastrointestinal damage (e.g. I-FABP), permeability (e.g. LBP, Claudin-3), and / or inflammation (e.g. CRP, TNF-a, IL-6, IL-10). The term “gastrointestinal damage” includes damage to, and function of, the gut barrier. I-FABP is a marker for gut barrier leakage and / or gut barrier integrity.

[0074] The term “upper respiratory episodes” refers to a range of conditions and / or diseases associated with the upper respiratory tract with identifiable symptoms, including but not limited to the following respiratory conditions and / or diseases: bacterial infections, viral infections, colds, influenza (flu), respiratory allergies and asthma. The term “upper respiratory episodes” also includes symptoms such as a sore throat, catarrah (excessive mucus) in the throat, runny nose, cough and repetitive sneezing.

[0075] The prevention, amelioration and / or treatment of upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions may include a reduction in the duration of an upper respiratory episode and / or a reduction in the severity of an upper respiratory episode in a subject who has been administered the composition according to the present invention compared to a subject who has not received the composition according to the present invention, for instance a subject who has received a placebo.

[0076] The gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes may occur during and / or after athletic activity. For instance, the gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes may occur whilst the subject is actively participating in the athletic activity. The gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes may also occur immediately following the athletic activity and up to and including 1 hour, 2 hours, 3 hours, 4 hours, 5 hours or 6 hours following the end of the athletic activity. The gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes may also occur at any time during a 24-hour period after the end of the athletic activity. The gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes may also occur at any time during a 42-day period after the end of the athletic activity.

[0077] The term “athletic activity” refers to any physical activity or training carried out by a subject. For instance, the athletic activity may include walking, running and participation in any team or individual sports. The athletic activity may include playing football, rugby, tennis, cricket, squash or any other sport involving physical activity.

[0078] The term “extreme environmental conditions” refers to, for instance, extreme temperatures, extreme humidity levels and extreme oxygen levels which place a physical and / or mental stress on a human subject. The term “extreme environmental conditions” encompasses hot conditions, cold conditions, high humidity conditions and low oxygen conditions. The “extreme environmental conditions” relate to any external environment conditions experienced by a subject and may be the conditions of an outdoors environment or those of an indoors environment. The extreme environmental conditions of an indoor environment may be artificially generated and / or controlled. Outdoors extreme environmental conditions may comprise high altitude resulting in low oxygen conditions. Outdoors extreme environmental conditions may be experienced in known hot, cold and / or humid climates. The term “extreme environmental conditions” may apply to conditions in which the temperature is 32°C or above.

[0079] The term “hot conditions” refers to temperatures including and above 30°C. The temperature may be 32°C or above. The temperature of the conditions may be that of the ambient conditions or an artificially generated and controlled temperature.

[0080] The term “cold conditions” refers to temperatures including and below 0°C. The temperature of the conditions may be that of the ambient conditions or an artificially generated and controlled temperature.

[0081] The term “high humidity conditions” refers to a humidity level of greater than 50%. High humidity conditions may comprise a relative humidity level of 50% or more. The high humidity conditions may comprise a relative humidity level of 70% or more. For example, relative humidity is the measure of an amount of moisture present in the air compared to the maximum amount of moisture the air can hold at a given temperature, expressed as a percentage. A dewpoint temperature of 13°C and below is considered to be comfortable. A dewpoint of 16-21 °C may be considered heavy, oppressive and uncomfortable.

[0082] The term “low oxygen conditions”, or “hypoxia”, refers to environmental conditions wherein the partial pressure of Oxygen is at or below 75 mmHg. A normal atmosphere contains between 20.8 and 21 % oxygen. The US Occupational Safety and Health Administration (OSHA) defines an oxygen deficient environment as any atmosphere that contains less than 19.5% oxygen. Atmospheric hypoxia occurs naturally at high altitudes.

[0083] The term “subject” used herein includes any human or nonhuman animal. The term “nonhuman animal” includes all mammals, such as nonhuman primates, sheep, dogs, cats, cows, horses.

[0084] A “therapeutically effective amount” refers to the amount of compounds, when administered to a subject for treating a disease, is sufficient to effect such treatment for the disease. The “therapeutically effective amount” will vary depending on the compound(s) used, the disease and its severity and the age, weight, etc., of the subject to be treated.

[0085] The term “performance” refers to the ability of an individual to perform certain physical tasks associated with sports and exercise, including, but not limited to reducing fatigue and improving endurance.

[0086] The term “athlete” or “sports person” refers to an individual actively engaged in sports or exercise, including individuals who are professionals or amateurs.

[0087] The present inventors have advantageously and unexpectedly found that supplementation using the composition of the invention reduced markers of gastrointestinal damage and gastrointestinal symptoms during and following exercise in extreme environmental conditions. Exercise was conducted under hot conditions. The gastrointestinal symptoms monitored included overall Gl discomfort, upper Gl symptoms, lower Gl symptoms and other Gl symptoms. Gl symptoms may include bloating, flatulence and the urge to vomit. The inventors also found that there was a reduction in the duration of and the severity of upper respiratory episodes in subjects administered the GOS composition of the present invention.

[0088] The types of oligosaccharides of the present invention having the specified linkages between the galactose units (denoted Gal) and terminal monosaccharides are believed to be particularly beneficial for the maintenance of a healthy human gut microbiota and therefore beneficial to the health of a subject. Known oligosaccharide compositions either do not contain each of these types of oligosaccharides or contain lower amounts of these oligosaccharides. Therefore the compositions of this first aspect are believed to provide advantages to the consumer in the establishment and maintenance of human gut microbiota when used as prebiotics.

[0089] The weight percentages of the specific oligosaccharide compounds discussed herein are based on the weight of all of the oligosaccharide compounds present in the whole composition. Therefore only the fraction of the composition which is provided by oligosaccharides, either components (a), (b), (c) or any other oligosaccharide present, is taken into account when determining the specified weight percentages. For this determination of oligosaccharide content, disaccharides are included, apart from lactose. The composition of this first aspect may contain other non-oligosaccharide components, including monosaccharides and lactose. These components are not taken into account when determining the specified weight percentages of the oligosaccharide compounds discussed herein. The specified amounts of oligosaccharide compounds in the composition can be referred to as a weight percentage of the oligosaccharide fraction of the composition of this first aspect.

[0090] Oligosaccharide compounds (a), (b) and (c) comprise Xa, Xband Xcrespectively, which are each independently selected from saccharides. The Xa, Xband Xcgroups may be considered to be saccharide units. Therefore the groups Xa, Xband Xccan be considered terminal sugars of the oligosaccharide compounds. The groups Xa, Xband Xcare suitably independently selected from monosaccharides. Any suitable monosaccharide unit which can form oligosaccharides with the galactose units of compounds (a), (b) and (c) can provide Xa, Xband Xc. Suitably Xa, Xband Xcare each independently selected from the following monosaccharides. Suitable monosaccharide units are selected from glucose (Glc), fucose (Fuc), arabinose (Ara), xylose (Xyl), rhamnose (Rha), mannose (Man), galactose (Gal), ribose (Rib), lyxose (Lyx), allose (All), altrose (Alt), gulose (Gul), idose (Ido), talose (Tai), psicose (Psi), fructose (Fru), sorbose (Sor), tagatose (Tag), galactosamine (GalN), glucosamine (GlcN) and N-Acetylglucosamine (GIcNAc) or a mixture thereof. Therefore, each of compounds (a), (b) and (c) may comprise a mixture of oligosaccharide compounds having different respective X groups, for example either Glc or Fuc X groups.

[0091] In some embodiments, groups Xa, Xband Xcare independently selected from the monosaccharides listed above, suitably independently selected from Glc, Fuc, Ara, Xyl, Rha and Man or a mixture thereof.

[0092] The saccharide units of the oligosaccharides in the composition of this first aspect may have either the D or the L enantiomeric form. Suitably the Gal saccharide units in components (a), (b) and (c) all have the D enantiomeric form. The components (a), (b) and (c) may therefore be as follows:

[0093] (a) D-Gal-(|31 -3)-D-Gal-(p1 -4)-Xa;

[0094] (b) D-Gal-(p1-3)-D-Gal-(p1-3)-Xb; and

[0095] (c) D-Gal-(|31 -3)-D-Gal-(|31 -2)-Xc. Suitably the Gal and the Xa, Xband Xcsaccharide units all have the D enantiomeric form. The components (a), (b) and (c) may therefore be as follows:

[0096] (a) D-Gal-(|31 -3)-D-Gal-(p1 -4)-D-Xa;

[0097] (b) D-Gal-(p1-3)-D-Gal-(p1-3)-D-Xb; and

[0098] (c) D-Gal-(P1 -3)-D-Gal-(pi -2)-D-Xc.

[0099] In some embodiments, each of Xa, Xband Xcare Glc. Therefore compounds (a), (b) and (c) may be galactooligosaccharide compounds (GOS) and the composition of this first aspect may be referred to as a galactooligosaccharide composition. Such galactooligosaccharides may be formed by converting lactose to the stated oligosaccharides with a suitable galactosidase enzyme. In such embodiments the components (a), (b) and (c) are suitably as follows:

[0100] (a) Gal-(pi-3)-Gal-(pi-4)-Glc;

[0101] (b) Gal-(pi-3)-Gal-(pi-3)-Glc; and

[0102] (c) Gal-(pi-3)-Gal-(pi-2)-Glc.

[0103] Suitably the Gal and the Glc saccharide units all have the D enantiomeric form. The components (a), (b) and (c) may therefore be as follows:

[0104] (a) D-Gal-(P1 -3)-D-Gal-(p1 -4)-D-Glc;

[0105] (b) D-Gal-(pi-3)-D-Gal-(pi-3)-D-Glc; and

[0106] (c) D-Gal-(P1 -3)-D-Gal-(pi -2)-D-Glc.

[0107] In some embodiments, each ofXa, Xband Xcare a mixture of Glc and one or more of other saccharide units described above, for example Fuc, Ara, Xyl, Rha and Man. Therefore each of (a), (b) and (c) may comprise a mixture of oligosaccharide compounds having either Glc or one of the other saccharide units described above as the X group. In such embodiments, components (a), (b) and

[0108] (c) may be formed by converting a mixture of lactose and an appropriate additional sugar, for example a monosaccharide selected from fucose, arabinose, xylose, rhamnose and mannose, to the oligosaccharides. Suitably each of Xa, Xband Xcare a mixture of Glc and Fuc.

[0109] Other oligosaccharides in the composition comprising oligosaccharide compounds of this first aspect, besides components (a), (b) and (c) discussed above, may also comprise the saccharide unit “X” groups referred to above. The composition of this first aspect comprises (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa. Suitably the composition comprises at least 9 wt% of component (a) or at least 10 wt% of component (a).

[0110] Suitably the composition comprises up to 35 wt% of component (a), up to 30 wt% of component (a) or up to 25 wt% of component (a).

[0111] Suitably the composition comprises from 8 to 35 wt% of component (a), from 8 to 25 wt% of component (a) or from 10 to 20 wt% of component (a).

[0112] The composition of this first aspect comprises (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb. Suitably the composition comprises at least 4 wt% of component (b) or at least 5 wt% of component (b).

[0113] Suitably the composition comprises up to 25 wt% of component (b), up to 20 wt% of component (b) or up to 15 wt% of component (b).

[0114] Suitably the composition comprises from 3 to 25 wt% of component (b), from 4 to 20 wt% of component (b) or from 4 to 10 wt% of component (b).

[0115] The composition of this first aspect comprises (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc. Suitably the composition comprises at least 6 wt% of component (c).

[0116] Suitably the composition comprises up to 25 wt% of component (c), up to 20 wt% of component (c) or up to 15 wt% of component (c).

[0117] Suitably the composition comprises from 5 to 25 wt% of component (c), from 5 to 20 wt% of component (c) or from 6 to 10 wt% of component (c).

[0118] The above amounts are based on the total weight of oligosaccharide compounds present in the composition.

[0119] Suitably in the composition of this first aspect: component (a) is present in an amount up to 35 wt%; component (b) is present in an amount up to 25 wt%; and component (c) is present in an amount up to 25 wt%; based on the total weight of oligosaccharide compounds present in the composition.

[0120] Suitably in the composition of this first aspect: component (a) is present in an amount from 8 to 25 wt%; component (b) is present in an amount from 3 to 25 wt%; and component (c) is present in an amount from 5 to 20 wt%; based on the total weight of oligosaccharide compounds present in the composition.

[0121] In some embodiments, the composition of this first aspect comprises:

[0122] (a) from 8 to 25 wt% Gal-(p1-3)-Gal-(p1-4)-Glc;

[0123] (b) from 3 to 25 wt% Gal-(p1-3)-Gal-(p1-3)-Glc; and

[0124] (c) from 5 to 20 wt% Gal-(p1-3)-Gal-(p1-2)-Glc, based on the total weight of oligosaccharide compounds present in the composition.

[0125] Suitably the ratio of the wt% of compound (a) to compound (b) is from 1 :1 to 3:1 , suitably from 1 .5:1 to 2.5:1 .

[0126] Suitably the ratio of the wt% of compound (a) to compound (c) is from 1 :1 to 3:1 , suitably from 1 .5:1 to 2.5:1.

[0127] Suitably the ratio of the wt% of compound (b) to compound (c) is from 2:1 to 1 :2, suitably from 1 .5:1 to 1 :1.5.

[0128] Suitably, in the composition of this first aspect, the oligosaccharide compounds comprise:

[0129] (d) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd, based on the total weight of oligosaccharide compounds present in the composition; wherein Xd, is selected from saccharides.

[0130] Xdmay be selected from the same monosaccharide units described above for Xa, Xband Xc.

[0131] In some embodiments, Xdis Glc.

[0132] Suitably the Gal saccharide units of component (d) have the D enantiomeric form. Suitably the Gal and the Xdsaccharide units all have the D enantiomeric form. The components (d) may therefore be as follows: D-Gal-(p1-3)-D-Gal-(p1-3)-D-Gal-(p1-4)-D-Xd.

[0133] In some embodiments, Xdis a mixture of Glc and one or more of other monosaccharide units, for example Fuc, Ara, Xyl, Rha and Man, suitably Fuc. Suitably the composition comprises at least 4 wt% of component (d) or at least 5 wt% of component (d).

[0134] Suitably the composition comprises up to 25 wt% of component (d), up to 20 wt% of component (d) or up to 15 wt% of component (d).

[0135] Suitably the composition comprises from 3 to 25 wt% of component (d), from 4 to 20 wt% of component (d) or from 4 to 10 wt% of component (d).

[0136] Suitably in the composition of this first aspect: component (a) is present in an amount from 8 to 25 wt%; component (b) is present in an amount from 3 to 25 wt%; component (c) is present in an amount from 5 to 20 wt%; and component (d) is present in an amount from 3 to 25 wt%; based on the total weight of oligosaccharide compounds present in the composition.

[0137] In some embodiments, the composition of this first aspect comprises:

[0138] (a) from 8 to 25 wt% Gal-(p1-3)-Gal-(p1-4)-Glc;

[0139] (b) from 3 to 25 wt% Gal-(p1-3)-Gal-(p1-3)-Glc;

[0140] (c) from 5 to 20 wt% Gal-(p1-3)-Gal-(p1-2)-Glc, and

[0141] (d) from 3 to 25 wt% Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Glc, based on the total weight of oligosaccharide compounds present in the composition.

[0142] Suitably, in the composition of this first aspect, the oligosaccharide compounds comprise:

[0143] (e) at least 5 wt% Gal-(p1-4)-Gal-(p1-4)-Xe; based on the total weight of oligosaccharide compounds present in the composition; wherein Xeis selected from monosaccharides.

[0144] Xemay be selected from the same monosaccharide units described above for Xa, Xband Xc. Suitably the Gal saccharide units of component (e) have the D enantiomeric form. Suitably the Gal and the Xesaccharide units all have the D enantiomeric form. The components (e) may therefore be as follows: D-Gal-(p1-4)-D-Gal-(p1-4)-D-Xe.

[0145] In some embodiments, Xeis Glc.

[0146] In some embodiments, Xeis a mixture of Glc and one or more of other monosaccharide units, for example Fuc, Ara, Xyl, Rha and Man, suitably Fuc.

[0147] Suitably the composition comprises at least 6 wt% of component (e) or at least 7 wt% of component (e).

[0148] Suitably the composition comprises up to 25 wt% of component (e), up to 20 wt% of component (e) or up to 15 wt% of component (e).

[0149] Suitably the composition comprises from 5 to 25 wt% of component (e), from 5 to 20 wt% of component (e) or from 6 to 10 wt% of component (e).

[0150] Suitably in the composition of this first aspect: component (a) is present in an amount from 8 to 25 wt%; component (b) is present in an amount from 3 to 25 wt%; component (c) is present in an amount from 5 to 20 wt%; component (d) is present in an amount from 3 to 25 wt%; and component (e) is present in an amount from 5 to 25 wt%; based on the total weight of oligosaccharide compounds present in the composition.

[0151] In some embodiments, the composition of this first aspect comprises:

[0152] (a) from 8 to 25 wt% Gal-(p1-3)-Gal-(p1-4)-Glc;

[0153] (b) from 3 to 25 wt% Gal-(p1-3)-Gal-(p1-3)-Glc;

[0154] (c) from 5 to 20 wt% Gal-(p1-3)-Gal-(p1-2)-Glc, and

[0155] (d) from 3 to 25 wt% Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Glc, and

[0156] (e) from 5 to 25 wt% Gal-(p1-4)-Gal-(p1-4)-Glc; based on the total weight of oligosaccharide compounds present in the composition.

[0157] In the compositions of this first aspect, Xa, Xb, Xc, Xdand Xeare each independently selected from the monosaccharides described above.

[0158] In the compositions of this first aspect, Xa, Xb, Xc, Xdand Xemay each be independently selected from Glc, Fuc, Ara, Xyl, Rha and Man or a mixture thereof.

[0159] In some embodiments, Xa, Xb, Xc, Xdand Xeare each Glc.

[0160] In some embodiments, Xa, Xb, Xc, Xdand Xeeach comprise Fuc. Suitably Xa, Xb, Xc, Xdand Xeare each a mixture of Glc and Fuc.

[0161] The oligosaccharide compounds of the compositions of this first aspect suitably have a relatively high proportion of p1 -3 Gal-Gal linkages - mainly due to the presence of the components (a), (b), (c) and optionally (d) in the proportions discussed herein. The inventors have found that such relatively high proportions of p1-3 Gal-Gal linkages may be particularly advantageous for the uses of the composition discussed herein.

[0162] Suitably from 35 to 55% of the Gal-Gal linkages in the oligosaccharide compounds are 1-3 linkages, suitably from 40 to 55%, suitably from 40 to 50%.

[0163] Suitably from 40 to 60% of the Gal-Gal linkages in the oligosaccharide compounds are 1-4 linkages, suitably from 45 to 55%, suitably from 45 to 52%.

[0164] Suitably from 8 to 20% of the Gal-X linkages in the oligosaccharide compounds are 1-3 linkages, suitably from 10 to 18%, suitably from 12 to 16%, suitably wherein X is Glc.

[0165] Suitably from 15 to 25% of the Gal-X linkages in the oligosaccharide compounds are 1-4 linkages, suitably from 16 to 24%, suitably from 17 to 22%, suitably wherein X is Glc.

[0166] Suitably from 30 to 45% of the Gal-X linkages in the oligosaccharide compounds are 1-2 linkages, suitably from 32 to 43%, suitably from 34 to 41 %, suitably wherein X is Glc.

[0167] Suitably from 20 to 36% of the Gal-X linkages in the oligosaccharide compounds are 1-6 linkages, suitably from 22 to 34%, suitably from 25 to 32%, suitably wherein X is Glc.

[0168] Suitably the Gal-X, linkages referred to above, for example Gal-Glu and Gal-Gal linkages, are p linkages, i.e. p-glycosidic bonds. Suitably the composition comprises at least 25 wt% of trisaccharides, based on the total weight of oligosaccharides in the composition. Suitably the composition comprises at least 28 wt% of trisaccharides or at least 30 wt% of trisaccharides.

[0169] Suitably the composition comprises up to 70 wt% of trisaccharides, suitably up to 60 wt% trisaccharides or up to 50 wt% trisaccharides.

[0170] Suitably the composition comprises from 25 to 70 wt% of trisaccharides, suitably from 30 to 60 wt% trisaccharides or from 30 to 50 wt% trisaccharides.

[0171] Suitably the composition comprises at least 10 wt% of tetrasaccharides, based on the total weight of oligosaccharides in the composition. Suitably the composition comprises at least 12 wt% of tetrasaccharides or at least 15 wt% of tetrasaccharides. Suitably the composition comprises at least 20 wt% tetrasaccharides or at least 25 wt% tetrasaccharides.

[0172] Suitably the composition comprises up to 40 wt% of tetrasaccharides, suitably up to 25 wt% tetrasaccharides or up to 20 wt% tetrasaccharides.

[0173] Suitably the composition comprises from 10 to 40 wt% of tetrasaccharides, suitably from 10 to 30 wt% tetrasaccharides or from 12 to 25 wt% tetrasaccharides.

[0174] Suitably the composition comprises from 30 to 50 wt% trisaccharides and from 10 to 25 wt% tetrasaccharides, based on the total weight of the composition.

[0175] As mentioned above, the determination of disaccharides present in the composition excludes lactose Therefore in some embodiments the composition suitably comprises up to 40 wt% of disaccharides, suitably up to 30 wt% disaccharides or up to 20 wt% disaccharides. Suitably the content of lactose in the composition of this first aspect is minimised. Suitably the composition is substantially free of lactose. Suitably the composition does not contain lactose.

[0176] Suitably the composition comprises from 10 to 40 wt% of disaccharides, suitably from 10 to 30 wt% disaccharides or from 10 to 20 wt% disaccharides.

[0177] Suitably the composition comprises from 10 to 40 wt% disaccharides, from 30 to 60 wt% trisaccharides and from 10 to 25 wt% tetrasaccharides, based on the total weight of the composition.

[0178] The following description relates to the content of disaccharides in the oligosaccharide compounds. Suitably the oligosaccharide compounds comprise up to 40 wt% of disaccharides, suitably up to 30 wt% disaccharides or up to 20 wt% disaccharides.

[0179] Suitably the oligosaccharide compounds comprise from 0 to 40 wt% of disaccharides, suitably from 10 to 30 wt% disaccharides or from 10 to 20 wt% disaccharides. Suitably the oligosaccharide compounds comprise at least 25 wt% of trisaccharides, based on the total weight of oligosaccharide compounds present in the composition. Suitably the oligosaccharide compounds comprise at least 30 wt% of trisaccharides or at least 33 wt% of trisaccharides.

[0180] Suitably the oligosaccharide compounds comprise up to 75 wt% of trisaccharides, suitably up to 65 wt% trisaccharides or up to 55 wt% trisaccharides.

[0181] Suitably the oligosaccharide compounds comprise from 25 to 75 wt% of trisaccharides, suitably from 30 to 65 wt% trisaccharides or from 34 to 55 wt% trisaccharides.

[0182] Suitably the oligosaccharide compounds comprise at least 10 wt% of tetrasaccharides, based on the total weight of oligosaccharide compounds present in the composition. Suitably the oligosaccharide compounds comprise at least 12 wt% of tetrasaccharides or at least 15 wt% of tetrasaccharides.

[0183] Suitably the oligosaccharide compounds comprise up to 45 wt% of tetrasaccharides, suitably up to 35 wt% tetrasaccharides or up to 30 wt% tetrasaccharides.

[0184] Suitably the oligosaccharide compounds comprise from 10 to 45 wt% of tetrasaccharides, suitably from 10 to 35 wt% tetrasaccharides or from 15 to 30 wt% tetrasaccharides.

[0185] Suitably the oligosaccharide compounds comprise from 0 to 40 wt% disaccharides and from 30 to 75 wt% trisaccharides, based on the total weight of oligosaccharide compounds present in the composition.

[0186] Suitably the oligosaccharide compounds comprise from 0 to 40 wt% disaccharides, from 30 to 75 wt% trisaccharides and from 10 to 45 wt% tetrasaccharides, based on the total weight of oligosaccharide compounds present in the composition.

[0187] The composition of this first aspect suitably comprises at least 50 wt% of oligosaccharide compounds, including components (a), (b), (c) and optionally (d) and (e). Suitably the composition comprises at least 55 wt% of oligosaccharide compounds, suitably at least 60 wt%, based on the total weight of the composition.

[0188] Suitably the composition comprises up to 100 wt% oligosaccharide compounds, suitably up to 95 wt%, up to 90 wt% or up to 85 wt% oligosaccharide compounds.

[0189] Suitably the composition comprises from 50 to 100 wt% oligosaccharide compounds, suitably from 55 to 95 wt%, or from 60 to 85 wt% oligosaccharide compounds.

[0190] In some embodiments, the composition is in the form of a syrup. The syrup suitably comprises at least 50 wt% of oligosaccharide compounds, at least 55 wt% of oligosaccharide compounds, or at least 60 wt% of oligosaccharide compounds. Suitably the syrup comprises from 50 to 75 wt% of oligosaccharide compounds, suitably from 55 to 70 wt% or from 60 to 70 wt% oligosaccharide compounds.

[0191] The syrup may comprise a significant amount of monosaccharides, for example glucose and / or galactose. The syrup may comprise from 15 to 30 wt% monosaccharides, suitably from 20 to 28 wt% monosaccharides or from 21 to 25 wt% monosaccharides, for example glucose and / or galactose.

[0192] The syrup suitably comprises from 20 to 30 wt% water, suitably from 22 to 28 wt% water.

[0193] The syrup may also contain lactose, for example 4 to 14 wt% lactose.

[0194] In some embodiments, the composition is in the form of a powder. The powder suitably comprises at least 60 wt% of oligosaccharide compounds, suitably at least 70 wt% or at least 75 wt% of oligosaccharide compounds. Suitably the powder comprises from 60 to 100 wt% of oligosaccharide compounds, suitably from 70 to 95 wt% or from 75 to 90 wt% oligosaccharide compounds.

[0195] The powder suitably comprises a reduced amount of monosaccharides, for example glucose and / or galactose, compared to the syrup discussed above. The powder may comprise from 1 to 10 wt% monosaccharides, suitably from 2 to 8 wt% monosaccharides or from 3 to 7 wt% monosaccharides, suitably approximately 5 wt%, for example of glucose and / or galactose.

[0196] The powder suitably comprises from 1 to 10 wt% water, suitably from 3 to 6 wt% water.

[0197] The composition of this first aspect may have been purified to remove monosaccharides and optionally disaccharides from the composition.

[0198] The composition of this first aspect may have been fractionated to separate the oligosaccharide components of the composition according to their molecular weight, for example to remove disaccharides from the composition or to isolate trisaccharides from the other oligosaccharide components. This may be carried out by any suitable method known in the art, for example high- performance liquid chromatography. The composition produced by such a fractionation may be referred to as an oligosaccharide fraction or a GOS fraction.

[0199] In such embodiments, the composition (or oligosaccharide fraction) suitably comprises at least 70 wt% of trisaccharides, tetrasaccharides and higher oligosaccharides, suitably at least 80 wt% or at least 90 wt%. Such higher oligosaccharides have a degree of polymerisation of 5 and above. Suitably the composition comprises at least 95 wt% of trisaccharides, tetrasaccharides and higher oligosaccharides. Suitably the composition consists or consists essentially of trisaccharides, tetrasaccharides and higher oligosaccharides.

[0200] In such embodiments, the composition suitably comprises from 40 to 70 wt% of trisaccharides, suitably from 45 to 70 wt% trisaccharides or from 50 to 70 wt% trisaccharides. Suitably the oligosaccharide compounds comprise from 15 to 50 wt% of tetrasaccharides, suitably from 15 to 40 wt% tetrasaccharides or from 20 to 40 wt% tetrasaccharides.

[0201] Suitably the oligosaccharide compounds comprise from 5 to 25 wt% of higher oligosaccharides, suitably from 5 to 20 wt% higher oligosaccharides or from 10 to 20 wt% higher oligosaccharides.

[0202] Suitably the composition comprises from 40 to 70 wt% trisaccharides, from 15 to 40 wt% tetrasaccharides and 5 to 25 wt% of higher oligosaccharides, based on the total weight of the composition. Suitably the composition comprises from 50 to 70 wt% trisaccharides, from 20 to 40 wt% tetrasaccharides and from 10 to 20 wt% higher oligosaccharides, based on the total weight of the composition.

[0203] In such embodiments the composition (or oligosaccharide fraction) suitably comprises the components (a), (b) and (c) as described above in the following amounts:

[0204] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0205] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0206] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc, based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xband Xcare each independently selected from monosaccharides.

[0207] Suitably the composition (or oligosaccharide fraction) comprises the components (a), (b) and (c) as described above in the following amounts:

[0208] (a) at least 10 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0209] (b) at least 5 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0210] (c) at least 7 wt% Gal-(p1-3)-Gal-(p1-2)-Xc.

[0211] The composition may comprise components (d) and / or component (e) as described above.

[0212] The composition suitably comprises said components in the ratios discussed above.

[0213] In some embodiments, the composition of this first aspect is a trisaccharide and tetrasaccharide fractionated product (which may be referred to as a DP3 / DP4 fraction). In such embodiments, the composition (or DP3 / DP4 fraction) suitably comprises at least 70 wt% of trisaccharides and tetrasaccharides, suitably at least 80 wt% or at least 90 wt%. Suitably the composition consists or consists essentially of trisaccharides and tetrasaccharides.

[0214] In such embodiments, the composition suitably comprises from 50 to 80 wt% of trisaccharides, suitably from 55 to 75 wt% trisaccharides or from 60 to 75 wt% trisaccharides.

[0215] Suitably the oligosaccharide compounds comprise from 20 to 50 wt% of tetrasaccharides, suitably from 25 to 45 wt% tetrasaccharides or from 25 to 40 wt% tetrasaccharides.

[0216] Suitably the composition comprises from 50 to 80 wt% trisaccharides and from 20 to 50 wt% tetrasaccharides, based on the total weight of the composition. Suitably the composition comprises from 60 to 75 wt% trisaccharides and from 25 to 40 wt% tetrasaccharides, based on the total weight of the composition.

[0217] In such embodiments the composition (or oligosaccharide fraction) suitably comprises the components (a), (b) and (c) as described above in the following amounts:

[0218] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0219] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0220] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc, based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xband Xcare each independently selected from monosaccharides.

[0221] Suitably the composition (or oligosaccharide fraction) comprises the components (a), (b) and (c) as described above in the following amounts:

[0222] (a) at least 10 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0223] (b) at least 5 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0224] (c) at least 7 wt% Gal-(p1-3)-Gal-(p1-2)-Xc.

[0225] The composition may comprise components (d) and / or component (e) as described above.

[0226] The composition suitably comprises said components in the ratios discussed above.

[0227] In some embodiments, the composition of this first aspect is a trisaccharide fractionated product (which may be referred to as a DP3 fraction). Such a trisaccharide fractionated product may be obtained by the known fractionation methods referred to above. Such a composition suitably comprises at least 70 wt% of trisaccharides, suitably at least 80 wt% or at least 90 wt%. Suitably the composition comprises at least 95 wt% of trisaccharides.

[0228] In such embodiments the composition (or oligosaccharide fraction) suitably comprises the components (a), (b) and (c) as described above in the following amounts:

[0229] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0230] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0231] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc, based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xband Xcare each independently selected from saccharides.

[0232] Suitably the composition (or oligosaccharide fraction) comprises the components (a), (b) and (c) as described above in the following amounts:

[0233] (a) at least 10 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0234] (b) at least 5 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0235] (c) at least 7 wt% Gal-(p1-3)-Gal-(p1-2)-Xc.

[0236] The composition may comprise component (e) as described above.

[0237] The composition suitably comprises said components in the ratios discussed above.

[0238] The composition of this first aspect may be for use as, and incorporated into, a food supplement product for ingestion by a consumer. Such a product may be selected from the group consisting of dairy products (for example, liquid milk, dried milk powder such as whole milk powder, skimmed milk powder, fat filled milk powders, whey powders, infant formula, ice cream, yoghurt, cheese, fermented dairy products), beverages, sports drinks, infant foods, cereals, bread, biscuits, confectionary, cakes, food supplements, dietary supplements, medical food / nutrition, food for specific medical purposes, animal feeds, poultry feeds or indeed any other food or beverage.

[0239] The composition of this first aspect may be incorporated into a synbiotic composition. Such a synbiotic composition is suitably a mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host, i.e. a probiotic and a prebiotic. The composition of this first aspect may be, for uses as, and in the form of, a pharmaceutical or nutraceutical composition comprising at least one carrier, excipient, or diluent.

[0240] Suitable further components of pharmaceutical or nutraceutical compositions and methods of preparing such pharmaceutical or nutraceutical compositions are known in the art.

[0241] The composition may be administered in a single dose or in multiple doses. A suitable frequency of administration may be at least once per day, every other day, once per week, once every two, three, or four weeks, once every month, two months, or once every three to six months. The composition may be administered over a period of at least a week, at least a month, at least three to six months, at least one, two, three, four, or five years, or over the course of the disease, or the lifetime of the subject.

[0242] The composition may be administered at a dosage of 2-4g per day. The composition may be administered at a dosage of about 2.75 or about 2.8g per day.

[0243] It will be apparent to the skilled addressee that the administration of the composition will be optimised during clinical trials.

[0244] Compositions of the invention can be formulated into pharmaceutical compositions by combination with appropriate pharmaceutically acceptable carriers, pharmaceutically acceptable diluents, or pharmaceutically acceptable excipients, and can be formulated into preparations in solid, semi-solid, or liquid forms, such as tablets, capsules, powders, granules and solutions.

[0245] Pharmaceutically acceptable carriers, excipients, or diluents may include, for example: water, saline, dextrose, maltodextrin, glycerol, ethanol, a salt, e.g., NaCI, MgCh, KCI, MgSC , etc.; a buffering agent, e.g., a phosphate buffer, a citrate buffer, a Tris buffer, N-(2- Hydroxyethyl)piperazine-N'-(2- ethanesulfonic acid) (HEPES), 2-(N- Morpholino)ethanesulfonic acid (MES), 2-(N- Morpholino)ethanesulfonic acid sodium salt (MES), 3-(N-Morpholino)propanesulfonic acid (MOPS), N-tris[Hydroxymethyl]methyl-3- aminopropanesulfonic acid (TAPS), etc.; a solubilizing agent; a detergent, e.g., a non-ionic detergent such as Tween-20, etc.; glycerol; and the like.

[0246] Pharmaceutically acceptable carriers, excipients and diluents are nontoxic to recipients at the dosages and concentrations employed, and can for example include buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid, glutathione, cysteine, methionine and citric acid; preservatives (such as ethanol, benzyl alcohol, phenol, m-cresol, p-chlor- m-cresol, methyl or propyl parabens, benzalkonium chloride, or combinations thereof); amino acids such as arginine, glycine, ornithine, lysine, histidine, glutamic acid, aspartic acid, isoleucine, leucine, alanine, phenylalanine, tyrosine, tryptophan, methionine, serine, proline and valine, and combinations thereof; monosaccharides, disaccharides and other carbohydrates; low molecular weight (less than about 10 residues) polypeptides; proteins, such as gelatin or serum albumin; chelating agents such as EDTA; sugars such as trehalose, sucrose, lactose, glucose, mannose, maltose, galactose, fructose, sorbose, raffinose, glucosamine, N-methylglucosamine, galactosamine, and neuraminic acid; and / or non-ionic surfactants such as Tween, Brij Pluronics, Triton-X, or polyethylene glycol (PEG).

[0247] For oral preparations, the composition of the invention may include appropriate additives to make tablets, powders, granules or capsules, for example, with 30 conventional additives, such as lactose, mannitol, corn starch or potato starch; with binders, such as crystalline cellulose, cellulose derivatives, acacia, corn starch or gelatins; with disintegrators, such as corn starch, potato starch or sodium carboxymethylcellulose; with lubricants, such as talc or magnesium stearate; and if desired, with diluents, buffering agents, moistening agents, preservatives and flavoring agents.

[0248] The pharmaceutical composition can be in a liquid form, a lyophilized form or a liquid form reconstituted from a lyophilized form, wherein the lyophilized preparation is to be reconstituted with a sterile solution prior to administration. The standard procedure for reconstituting a lyophilized composition is to add back a volume of pure water (typically equivalent to the volume removed during lyophilization).

[0249] A tonicity agent can be included in the formulation to modulate the tonicity of the formulation. Exemplary tonicity agents include sodium chloride, potassium chloride, glycerin and any component from the group of amino acids, sugars as well as combinations thereof. In some embodiments, the aqueous formulation is isotonic, although hypertonic or hypotonic solutions can be suitable. The term "isotonic" denotes a solution having the same tonicity as some other solution with which it is compared, such as a physiological salt solution or serum.

[0250] The composition may modulate the abundance of a bacterial genus present in the gut. In some embodiments, the composition modulates the abundance of a bacterial genus present in one or both of the small intestine or large intestine. In some embodiments, the composition modulates the abundance of a bacterial genus predominant in the small intestine selected from the genera Achromobacter, Agrobacterium, Blautia, Burkholderia, Coprococcus, Cryocola, Enterococcus, Eubacterium, Holdemania, Lactococcus, Mycobacterium, Pseudoramibacter, Ralstonia, Sphingomonas, Streptococcus, Turicibacter, Bifidobacterium and Lactobacillus. In some embodiments, the composition modulates the abundance of bacterial genera such as Bifidobacterium and Lactobacillus predominant in the large intestine.

[0251] According to a second aspect of the present invention, there is provided a method of preparing a composition comprising oligosaccharide compounds according to the first aspect, the method comprising the steps of:

[0252] (i) providing a source of saccharide compounds; (ii) treating the source of saccharide compounds with one or more galactosidase enzyme to at least partially convert the source of saccharide compounds to the oligosaccharide compounds.

[0253] Suitably the steps of the method of this second aspect are carried out in the order step (i) followed by step (ii).

[0254] Suitably the source of saccharide compounds comprises lactose, lactulose or epilactose. Suitably the source of saccharide compounds comprises lactose. The source of saccharide may be lactose, for example a lactose syrup which may be derived from cow’s milk. The lactose may be heat treated.

[0255] In some embodiments, no further saccharides, such as monosaccharides or disaccharides are added to the source of saccharide. In such embodiments, the method produces galactooligosaccharide compounds.

[0256] In some embodiments, the source of saccharide compounds comprises at least one additional saccharide. Suitably the at least one additional saccharide provides the oligosaccharide compounds with an alternative terminal monosaccharide unit, as discussed above. Suitably the at least one additional saccharide is a source of such a monosaccharide unit. The at least one additional saccharide which is a source of such a monosaccharide unit may be a monosaccharide or may be a higher sugar, such as a disaccharide. The at least one additional saccharide may be a source of a monosaccharide selected from glucose (Glc), fucose (Fuc), arabinose (Ara), xylose (Xyl), rhamnose (Rha), mannose (Man), galactose (Gal), ribose (Rib), lyxose (Lyx), allose (All), altrose (Alt), gulose (Gul), idose (Ido), talose (Tai), psicose (Psi), fructose (Fru), sorbose (Sor), tagatose (Tag), galactosamine (GalN), glucosamine (GlcN) and N-Acetylglucosamine (GIcNAc) or a mixture thereof. The at least one additional saccharide may be one or more of the monosaccharides listed above.

[0257] In such embodiments, the method produces oligosaccharides having one or more of the above monosaccharides as the terminal sugar unit.

[0258] In some embodiments, the at least one additional saccharide may be selected from Fucose, Arabinose, Xylose, Rhamnose, Mannose or mixtures thereof. The source of saccharides may comprise lactose and one or more sources of said monosaccharides. In such embodiments, the method produces oligosaccharides having as a terminal sugar unit selected from Glc, Fuc, Ara, Xyl, Rha and Man, or mixtures thereof.

[0259] Step (ii) of the method involves treating the source of saccharide compounds with at least one galactosidase enzyme. The galactosidase enzyme may be an alpha- or beta-galactosidase enzyme, depending on whether alpha or beta linkages between the saccharide units of the oligosaccharide compounds is required. Suitably the enzyme exhibits galactosyltransferase (transgalactosidic) activity and forms alpha- or beta- linkages between sugar units in the source of saccharide compounds. This results in the synthesis of oligosaccharide compounds with two or more galactose units derived from lactose. Suitably step (ii) is carried out until conversion of the source of saccharides to the oligosaccharide compounds is complete.

[0260] Step (ii) may involve treating the source of saccharide compounds with one or more additional enzymes which are not galactosidase enzymes.

[0261] Suitably the method comprises a step (iii) of separating the galactosidase enzyme from the composition comprising oligosaccharide compounds. Step (iii) may involve removing the enzyme by filtration, for example by nanofiltration.

[0262] The composition comprising oligosaccharide compounds produced in step (iii) may be heat treated.

[0263] In some embodiments, the composition is evaporated to reduce the water content to provide the final composition comprising oligosaccharide compounds as a syrup, as discussed above in relation to the first aspect.

[0264] In some embodiments, glucose is removed from the composition produced by step (iii) before evaporation. This suitably lowers the glucose content of the composition from 20-30 wt% to below 10 wt%, suitably approximately 5 wt% or lower. The water content of the composition is then reduced by evaporation and the product dried to provide the final composition comprising oligosaccharide compounds as a powder, as discussed above in relation to the first aspect.

[0265] It will also be appreciated that a person skilled in the relevant art could produce a composition comprising oligosaccharide compounds according to the first aspect, i.e. containing the specified amounts of particular oligosaccharide compounds, by combining said oligosaccharides obtained and isolated from different sources in the required amounts.

[0266] The invention will now be described with reference to the following numbered clauses:

[0267] A1 . A composition comprising an oligosaccharide compound(s) for use in

[0268] (i) the prevention, amelioration and / or treatment of gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions;

[0269] (ii) the reduction of plasma l-FABP during and / or after athletic activity in extreme environmental conditions; and / or

[0270] (iii) the increase of salivary immunoglobulin A (slgA) during and / or after athletic activity in extreme environmental conditions; wherein the oligosaccharide compound(s) comprise: (a) Gal-(p1-3)-Gal-(p1-4)-Xa; wherein, when the composition is used, the composition is provided to comprise:

[0271] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0272] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0273] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc; and optionally (d) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; and / or optionally (e) at least 5 wt% Gal-(p1-4)-Gal-(p1-4)-Xe; based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xb, Xc, Xdand Xeare each independently selected from monosaccharides.

[0274] A2. A composition comprising an oligosaccharide compound(s) for use in

[0275] (i) the prevention, amelioration and / or treatment of gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions;

[0276] (ii) the reduction of plasma l-FABP during and / or after athletic activity in extreme environmental conditions; and / or

[0277] (iii) the increase of salivary immunoglobulin A (slgA) during and / or after athletic activity in extreme environmental conditions; wherein the oligosaccharide compound(s) comprise:

[0278] (b) Gal-(p1-3)-Gal-(p1-3)-Xb; wherein, when the composition is used, the composition is provided to comprise:

[0279] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0280] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0281] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc; and optionally (d) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; and / or optionally (e) at least 5 wt% Gal-(p1-4)-Gal-(p1-4)-Xe; based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xb, Xc, Xdand Xeare each independently selected from monosaccharides.

[0282] A3. A composition comprising an oligosaccharide compound(s) for use in

[0283] (i) the prevention, amelioration and / or treatment of gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions;

[0284] (ii) the reduction of plasma l-FABP during and / or after athletic activity in extreme environmental conditions; and / or

[0285] (iii) the increase of salivary immunoglobulin A (slgA) during and / or after athletic activity in extreme environmental conditions; wherein the oligosaccharide compound(s) comprise:

[0286] (c) Gal-(p1-3)-Gal-(p1-2)-Xc; wherein, when the composition is used, the composition is provided to comprise:

[0287] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0288] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0289] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc; and optionally (d) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; and / or optionally (e) at least 5 wt% Gal-(p1-4)-Gal-(p1-4)-Xe; based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xb, Xc, Xdand Xeare each independently selected from monosaccharides. A4. A composition comprising an oligosaccharide compound(s) for use in

[0290] (i) the prevention, amelioration and / or treatment of gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions;

[0291] (ii) the reduction of plasma l-FABP during and / or after athletic activity in extreme environmental conditions; and / or

[0292] (iii) the increase of salivary immunoglobulin A (slgA) during and / or after athletic activity in extreme environmental conditions; wherein the oligosaccharide compound(s) comprise:

[0293] (d) Gal-(|31 -3)-Gal-(|31 -3)-Gal-(p1 -4)-Xd; wherein, when the composition is used, the composition is provided to comprise:

[0294] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0295] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0296] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc; and

[0297] (d) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; and / or optionally (e) at least 5 wt% Gal-(p1-4)-Gal-(p1-4)-Xe; based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xb, Xc, Xdand Xeare each independently selected from monosaccharides.

[0298] A5. A composition comprising an oligosaccharide compound(s) for use in

[0299] (i) the prevention, amelioration and / or treatment of gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions;

[0300] (ii) the reduction of plasma l-FABP during and / or after athletic activity in extreme environmental conditions; and / or (iii) the increase of salivary immunoglobulin A (slgA) during and / or after athletic activity in extreme environmental conditions; wherein the oligosaccharide compound(s) comprise:

[0301] (e) Gal-(p1-4)-Gal-(p1-4)-Xe; wherein, when the composition is used, the composition is provided to comprise:

[0302] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0303] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0304] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc; and optionally (d) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; and

[0305] (e) at least 5 wt% Gal-(p1-4)-Gal-(p1-4)-Xe; based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xb, Xc, Xdand Xeare each independently selected from monosaccharides.

[0306] A6. A composition comprising an oligosaccharide compound(s) for use in

[0307] (i) the prevention, amelioration and / or treatment of gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions;

[0308] (ii) the reduction of plasma l-FABP during and / or after athletic activity in extreme environmental conditions; and / or

[0309] (iii) the increase of salivary immunoglobulin A (slgA) during and / or after athletic activity in extreme environmental conditions; wherein the oligosaccharide compound(s) comprise:

[0310] (a) Gal-(p1-3)-Gal-(p1-4)-Xa; and

[0311] (b) Gal-(p1-3)-Gal-(p1-3)-Xb; wherein, when the composition is used, the composition is provided to comprise: (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0312] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0313] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc; and optionally (d) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; and / or optionally (e) at least 5 wt% Gal-(p1-4)-Gal-(p1-4)-Xe; based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xb, Xc, Xdand Xeare each independently selected from monosaccharides.

[0314] A7. A composition comprising an oligosaccharide compound(s) for use in

[0315] (i) the prevention, amelioration and / or treatment of gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions;

[0316] (ii) the reduction of plasma l-FABP during and / or after athletic activity in extreme environmental conditions; and / or

[0317] (iii) the increase of salivary immunoglobulin A (slgA) during and / or after athletic activity in extreme environmental conditions; wherein the oligosaccharide compound(s) comprise:

[0318] (a) Gal-(p1-3)-Gal-(p1-4)-Xa; and

[0319] (c) Gal-(p1-3)-Gal-(p1-2)-Xc; wherein, when the composition is used, the composition is provided to comprise:

[0320] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0321] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0322] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc; and optionally (d) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; and / or optionally (e) at least 5 wt% Gal-(p1-4)-Gal-(p1-4)-Xe; based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xb, Xc, Xdand Xeare each independently selected from monosaccharides.

[0323] A8. A composition comprising an oligosaccharide compound(s) for use in

[0324] (i) the prevention, amelioration and / or treatment of gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions;

[0325] (ii) the reduction of plasma l-FABP during and / or after athletic activity in extreme environmental conditions; and / or

[0326] (iii) the increase of salivary immunoglobulin A (slgA) during and / or after athletic activity in extreme environmental conditions; wherein the oligosaccharide compound(s) comprise:

[0327] (a) Gal-(p1-3)-Gal-(p1-4)-Xa; and

[0328] (d) Gal-(|31 -3)-Gal-(|31 -3)-Gal-(p1 -4)-Xd; wherein, when the composition is used, the composition is provided to comprise:

[0329] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0330] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0331] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc; and

[0332] (d) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; and / or optionally (e) at least 5 wt% Gal-(p1-4)-Gal-(p1-4)-Xe; based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xb, Xc, Xdand Xeare each independently selected from monosaccharides. A9. A composition comprising an oligosaccharide compound(s) for use in

[0333] (i) the prevention, amelioration and / or treatment of gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions;

[0334] (ii) the reduction of plasma l-FABP during and / or after athletic activity in extreme environmental conditions; and / or

[0335] (iii) the increase of salivary immunoglobulin A (slgA) during and / or after athletic activity in extreme environmental conditions; wherein the oligosaccharide compound(s) comprise:

[0336] (a) Gal-(p1-3)-Gal-(p1-4)-Xa; and

[0337] (e) Gal-(p1-4)-Gal-(p1-4)-Xe; wherein, when the composition is used, the composition is provided to comprise:

[0338] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0339] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0340] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc; and optionally (d) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; and

[0341] (e) at least 5 wt% Gal-(p1-4)-Gal-(p1-4)-Xe; based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xb, Xc, Xdand Xeare each independently selected from monosaccharides.

[0342] A10. A composition comprising an oligosaccharide compound(s) for use in

[0343] (i) the prevention, amelioration and / or treatment of gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions; (ii) the reduction of plasma l-FABP during and / or after athletic activity in extreme environmental conditions; and / or

[0344] (iii) the increase of salivary immunoglobulin A (slgA) during and / or after athletic activity in extreme environmental conditions; wherein the oligosaccharide compound(s) comprise:

[0345] (b) Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0346] (c) Gal-(p1-3)-Gal-(p1-2)-Xc; wherein, when the composition is used, the composition is provided to comprise:

[0347] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0348] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0349] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc; and optionally (d) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; and / or optionally (e) at least 5 wt% Gal-(p1-4)-Gal-(p1-4)-Xe; based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xb, Xc, Xdand Xeare each independently selected from monosaccharides.

[0350] A11 . A composition comprising an oligosaccharide compound(s) for use in

[0351] (i) the prevention, amelioration and / or treatment of gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions;

[0352] (ii) the reduction of plasma l-FABP during and / or after athletic activity in extreme environmental conditions; and / or

[0353] (iii) the increase of salivary immunoglobulin A (slgA) during and / or after athletic activity in extreme environmental conditions; wherein the oligosaccharide compound(s) comprise: (b) Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0354] (d) Gal-(|31 -3)-Gal-(|31 -3)-Gal-(p1 -4)-Xd; wherein, when the composition is used, the composition is provided to comprise:

[0355] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0356] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0357] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc; and

[0358] (d) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; and / or optionally (e) at least 5 wt% Gal-(p1-4)-Gal-(p1-4)-Xe; based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xb, Xc, Xdand Xeare each independently selected from monosaccharides.

[0359] A12. A composition comprising an oligosaccharide compound(s) for use in

[0360] (i) the prevention, amelioration and / or treatment of gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions;

[0361] (ii) the reduction of plasma l-FABP during and / or after athletic activity in extreme environmental conditions; and / or

[0362] (iii) the increase of salivary immunoglobulin A (slgA) during and / or after athletic activity in extreme environmental conditions; wherein the oligosaccharide compound(s) comprise:

[0363] (b) Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0364] (e) Gal-(p1-4)-Gal-(p1-4)-Xe; wherein, when the composition is used, the composition is provided to comprise:

[0365] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa; (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0366] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc; and optionally (d) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; and

[0367] (e) at least 5 wt% Gal-(p1-4)-Gal-(p1-4)-Xe; based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xb, Xc, Xdand Xeare each independently selected from monosaccharides.

[0368] A13. A composition comprising an oligosaccharide compound(s) for use in

[0369] (i) the prevention, amelioration and / or treatment of gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions;

[0370] (ii) the reduction of plasma l-FABP during and / or after athletic activity in extreme environmental conditions; and / or

[0371] (iii) the increase of salivary immunoglobulin A (slgA) during and / or after athletic activity in extreme environmental conditions; wherein the oligosaccharide compound(s) comprise:

[0372] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc; and

[0373] (d) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; wherein, when the composition is used, the composition is provided to comprise:

[0374] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0375] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0376] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc; and optionally (d) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; and

[0377] (e) at least 5 wt% Gal-(p1-4)-Gal-(p1-4)-Xe; based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xb, Xc, Xdand Xeare each independently selected from monosaccharides.

[0378] A14. A composition comprising an oligosaccharide compound(s) for use in

[0379] (i) the prevention, amelioration and / or treatment of gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions;

[0380] (ii) the reduction of plasma l-FABP during and / or after athletic activity in extreme environmental conditions; and / or

[0381] (iii) the increase of salivary immunoglobulin A (slgA) during and / or after athletic activity in extreme environmental conditions; wherein the oligosaccharide compound(s) comprise:

[0382] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc; and

[0383] (e) Gal-(p1-4)-Gal-(p1-4)-Xe; wherein, when the composition is used, the composition is provided to comprise:

[0384] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0385] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0386] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc; and optionally (d) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; and

[0387] (e) at least 5 wt% Gal-(p1-4)-Gal-(p1-4)-Xe; based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xb, Xc, Xdand Xeare each independently selected from monosaccharides.

[0388] A15. A composition comprising an oligosaccharide compound(s) for use in (i) the prevention, amelioration and / or treatment of gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions;

[0389] (ii) the reduction of plasma l-FABP during and / or after athletic activity in extreme environmental conditions; and / or

[0390] (iii) the increase of salivary immunoglobulin A (slgA) during and / or after athletic activity in extreme environmental conditions; wherein the oligosaccharide compound(s) comprise:

[0391] (d) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; and

[0392] (e) Gal-(p1-4)-Gal-(p1-4)-Xe; wherein, when the composition is used, the composition is provided to comprise:

[0393] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0394] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0395] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc; and optionally (d) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; and

[0396] (e) at least 5 wt% Gal-(p1-4)-Gal-(p1-4)-Xe; based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xb, Xc, Xdand Xeare each independently selected from monosaccharides.

[0397] A16. A composition comprising an oligosaccharide compound(s) for use in

[0398] (i) the prevention, amelioration and / or treatment of gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions;

[0399] (ii) the reduction of plasma l-FABP during and / or after athletic activity in extreme environmental conditions; and / or (iii) the increase of salivary immunoglobulin A (slgA) during and / or after athletic activity in extreme environmental conditions; wherein the oligosaccharide compound(s) comprise:

[0400] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0401] (b) Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0402] (d) Gal-(|31 -3)-Gal-(|31 -3)-Gal-(p1 -4)-Xd; wherein, when the composition is used, the composition is provided to comprise:

[0403] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0404] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0405] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc; and

[0406] (d) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; and / or optionally (e) at least 5 wt% Gal-(p1-4)-Gal-(p1-4)-Xe; based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xb, Xc, Xdand Xeare each independently selected from monosaccharides.

[0407] A17. A composition comprising an oligosaccharide compound(s) for use in

[0408] (i) the prevention, amelioration and / or treatment of gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions;

[0409] (ii) the reduction of plasma l-FABP during and / or after athletic activity in extreme environmental conditions; and / or

[0410] (iii) the increase of salivary immunoglobulin A (slgA) during and / or after athletic activity in extreme environmental conditions; wherein the oligosaccharide compound(s) comprise:

[0411] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa; (b) Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0412] (e) at least 5 wt% Gal-(p1-4)-Gal-(p1-4)-Xe; wherein, when the composition is used, the composition is provided to comprise:

[0413] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0414] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0415] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc; and

[0416] (d) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; and / or optionally (e) at least 5 wt% Gal-(p1-4)-Gal-(p1-4)-Xe; based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xb, Xc, Xdand Xeare each independently selected from monosaccharides.

[0417] A18. A composition comprising an oligosaccharide compound(s) for use in

[0418] (i) the prevention, amelioration and / or treatment of gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions;

[0419] (ii) the reduction of plasma l-FABP during and / or after athletic activity in extreme environmental conditions; and / or

[0420] (iii) the increase of salivary immunoglobulin A (slgA) during and / or after athletic activity in extreme environmental conditions; wherein the oligosaccharide compound(s) comprise:

[0421] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0422] (c) Gal-(p1-3)-Gal-(p1-2)-Xc; and

[0423] (d) Gal-(|31 -3)-Gal-(|31 -3)-Gal-(p1 -4)-Xd; wherein, when the composition is used, the composition is provided to comprise: (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0424] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0425] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc; and

[0426] (d) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; and / or optionally (e) at least 5 wt% Gal-(p1-4)-Gal-(p1-4)-Xe; based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xb, Xc, Xdand Xeare each independently selected from monosaccharides.

[0427] A19. A composition comprising an oligosaccharide compound(s) for use in

[0428] (i) the prevention, amelioration and / or treatment of gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions;

[0429] (ii) the reduction of plasma l-FABP during and / or after athletic activity in extreme environmental conditions; and / or

[0430] (iii) the increase of salivary immunoglobulin A (slgA) during and / or after athletic activity in extreme environmental conditions; wherein the oligosaccharide compound(s) comprise:

[0431] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0432] (c) Gal-(p1-3)-Gal-(p1-2)-Xc; and

[0433] (e) at least 5 wt% Gal-(p1-4)-Gal-(p1-4)-Xe; wherein, when the composition is used, the composition is provided to comprise:

[0434] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0435] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0436] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc; and (d) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; and / or optionally (e) at least 5 wt% Gal-(p1-4)-Gal-(p1-4)-Xe; based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xb, Xc, Xdand Xeare each independently selected from monosaccharides.

[0437] A20. A composition comprising an oligosaccharide compound(s) for use in

[0438] (i) the prevention, amelioration and / or treatment of gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions;

[0439] (ii) the reduction of plasma l-FABP during and / or after athletic activity in extreme environmental conditions; and / or

[0440] (iii) the increase of salivary immunoglobulin A (slgA) during and / or after athletic activity in extreme environmental conditions; wherein the oligosaccharide compound(s) comprise:

[0441] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0442] (d) Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; and

[0443] (d) Gal-(|31 -3)-Gal-(|31 -3)-Gal-(p1 -4)-Xd; wherein, when the composition is used, the composition is provided to comprise:

[0444] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0445] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0446] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc; and

[0447] (d) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; and / or optionally (e) at least 5 wt% Gal-(p1-4)-Gal-(p1-4)-Xe; based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xb, Xc, Xdand Xeare each independently selected from monosaccharides.

[0448] A21 . A composition comprising an oligosaccharide compound(s) for use in

[0449] (i) the prevention, amelioration and / or treatment of gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions;

[0450] (ii) the reduction of plasma l-FABP during and / or after athletic activity in extreme environmental conditions; and / or

[0451] (iii) the increase of salivary immunoglobulin A (slgA) during and / or after athletic activity in extreme environmental conditions; wherein the oligosaccharide compound(s) comprise:

[0452] (b) Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0453] (c) Gal-(p1-3)-Gal-(p1-2)-Xc; and

[0454] (d) Gal-(|31 -3)-Gal-(|31 -3)-Gal-(p1 -4)-Xd; wherein, when the composition is used, the composition is provided to comprise:

[0455] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0456] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0457] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc; and

[0458] (d) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; and / or optionally (e) at least 5 wt% Gal-(p1-4)-Gal-(p1-4)-Xe; based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xb, Xc, Xdand Xeare each independently selected from monosaccharides.

[0459] A22. A composition comprising an oligosaccharide compound(s) for use in (i) the prevention, amelioration and / or treatment of gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions;

[0460] (ii) the reduction of plasma l-FABP during and / or after athletic activity in extreme environmental conditions; and / or

[0461] (iii) the increase of salivary immunoglobulin A (slgA) during and / or after athletic activity in extreme environmental conditions; wherein the oligosaccharide compound(s) comprise:

[0462] (b) Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0463] (c) Gal-(p1-3)-Gal-(p1-2)-Xc; and

[0464] (e) Gal-(p1-4)-Gal-(p1-4)-Xe; wherein, when the composition is used, the composition is provided to comprise:

[0465] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0466] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0467] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc; and optionally (d) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; and

[0468] (e) at least 5 wt% Gal-(p1-4)-Gal-(p1-4)-Xe; based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xb, Xc, Xdand Xeare each independently selected from monosaccharides.

[0469] A23. A composition comprising an oligosaccharide compound(s) for use in

[0470] (i) the prevention, amelioration and / or treatment of gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions; (ii) the reduction of plasma l-FABP during and / or after athletic activity in extreme environmental conditions; and / or

[0471] (iii) the increase of salivary immunoglobulin A (slgA) during and / or after athletic activity in extreme environmental conditions; wherein the oligosaccharide compound(s) comprise:

[0472] (b) Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0473] (d) Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; and

[0474] (e) Gal-(p1-4)-Gal-(p1-4)-Xe; wherein, when the composition is used, the composition is provided to comprise:

[0475] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0476] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0477] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc; and

[0478] (d) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; and

[0479] (e) at least 5 wt% Gal-(p1-4)-Gal-(p1-4)-Xe; based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xb, Xc, Xdand Xeare each independently selected from monosaccharides.

[0480] A24. A composition comprising an oligosaccharide compound(s) for use in

[0481] (i) the prevention, amelioration and / or treatment of gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions;

[0482] (ii) the reduction of plasma l-FABP during and / or after athletic activity in extreme environmental conditions; and / or

[0483] (iii) the increase of salivary immunoglobulin A (slgA) during and / or after athletic activity in extreme environmental conditions; wherein the oligosaccharide compound(s) comprise:

[0484] (c) Gal-(p1-3)-Gal-(p1-2)-Xc; and

[0485] (d) Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; and

[0486] (e) Gal-(p1-4)-Gal-(p1-4)-Xe; wherein, when the composition is used, the composition is provided to comprise:

[0487] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0488] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0489] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc; and

[0490] (d) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; and

[0491] (e) at least 5 wt% Gal-(p1-4)-Gal-(p1-4)-Xe; based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xb, Xc, Xdand Xeare each independently selected from monosaccharides.

[0492] A25. A composition comprising an oligosaccharide compound(s) for use in

[0493] (i) the prevention, amelioration and / or treatment of gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions;

[0494] (ii) the reduction of plasma l-FABP during and / or after athletic activity in extreme environmental conditions; and / or

[0495] (iii) the increase of salivary immunoglobulin A (slgA) during and / or after athletic activity in extreme environmental conditions; wherein the oligosaccharide compound(s) comprise:

[0496] (a) Gal-(p1-3)-Gal-(p1-4)-Xa;

[0497] (b) Gal-(p1-3)-Gal-(p1-3)-Xb; and (d) Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; and

[0498] (e) Gal-(p1-4)-Gal-(p1-4)-Xe; wherein, when the composition is used, the composition is provided to comprise:

[0499] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0500] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0501] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc; and

[0502] (d) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; and

[0503] (e) at least 5 wt% Gal-(p1-4)-Gal-(p1-4)-Xe; based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xb, Xc, Xdand Xeare each independently selected from monosaccharides.

[0504] A26. A composition comprising an oligosaccharide compound(s) for use in

[0505] (i) the prevention, amelioration and / or treatment of gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions;

[0506] (ii) the reduction of plasma l-FABP during and / or after athletic activity in extreme environmental conditions; and / or

[0507] (iii) the increase of salivary immunoglobulin A (slgA) during and / or after athletic activity in extreme environmental conditions; wherein the oligosaccharide compound(s) comprise:

[0508] (a) Gal-(p1-3)-Gal-(p1-4)-Xa;

[0509] (c) Gal-(p1-3)-Gal-(p1-2)-Xc; and

[0510] (d) Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; and

[0511] (e) Gal-(p1-4)-Gal-(p1-4)-Xe; wherein, when the composition is used, the composition is provided to comprise:

[0512] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;

[0513] (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0514] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc; and

[0515] (d) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; and

[0516] (e) at least 5 wt% Gal-(p1-4)-Gal-(p1-4)-Xe; based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xb, Xc, Xdand Xeare each independently selected from monosaccharides.

[0517] A27. A composition comprising an oligosaccharide compound(s) for use in

[0518] (i) the prevention, amelioration and / or treatment of gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions;

[0519] (ii) the reduction of plasma l-FABP during and / or after athletic activity in extreme environmental conditions; and / or

[0520] (iii) the increase of salivary immunoglobulin A (slgA) during and / or after athletic activity in extreme environmental conditions; wherein the oligosaccharide compound(s) comprise:

[0521] (b) Gal-(p1-3)-Gal-(p1-3)-Xb;

[0522] (c) Gal-(p1-3)-Gal-(p1-2)-Xc; and

[0523] (d) Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; and

[0524] (e) Gal-(p1-4)-Gal-(p1-4)-Xe; wherein, when the composition is used, the composition is provided to comprise:

[0525] (a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa; (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and

[0526] (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc; and

[0527] (d) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd; and

[0528] (e) at least 5 wt% Gal-(p1-4)-Gal-(p1-4)-Xe; based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xb, Xc, Xdand Xeare each independently selected from monosaccharides.

[0529] The invention is described below, by way of example only, with reference to the accompanying figures in which:

[0530] Figure 1 is a graph illustrating the results of the butyrate analysis across three donors after being administered the oligosaccharide of the present invention alongside a comparative oligosaccharide.

[0531] Figure 2 is a bar chart showing the peak A plasma l-FABP during and following a Football Specific Intermittent Treadmill Protocol (FSITP) at day 0 to day 42. Data are presented as median ± SE. The asterisk (*) denotes a significant difference between groups (p<0.05).

[0532] Figure 3 is a bar chart showing the mean change from day 0 to day 42 in pre-post FSITP slgA secretion rate. slgA levels in the B-GOS group are shown in the left-hand bar and slgA levels for the placebo group are shown in the right-hand bar. Data are presented as mean ± SD. The asterisk (*) denotes a significant difference between groups (p<0.05).

[0533] Figure 4 is a bar chart showing the percentage change in total Gl symptom severity score during FSITP between day 0 and day 42. Data are presented as mean ± SD. The asterisk (*) denotes a significant difference between groups (p<0.05).

[0534] Examples

[0535] Example 1 - oligosaccharide syrup

[0536] A composition comprising oligosaccharide compounds according to the present invention, in the form of a syrup, was obtained by the following procedure. Lactose was rehydrated with potable water to give a working solution of between 35-65 wt% solids. The lactose solution was heat treated then cooled to 40-65°C. The pH of the solution was adjusted to pH 5.5-7.5. A beta-galactosidase enzyme was then added to the solution in a closed vessel and subsequently allowed to react with the lactose to catalyse the transfer of galactose molecules to produce oligosaccharide compounds. The progress of the reaction was monitored by measuring the generation of glucose. The reaction was allowed to proceed for between 8 and 26 hours. The reaction was then terminated by high heat treatment. The reaction mixture was cooled and filtered by carbon filtration to remove the enzyme. The mixture was then evaporated to reduce the water content to approximately 22-28 wt% to provide the product as a syrup.

[0537] Example 2 - oligosaccharide powder

[0538] A composition comprising oligosaccharide compounds according to the present invention, in the form of a powder, was obtained by a modification of the procedure described above. After removal of the enzyme, the mixture was further filtered to remove a significant portion of the glucose and other monosaccharides, reducing the monosaccharide content from around 23 wt% to around 5 wt%. The water content of the composition was then reduced by evaporation and the product dried to provide a powder having a water content to approximately 3-6 wt%.

[0539] Example 3 - fractionation

[0540] Isolation of the different fractions (DP2, DP3, DP4 or DP5) from a sample of Example 2 was performed using a 5 x 70 cm BioGel P2 column, using water as eluent. The column was operated with a flow speed of 40 to 100 mL / h at room temperature (21 °C). Depending on the run, 0.5, 0.75, 1.0, 1.5 or 2.0 mL of a 0.5 g / mL solution of Example 2 in ultrapure water was loaded. The column was loaded in total 15 times with this solution to obtain enough material of the low abundant fractions, i.e. DP5. After a void volume of around 725 mL, 5 mL fractions were collected. Analyses using thin layer chromatography (TLC) and HPAEC-PAD were carried out to ensure molecules with the same DP are pooled.

[0541] Pooled fractions were frozen and lyophilized. The dry material of all runs was combined and redissolved. After a second cycle of freezing and lyophilization, the dry material was stored at 4 °C for further analyses or experimentation.

[0542] Comparative Example 1

[0543] A commercially available composition comprising oligosaccharide compounds was obtained in powder form.

[0544] Oligosaccharide analysis

[0545] Samples of Example 2 of the present invention and Comparative Example 1 were analysed to determine their oligosaccharide content by the following procedure. Materials and Methods

[0546] Samples of dry powder of each of Example 2 and Comparative Example 1 were dissolved in water to provide solutions having a concentration of 40 g / l for analysis.

[0547] Gel permeation chromatography

[0548] An HPLC apparatus equipped with a Rezex RSO and a Rl detector and in-line desalting (for removal of salts and charged material like proteins) was used for the aqueous GPC separation of the components of the samples. The separation was performed at elevated temperature (80°C). The separation range of the Rezex RSO column is from DP1 (monosaccharide) up to about DP10. All samples were analysed undiluted (at 40 g / L). Before analysis, all sample solutions were treated at 100°C for ten minutes in order to remove any microbiological or enzymatic activity.

[0549] GOS fingerprinting

[0550] HPAEC-PAD (high performance anion exchange chromatography) equipped with a PA-1 column was used for separation of mono- and oligosaccharides of the different samples. Efforts were made to achieve a separation quality described in van Leeuwen et al., Carbohydrate Research 2016, 425, 48-58. A commercial maltooligosaccharide mixture and Comparative Example 1 were also injected for comparison of chromatograms with those reported by Van Leeuwen et al. Based on this, peak annotations were made for a number of peaks. The samples as used for GPC were 100-fold diluted with DMSO before injection.

[0551] Results

[0552] Gel permeation chromatography (GPC-RI)

[0553] Table 1 shows DP (degree of polymerisation) composition results for the samples using Rezex-RSO system, based on Rl calibration with glucose (values expressed as g / L in the samples). All material eluting in the >DP5 window was combined.

[0554] Table 1

[0555] The concentration information can be used to calculate the relative weight percentages of the different DP fractions of oligosaccharides contained in the samples, as shown in Table 1 , wherein DP=2 refers to disaccharides, DP=3 refers to trisaccharides etc. GOS fingerprinting

[0556] To identify the individual galactooligosaccharides in the sample (GOS fingerprinting) a gradient was developed giving comparable separation to that reported in van Leeuwen et al., Carbohydrate Research 2016, 425, 48-58. Peak annotations were made in the chromatograms of all GOS samples based on peak annotations made in van Leeuwen et al. for the oligosaccharide compounds. Retention windows of about 15 seconds were applied for peak annotation.

[0557] Table 2 shows information on HPAEC-PAD peak areas of all annotated peaks together with information on incubation conditions, sample concentration, dilution and injection volume as shown.

[0558] Table 2

[0559] The peak areas were assumed to approximately correspond to the amount of each oligosaccharide compound present in the composition. Where a particular oligosaccharide compound was not identified then “unknown” and a number is entered in the table. The identified compounds are either identified by name or by a number which corresponds to the number assigned to particular galactooligosaccharides in van Leeuwen et al., Carbohydrate Research 2016, 425, 48-58. A list of these galactooligosaccharides and their corresponding numbers is provided below.

[0560] The wt% shown in table 2 are based on the total composition i.e. the total sugars present in the composition and are not based on the total oligosaccharides. For instance, glucose, galactose and lactose are not considered to be oligosaccharides.

[0561] The oligosaccharide components (a)-(e) discussed above, wherein each X group is Glu, correspond to the following numbered entries in Table 2 above:

[0562] (a) D-Gal-(pi-3)-D-Gal-(|31-4)-D-Glu - 12

[0563] (b) D-Gal-(pi-3)-D-Gal-(pi-3)-D-Glu - 29

[0564] (c) D-Gal-(pi-3)-D-Gal-(pi-2)-D-Glu - 30

[0565] (d) D-Gal-(pi-3)-D-Gal-(pi-3)-D-Gal-(pi-4)-D-Glu - 31

[0566] (e) D-Gal-(pi-4)-D-Gal-(pi-4)-D-Glu - 11.

[0567] Prebiotic effects - butyrate production

[0568] Butyrate is produced by gut microbiota which convert acetate and / or lactate (along with other substrates) to butyrate. As butyrate can be a secondary metabolite, it is often produced during late stages of fermentation as butyrate can be directly produced by certain bacterial butyrate producers.

[0569] These experiments were aimed at assessing the difference in butyrate production of the compositions of the present invention alongside a comparative GOS composition to see if they were more effective as a prebiotic. The experiments used the following procedure. The compositions of Example 2 of the present invention, Comparative Example 1 and a control blank sample were subjected to dialysis using a 0.5 kDa membrane to provide 5 g / l samples which were then mixed with faecal matter obtained from three healthy human adult subjects (donors A, B and C). The mixtures were shaken under anaerobic conditions and monitored over a 48-hour period for colonic fermentation products including butyrate (with 6, 24 and 48 h collection points). The distribution of oligosaccharides in the mixtures was also monitored over this time period using the method described above in relation to Table 2. The results show that Example 2 was well fermented by all donors, mainly during the time period 0-24 hours and that butyrate production increased compared to the Comparative Example 1 and the control at the 6 and 48 hour time points. The results of the butyrate analysis are shown in Figure 1 . The results of the oligosaccharides analysis for the samples at the different time points are shown in Table 3. These results show that the oligosaccharides in the samples were actively consumed by the microbiota present in the faecal samples during the experiments.

[0570] To assess whether treatment effects on gut microbial activity were statistically significant, three two- sided T-tests were performed between Example 2 and the control, Comparative Example 1 and the control and Example 2 and Comparative Example 1 to obtain p-values. The Benjamini-Hochberg false discovery rate (FDR) was also used in this analysis. Differences between treatment effects were considered significant when the obtained p-value was smaller than a reference value. Table 4 below shows the differences in the averaged butyrate production for the compared samples over 48 hours and the asterisk denotes whether the difference was considered significant according to the analysis described above. These results show that the increase in butyrate production provided by

[0571] Example 2 during the time period 0-48 hours was statistically significant compared to the control and Comparative Example 1 .

[0572] Table 3

[0573]

[0574] Table 4

[0575] In summary, the present invention provides a composition comprising oligosaccharide compounds, for example galactooligosaccharide compounds, which includes: (a) at least 8 wt% Gal-(p1-3)-Gal- (p1-4)-Xa; (b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and (c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)- Xc, based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xband Xcare each independently selected from monosaccharides. These compositions contain relatively high amounts of the oligosaccharide compounds (a), (b) and (c) and a relatively high amount of p1-3 Gal-Gal linkages, compared to known oligosaccharide compositions. These particular features of the composition are believed to provide benefits to the gut health of a consumer, for example due to these compositions providing an increased production of butyrate in the gut of a consumer compared to known compositions.

[0576] Example 4

[0577] A study was carried out over 6 weeks administering a prebiotic galactooligosaccharide (GOS) supplement and investigating its effect on markers of gastrointestinal damage, permeability, inflammation and Gl symptoms in team sport athletes following a football specific treadmill protocol in the heat. The GOS used in this study had a composition according to the present invention.

[0578] Methods:

[0579] In a double-blind, randomised controlled trial, twenty-four male team sport athletes were randomised to receive 2.8 g / d of either Bimuno-galactooligosaccharide (B-GOS; n=12) or a maltodextrin placebo (PLA; n=12) for 6 weeks. The twenty-four recruits were physically active, non-smokers and regularly perform team-based activity (>3hrs of team sport activity per week). The study recruits were aged 18-45 years old. All participants were within a normal body mass index range (20-25 kg.m2). Participants were randomised to one of two groups (based on age, body mass, and training status) and consumed an intervention of:

[0580] B-GOS (Bimuno) (prebiotic, PRE) - 3.65 g / day (containing 2.8g of GOS) was consumed by participants throughout the 6-week intervention period (1 sachet provided am). This dose has been shown previously to be well tolerated by healthy individuals and is commercially available as Bimuno Galactooligosaccharide Powder.

[0581] Placebo (PLA)- maltodextrin - 3.65 g / day (1 sachet provided am). The placebo was identical to the prebiotic but contained the equivalent dose of maltodextrin powder to be consumed in the morning. Maltodextrin is a food grade carbohydrate but is not selectively fermented by the gut bacteria. It looks and tastes identical to GOS.

[0582] Both supplements were identical in appearance and taste and participants were instructed to mix the powder into a drink each morning.

[0583] Experimental visits

[0584] Pre- and post-intervention, each participant completed an experimental trial where they completed a simulated football match on a treadmill in 33°C.

[0585] Prior to each experimental visit the participants were allowed to follow their usual diet (for 48 hours prior) but recorded it in a food diary and then replicated this for each following experimental visit. No strenuous exercise in the 48 hours priorto visiting the laboratory, or alcohol and caffeine consumption 12 hours prior to testing was allowed. On the day of the experimental visits participants arrived at the laboratory in a fasted state where they were provided breakfast, water and supplement (prebiotic / placebo- visit 3 & 6 only).

[0586] Visit 1 comprised a briefing, consent, health screening and maximal oxygen uptake testing in the heat.

[0587] Speed Lactate Test

[0588] Participants completed an incremental treadmill run starting at 9 km h -1 , 1 % gradient with the speed increasing by 1 km h -1 every 3 minutes. At the end of each stage the participant stopped and a capillary blood sample was collected from the fingertip for the assessment of lactate. The test stopped once there had been an increase > 1 mmoL / l when compared to the previous stage. Heart rate and rating of perceived exertion was also measured at the end of each 3 minute stage.

[0589] Standard incremental treadmill test

[0590] Following a 15-minute rest participants completed a standard incremental treadmill test for the determination of VO2MAX and gas exchange threshold, this was performed at 33°C within the environmental chamber. The test involved participants completing an incremental treadmill run to fatigue starting at 9-10 km h -1 , 1 % gradient with the speed increasing by 1 km h -1 each minute until a speed of 18 km h -1 . After 1 min at 18 km h -1 , the treadmill gradient was increased by 1 % each minute until volitional fatigue. Heart rate was measured every minute, and respiratory variables were measured breath-by-breath and recorded every 30s through the use of a face mask and breath- by-breath analyser. Participants wore a Hans Rudolph face mask with an inserted pneumotach and flow sensor, which was connected to metabolic cart (Vyntus CPX, Vyaire Medical Inc, United Kingdom). Exhaled air was analysed to determine oxygen consumption (02), carbon dioxide production (CO2) and minute ventilation (VE). This was used to determine the gas exchange threshold (GET) (VE / VCO2) for each participant. VO2MAX was determined as an average of the two highest consecutive readings. Arterial oxygen saturation using pulse oximetry was measured continuously throughout the test.

[0591] Visit 2 - Familiarisation in the heat

[0592] Participants performed one half of the football specific intermittent treadmill protocol (FSITP) in the heat (33°C). Participants completed a health and medical questionnaire, had their height and weight measured and then completed a standardised incremental treadmill test for the assessment of maximal oxygen uptake.

[0593] Visit 3 & 6 - Experimental trials

[0594] Following the incremental treadmill test and determination of the lactate threshold and VO2max participants then underwent two visits separated by a 42-day supplementation period to complete a 90minute FSITP in the heat (33°C). Participants arrived 4 hours prior to the start of exercise following an overnight fast, where they were provided with a breakfast and water to maintain euhydration. A fasted venous blood sample using a vacutainer, saliva and a urine sample was collected prior to the breakfast, then 2 hours after breakfast, immediately pre, half-way through the FSITP, immediately post FSTIP and 60minutes post FSTIP. 20ml of blood was collected at each time-point for the assessment of systemic markers of gastrointestinal damage (l-FABP), permeability (LBP, Claudin- 3), inflammation (CRP, TNF-a, IL-6, IL-10) and Ammonia making a total of 100ml of blood per visit. All blood samples were centrifuged following manufacturer’s instructions to produce plasma before storage in -80°C freezer. A saliva sample was also collected pre, immediately post and 1-hour post for the assessment of IgA. Heart rate, arterial oxygen saturation, skin temperature and core temperature were continuously monitored throughout the exercise task. Subjective assessment of gastrointestinal discomfort, RPE (Rating of Perceived Exertion) and thermal discomfort were assessed throughout the FSITP. A battery of cognitive function tests were completed at baseline, half-time and full-time. The battery of tests took 15 min and consisted of the Visual Search test, the Stroop test, the Corsi blocks test and the RVIP test. All three batteries of cognitive tests were completed inside the environmental chamber.

[0595] Participants sat in the environmental chamber for 10 mins before starting the FSITP. The FSITP is made up of 2 x 45 min blocks of activity, separated by a 15 min rest period to simulate halftime. The entire protocol was completed on a motorised treadmill (h / p / cosmos Para Graphics, Nussdorf- Taunstein, Germany) at a 1 % gradient in order to simulate outdoor running. The treadmill speeds were individualised and determined by participants VO2max and speed lactate results. The various exercise bouts are split under ? different categories (Standing Okm / h, Walking 4km / h, Jogging Speed before lactate threshold, low speed 85% VO2max, moderate speed 100% VO2max, fast run 21 km / h, sprint 25 km / h), which were interspersed throughout the 45 min protocol in a mannerwhich replicated a football match. Throughout each 45-minute half the participants ran at a range of speeds between 0-25 km / h, simulating a football match. A venous blood and urine sample were collected at half-time and immediately post 90 mins. Finger prick blood samples were collected every 22.5 mins for lactate and glucose, while heart rate, oxygen saturation and core body temperature were recorded throughout the exercise task. Subjective assessment of gastrointestinal discomfort, RPE and thermal discomfort were assessed throughout the FSITP and were also assessed every 22.5 mins. Cognitive tests were conducted before, during half-time and post FSITP, this will include the stroop, visual search, memory block and rapid visual information processing test. Once the trial is completed the participants rested for another hour outside the environmental chamber and provided another blood sample at 60 mins post exercise.

[0596] Visit 4 & 7 - 24 hrs Post trial measurements

[0597] 24 hrs post exercise participants went to the laboratory having fasted overnight to provide a saliva sample and a venous blood sample for the analysis of l-FABP, LBP, Inflammation. Participants also provided a saliva sample for the analysis of IgA. A total of 20ml of blood was collected during these visits. A total of 480ml of blood was collected from each participant throughout the entire 8-week study. The supplement, either the prebiotic or placebo, was then continued for the next 42 days.

[0598] Visit 5

[0599] Participants went to the laboratory 3-weeks into the supplementation period to collect their remaining supplements and provide a saliva sample.

[0600] Procedures and measurements (e.g. materials and methods)

[0601] Height and mass

[0602] Height and body mass were measured using a stadiometer and weighing scales, respectively. Height and weight were measured in ERD 145 / 140 / 138. Body mass index (BMI) was calculated: BMI = mass (Kg) I heig ht2 (m2).

[0603] Blood Sample

[0604] Blood was sampled from an antecubital vein using a 21 G needle and vacutainer system prior to and post the repeated Wingate tests. 20 ml of blood was taken for assessment for plasma intestinal fatty acid binding protein (l-FABP), LPS binding protein, Ammonia, Interleukin cytokines and IgA. These markers provide evidence of intestinal damage, and markers of inflammation and immunity. Blood was centrifuged, and plasma stored at -80°C until further analysis via ELISA.

[0605] Saliva Sample Participants were asked to provide an unstimulated saliva sample by passive dribble for 2 minutes into a pre-weighed sterile collection tube for saliva immunoglobulin A (slgA). slgA is a protective marker in immune function. On collection the saliva samples were spun down (either immediately or with a few hours of collection) to produce an acellular saliva sample. The supernatant was removed and stored at - 80°C for further analysis. The cellular components from the saliva sample were disposed of within 24 h of collection. The supernatant was used for analysis of slgA via ELISA.

[0606] Oxygen saturation

[0607] Oxygen saturation was assessed using a portable pulse oximeter, attached to the left index finger during each measurement (Nonin Puresat; Minnesota, USA).

[0608] Heart rate

[0609] Heart rate was measured continuously using polar heart rate monitors. This involved participants wearing a heart rate monitor belt. This was fastened around the chest of each participant.

[0610] Subjective questionnaires

[0611] Gl discomfort during exercise

[0612] During exercise, Gl symptoms were assessed using a Gl discomfort scale. Global Gl symptoms were scored on a 9- point scale, with a score > 4 being regarded as serious. At the end of exercise participants completed a more detailed questionnaire in order to assess more specific symptoms of Gl discomfort during the session, such as bloating, flatulence and urge to vomit. Gl symptoms were scored on a 10-point scale (0 = no symptoms and 10 = extreme symptoms) with a score >4 being regarded as serious

[0613] Subjective rating Scales

[0614] Rating of perceived exertion (RPE) was measured on a 6 to 20 scale to measure perception of effort. Feeling will be measured using a -5 (Very bad) to +5 (Very good). Arousal will be measured using a 1 (low-arousal) to 6 (high-arousal). Thermal sensation (TS) will be measured using a 0 (Unbearably cold) to 8 (Unbearably hot) scale.

[0615] Upper respiratory tract infections (URTI) Symptoms During Supplementation

[0616] Each week participants completed a URTI symptom questionnaire. The questionnaire covers illness symptoms such as sore throat, catarrh (excessive mucus) in the throat, runny nose, cough, repetitive sneezing, fever, joint aches and pains, weakness, headache, and loss of sleep. Participants indicated each symptom as either light, moderate or severe (L, M, and S). The non-numerical ratings of L, M, and S were then scored as 1 , 2 or 3 to provide a quantitative means of data analysis. The total symptom score for each participant was calculated by multiplying the total number of days each symptom was experienced for by the numerical severity (1 , 2, or 3). In any given week a score > 12 will indicate a URTI was present. A single URTI episode will be defined as a period during which the weekly total symptom score was >12 and separated by at least 1 week from another week with a total symptom score >12.

[0617] Gastrointestinal Symptoms During Supplementation

[0618] Each week participants completed a Gl symptom questionnaire. The questionnaire covers symptoms underneath four categories; Overall Gl discomfort, Upper Gl symptoms, Lower Gl symptoms and Other Gl symptoms. Each symptom was rated on a 1-10 Likert scale, with 1-4 considered as “mild”, 5-9 as “severe” and 10 being “extremely severe”. This Gl symptom scale has been tested for validity and reliability in previous research.

[0619] Hydration

[0620] Urine osmolality will be measured at the beginning of each visit using a handheld urine osmometer (Osmometer-Osmocheck™; Vitech Scientific Ltd, West Sussex, UK) as an indicator of hydration status. A sample of ultra-pure water was pipetted on to the refractometer prior to each measurement in order to recalibrate the osmometer. Following removal of the water, a sample of urine was pipetted on to the osmometer and then measured for osmolality. Analyses were performed in duplicate. Any value < 800 mosmol.kgl will be considered as hydrated. If values exceeded 800 mosmol.kg-1 , participants were instructed to rest and consume water ad libitum and a sample was retaken to ensure hydration following 30 min of rest.

[0621] Core Body Temperature

[0622] Core body temperature was measured using an ingestible thermometric telemetric pill (Cranela Human Performance Ltd, UK) and wireless data logger. A wireless ingestible thermometric telemetric pill has been routinely used to assess core body temperature during exercise.

[0623] Cognitive Function Tests

[0624] All cognitive tests for each trial were completed in the allocated condition. Participants wore noise cancelling headphones in order to eradicate any distracting stimuli. Prior to each test, 3-6 practice stimuli were presented during which feedback was provided on the accuracy of the response. The purpose of these practice stimuli is to re-familiarise participants with the task and eradicate any learning effect, and the results for practice stimuli were not included in analysis.

[0625] Perception (Visual search test) Perception and visual processing were assessed using a visual search test. The test consists of two levels, each containing 21 stimuli. On the simple level of this test participants were required to respond to the appearance of a bold, solidly outlined green triangle. The complex level of the test was also made up of 21 stimuli, however, it required participants to respond to the appearance of a triangle shape made up of a number of dots. The background was comprised of green dots covering the screen, which were redrawn every 250ms to induce the visual effect of a flickering background. For both levels of the test the stimuli appeared at randomised locations across the screen at variable intervals. Participants were instructed to press the space bar in response to the stimulus as quickly as possible on both test levels. This test examines how well participants can filter distracting information from their surroundings and interpret specific cues, utilising visual processing and perception. The response time between the presentation of a stimulus and the response was recorded as well as the proportion of the correct responses achieved.

[0626] Executive Function (Stroop test)

[0627] The Stroop test is an executive function and selective attention task which measures frontal lobe function and the ability to suppress an automated response. The test is comprised of two levels, which have varying levels of interference. Each level involves a test word appearing in the centre of the screen, with a target word and a distractor either side of it. The target word’s position was counterbalanced for the left and right side within each test level and the participant was asked to respond as quickly as possible, using the left and right arrow key, to identify the target word’s position. The simple level of the test had 20 stimuli and the complex level was made up of 40. On the simple level of the Stroop test, the target word was the word matching the word in the centre of the screen, with all words presented in white font. The colour interference complex level of the test required the participant to select the word which corresponds with the colour the word in the centre of the screen was written in, rather than the word itself (which was an incongruent colour). The interstimulus interval was 1 s, and choices remained on the screen until a response was selected. Response time between the presentation of the stimuli and the response were recorded and the proportion of correct responses were measured.

[0628] Working Memory (Corsi Blocks) Test

[0629] The Corsi Blocks test assessed visuo-spatial shortterm working memory. A 3x3 grid filled the screen, where the squares randomly lit up. Participants were required to then replicate the order of the squares lighting up by clicking on the boxes. The sequence length started at three and with each correct response, the sequence got longer in length by 1 one unit. Where participants correctly recall a sequence of 9 boxes, the grid increased in size to 4x4. Performance was determined by the mean of the 3 longest correctly remembered sequences.

[0630] Attention (Rapid Visual Information Processing (RVIP) The RVIP test assesses sustained attention. The test lasted 5 min and numbers 2-9 appeared on the screen for the duration at 600ms intervals, with 8 target sequences appearing per min. Participants were instructed to press the space bar each time a sequence of 3 odd or even numbers were shown e.g. “2-4-6”, “3-5-7”, “9-3-7”, “8-4-2” and “4-6-8”. Responses could be registered during the last digit sequence and the 1500ms that followed. Response time from the presentation of the stimulus to the response were recorded, alongside the proportion of correct responses.

[0631] During each experimental trial, plasma intestinal fatty acid binding protein (l-FABP) were measured at baseline (B), half-time (HT), full-time (FT) and 60-min post full time (FT60). Salivary immunoglobulin A (slgA) secretion rate was measured at B and FT, and GIS for each half were measured at HT and FT. Throughout the 6-week intervention, daily URS and weekly GIS were selfreported using questionnaires.

[0632] Results

[0633] The A l-FABP following exercise, post-intervention compared to baseline was lower in the Bimuno GOS (B-GOS) than the Placebo (PLA) group (B-GOS: -358 ± 259 pg / mL; PLA: 218 ± 322 pg / mL; p < 0.001). For slgA secretion rate, the change as a result of exercise post intervention compared to baseline, was higher for the B-GOS compared to the Placebo group (B-GOS: 30.11 ± 85.83 pg / min; PLA: -42.09 ± 64.25 pg / min; p = 0.040). During exercise, there was a greater reduction in the total GIS score (severity of Gl symptoms) at the post-intervention visit in B-GOS than PLA (B-GOS: -16.7 ± 96.3 %; PLA: 13.3 ± 66.9 %; p = 0.021). There was no between-group difference in URS incidence, but duration (B-GOS: 3.4 ± 5.1 days; PLA: 9.0 ± 5.9 days; p = 0.025) and severity (B-GOS: 12 ± 16.5; PLA: 34.5 ± 22.5; p = 0.029) were lower for the B-GOS compared with the PLA group.

[0634] Example 5 - Example powder formulations

[0635] Different powder formulations were prepared where the % of GOS was about 76%. Table 5 below shows the different formulations which were prepared.

[0636] Table 5

[0637] Conclusion

[0638] Six weeks of a prebiotic B-GOS intervention improved Gl barrier resistance, GIS and maintained slgA secretion rate in response to football specific activity in the heat. There was also a reduction in the duration and severity of URS. These findings suggest that B-GOS has the potential to protect gut barrier function and modulate immune function, which may reduce the burden of illness and improve an athlete’s availability to train and compete.

[0639] Example 6

[0640] The aim of this study was to investigate the effects of a 6-week prebiotic intervention on gastrointestinal integrity, immunity, gastrointestinal symptoms (GIS) and upper respiratory symptoms (URS) following football specific exercise in the heat.

[0641] Methods

[0642] In a double-blind, randomised, placebo-controlled study, healthy recreationally active male team sport players (n=26) [age 23.6 ± 3.2 years, height 182.2 ± 6.9 cm, body mass 79.83 ± 9.28, VO2max 53.6 ± 4.7 mL kg-1min-1] were matched (by age and body mass) and randomised to receive 3.65 g / day of either Bimuno galacto-oligosaccharide prebiotic (B-GOS containing 2.75g active GOS; n=13) or a maltodextrin placebo (PLA; n=13) for 6 weeks (42 days). The volunteers were physically active, non-smokers, without a history of Gl illness, not regularly consuming foods enriched with prebiotic, probiotics or vitamins and regularly performed team sport activity (>4hrs of team sport activity per week). The composition of the B-GOS prebiotic used is in accordance with the present invention. The interventions were provided as single dose sachets in powdered form and were identical in taste and colour.

[0643] Before and after the 6-week (42 day) supplementation period, each volunteer completed an experimental trial where they underwent a football specific interval training protocol (FSITP) at 33°C which was designed to simulate playing a 90-minute football match in hot environmental conditions. The FSITP was comprised of two 45-minute periods separated by 15 minutes for half time. The FSITP was conducted in 33°C 50% relative humidity. During each experimental trial, plasma intestinal fatty acid binding protein (l-FABP), a marker of intestinal permeability, was measured before the FSITP (Pre), and then at half-time (HT), full-time (FT) and 60-min post full time (Post60).

[0644] Secretion rate of salivary immunoglobulin A (slgA), a marker of immune function, was measured before (Pre) and immediately after (FT) the FSITP, and GIS were recorded prior to commencing the FSITP, halfway through, as well as on completion of the protocol. Throughout the 6-week intervention, daily URS and weekly GIS were self-reported using validated questionnaires.

[0645] The study was conducted in accordance with the Declaration of Helsinki and approved by the Nottingham Trent University Human Invasive Ethics Committee (Ethics protocol ID 702). All subjects gave written informed consent prior to participating in the study.

[0646] Visit 1 - Baseline Visit

[0647] This comprised a health screening as well as speed lactate and maximal oxygen uptake testing. The results from the speed lactate and VO2max tests provided the speeds used for the stages of the FSITP.

[0648] Speed Lactate Test

[0649] Participants completed an incremental treadmill run starting at 9 km h -1 , 1 % gradient for 3 minutes, with the speed then increasing by 1 km h -1 every 3 minutes. At the end of each stage the participant stopped and a capillary blood sample was collected from the fingertip for the assessment of lactate. The test finished once MLSS threshold was achieved, which was defined as the fastest speed with less than a 1 mmol.L increase in [LaB] above the preceding levels (Astrand et al., 2003).

[0650] VO2max test

[0651] Following the speed lactate test, and after a 10-minute rest, participants then completed a VO2max test. Volunteers began running at their MLSS at a 1 % gradient, with an increase of 1 km h-1every minute until task failure. Throughout the maximal test, ventilatory and pulmonary variables were measured breath-by-breath using a metabolic cart (Vyntus CPX, Vyaire Medical Inc, United Kingdom), which was calibrated with the known gases (O2 = 15.96%, CO2 = 4.99%). Volunteers wore a facemask for the entirety of the test (Hans Rudolph 7450, Hans Rudolph Inc, USA) and expired air was sampled using a DVT flow, and O2 and CO2 sensors. For the ventilatory and pulmonary variables, ten second averages were calculated, with VO2max considered the highest VO2 value over any 10 second average.

[0652] Visit 2 - Familiarisation in the heat Visit 2 was at least one week after visit 1 , and participants completed a familiarisation trial where they performed one half of the FSITP in 33°C 50% relative humidity.

[0653] Visit 3 & 4 - Experimental visits

[0654] On days 0 and 42 (pre- and post the 6 week intervention period, respectively), participants underwent an experimental trial where they completed a 90-minute FSITP in 33°C 50% relative humidity.

[0655] Both visits were completed at the same time of day and participants were instructed to arrive 2 hours post-prandial and having consumed 500mL of water 2 hours prior to arrival. For the 24 hours preceding each experimental visit, volunteers consumed the same diet and were instructed to avoid exercise, alcohol, and caffeine intake.

[0656] At each visit, volunteers arrived at the laboratory and provided a urine sample for the assessment of hydration status via urine osmolality (Pocket-Pal Osmo-Osmocheck™, 4595-E04, Vitech Scientfic Ltd, Horsham, UK). Nude body mass (GFK 150 AEADAM digital scale, Vitech scientific Ltd) was then measured in private. Following a 10-min rest, samples of venous blood, capillary blood and saliva were collected. Resting HR and core temperature (Tcore) were then collected. Tcore was determined via an ingestible telemetric pill (e-celsius BodyCap, France) which was ingested 6 hours prior to the trial. Volunteers then completed the 90-minute FSITP in the heat chamber (33°C and 50% RH). The FSITP was made up of two 45-minute blocks of activity, separated by a 15-minute rest period to replicate half-time. A 3-minute water break was provided half-way through each half where participants could drink water ad-libitum (the amount consumed was recorded and repeated for the subsequent experimental trial). Every 5 minutes throughout the FSITP, HR, Tcore and rating of perceived exertion (RPE) (Borg et al., 1982) were recorded. Samples of venous and capillary blood were collected at half-time. Every 15 minutes, thermal sensation and fatigue were assessed using subjective questionnaires (Young et al., 1987; Micklewright et al., 2017). Nude body mass, urine, venous, capillary, and saliva samples were collected immediately after completion of the FSITP. After 60 minutes of rest, a final venous blood sample was collected. Each volunteer completed a gastrointestinal symptom questionnaire (Gaskell et al., 2019) before, at half-time and on completion of the FSITP. Following completion of the baseline / pre-intervention experimental trial (day 0 visit), the volunteers then began consuming either B-GOS or placebo daily for 6 weeks. The volunteers repeated the experimental trial after the 6-week intervention period (at day 42).

[0657] FSITP

[0658] The FSITP was performed on a motorised treadmill at a gradient of 1 %. The treadmill speeds were determined and customised according to the volunteer’s speed lactate and VO2max results. A total of 7 different speeds were incorporated into the protocol in order to simulate the intensity, accelerations and decelerations of a real football match and included: stationary (Okm h), walking (4km h), jogging (speed before MLSS), low speed (85% VO2max), moderate speed (100% VO2max), fast run (21 km h) and sprint (25 km h). Blood Samples

[0659] At each experimental trial visit, all volunteers provided blood samples prior (Pre), at half-time (HT), full time (FT) and 60 min post (Post60) the FSITP for the determination of plasma concentrations of l-FABP and LBP. Samples were drawn from the antecubital vein into three 6mL vacutainers, two of which contained EDTA and one contained a heparin anticoagulant. Samples were centrifuged immediately, and plasma aliquots frozen at -80°C until further analysis. I-FABP and LBP concentrations were determined using commercially available enzyme linked immunosorbent Assays (ELISA) (Hycult Biotech, Amsterdam, Netherlands).

[0660] Saliva Samples

[0661] At each experimental trial visit, saliva samples were collected before and immediately after (FT) the FSITP to determine salivary immunoglobulin A (slgA). Volunteers rinsed their mouth with plain water and rested for 10 minutes before producing a saliva sample via the passive drool method for 2 minutes. Samples were weighed and frozen immediately at -80°C until further analysis to determine slgA concentrations, which was achieved with a commercially available ELISA (Salimetrics, Philadelphia, PA). Considering flow rate influences slgA concentrations, slgA secretion rate was calculated: slgA concentration (pg / mL) was multiplied by the flow rate (volume / duration), resulting in a concentration measure per unit of time (pg / min).

[0662] Subjective questionnaires

[0663] Gl discomfort during exercise

[0664] GIS questionnaire data collected at half-time and full-time was used to determine the presence and severity of GIS during the FSITP (Gaskell et al., 2019). Volunteers were educated on the questionnaire and advised to rate the presence of each symptom over each 45-minute period using a 10-point visual analogue scale (0 = no symptoms, 10 = extremely severe). The questionnaire was adapted to incorporate 14 GIS, categorised as those associated with upper, lower and other GIS. The rating for each symptom was summed to give a total for each 45-minute period (i.e. for the first half and also for the second half of the FSITP). The scores for the two 45-minute periods (first half and second half) were then summed to provide an overall score during the FSITP. This process was repeated for the symptoms exclusive to the upper and lower Gl tract and those associated with neither (‘other symptoms’) (Gaskell et al., 2019).

[0665] Upper Respiratory Symptoms (URS) During Supplementation

[0666] To determine URS incidence and severity during the supplementation period, volunteers completed the Jackson questionnaire daily (Jackson et al., 1958). Over each 24-hour period, volunteers stated whether an upper respiratory illness was present and rated the severity of 8 symptoms (headache, chilliness, sneezing, sore throat, malaise, cough, nasal discharge, and nasal obstruction) on a scale of 0-3 (0-none, 1-mild, 2-moderate, 3-severe). Total Jackson score was calculated as the sum of the symptom scores for each day. The Jackson criteria as applied by Martineau et al. (2015) was used to define a URS episode, i.e. any period lasting > 3 days with a Jackson score of >14 and the presence of nasal discharge, or a symptom score < 14 with a subjective impression of having a cold for at least 3 days. If upper respiratory symptoms returned within a week it was regarded as the same episode. Duration of episodes was therefore also recorded. In addition, volunteers stated the use of any over the counter / prescribed medication during this period and if it impacted exercise.

[0667] Gastrointestinal Symptoms During Supplementation

[0668] To determine GIS incidence and severity during the supplementation period, volunteers completed the gastrointestinal symptom rating scale (GSRS) weekly. This involved rating the presence and severity of 15 GIS during the previous 7 days on a 7-point Likert scale from “no discomfort” to “very severe discomfort” (Svedlund et al., 1988).

[0669] Hydration

[0670] At each experimental trial visit, volunteers arrived at the laboratory and provided a urine sample for the assessment of hydration status via urine osmolality (Pocket-Pal Osmo-Osmocheck™, 4595-E04, Vitech Scientfic Ltd, Horsham, UK). During the FSITP, a 3 min water break was provided half-way through each half where volunteers could drink water ad-libitum, with the amount of water consumed recorded and repeated for the subsequent trial.

[0671] Core Body Temperature

[0672] Core body temperature (Tcore) was determined via an ingestible telemetric pill (e-celsius BodyCap, France), which was ingested by the volunteers 6 hours prior to the trial.

[0673] Results

[0674] Post-intervention (day 42), the peak A in l-FABP following the FSITP for the Bimuno group was significantly lower than for the Placebo group (mean rank of 9.85 for the B-GOS group and 15.64 for the Placebo group; / _2(1) = 3.995, p = 0.046), with a greater reduction (35.42%) vs at Day 0 for the B-GOS group compared to that observed for the Placebo group (figure 2).

[0675] The day 0 to day 42 pre-post FSITP mean change in slgA secretion rate was significantly different between B-GOS and Placebo groups, with an increase observed for the B-GOS group whilst a decrease was observed for the Placebo group (B-GOS: 74.00 ± 204.40 pg min-1; Placebo: -106.19 ± 124.60 pg min-1; p = 0.016) (figure 3).

[0676] There was a reduction in Total GIS severity during the FSITP post-intervention compared to baseline forthe B-GOS group which was not observed forthe Placebo group (B-GOS: -38.9 ± 24.2%; Placebo: 14.8 ± 65.4%; p = 0.009) (figure 4). For GIS subcategories, there was a reduction in “other GIS” severity scores from baseline to post-intervention for the B-GOS group but not the Placebo group (B-GOS: -34.6 ± 54.8%; Placebo: 32.5 ± 96.5%; p = 0.006). Furthermore, over the 6-week supplementation period, there was a significant attenuation in GIS severity forthe B-GOS compared to the Placebo group (B-GOS: -67.1 ± 36.1 %; Placebo: -4.8 ± 11 1 .1 ; p < 0.001).

[0677] The average duration of a URS episode was shorter in the B-GOS group compared to the Placebo group by 5.7 days (B-GOS: 3.2 ± 5.0 days; Placebo: 8.9 ± 5.4 days; p = 0.007). Also, the severity of URS episodes was reduced for the B-GOS group compared to the Placebo group (B-GOS: 11 .0 ± 16.1 ; Placebo: 32.3 ± 21.2; p = 0.017).

[0678] Table 6: Overview of self-reported URS data during the 6-week (42 day) intervention.

[0679] Conclusion

[0680] Six weeks of supplementation with prebiotic B-GOS reduced exercise-induced Gl damage and GIS during a simulated soccer match in the heat, which was accompanied with a greater maintenance of slgA immediately post-exercise. B-GOS also reduced URS severity and duration as well as GIS during the supplementation period. These findings suggest that B-GOS may enhance Gl barrier integrity during exercise, modulate immune function and reduce the burden of acute respiratory illness and Gl symptoms, which may improve athlete availability.

[0681] Although a few preferred embodiments have been shown and described, it will be appreciated by those skilled in the art that various changes and modifications might be made without departing from the scope of the invention, as defined in the appended claims.

[0682] Throughout this specification, the term “comprising” or “comprises” means including the component(s) specified but not to the exclusion of the presence of other components. The term “consisting essentially of’ or “consists essentially of’ means including the components specified but excluding other components except for materials present as impurities, unavoidable materials present as a result of processes used to provide the components, and components added for a purpose other than achieving the technical effect of the invention. Typically, when referring to compositions, a composition consisting essentially of a set of components will comprise less than 5% by weight, typically less than 3% by weight, more typically less than 1 % by weight of non-specified components.

[0683] The term “consisting of’ or “consists of’ means including the components specified but excluding addition of other components.

[0684] Whenever appropriate, depending upon the context, the use of the term “comprises” or “comprising” may also be taken to encompass or include the meaning “consists essentially of’ or “consisting essentially of’, and may also be taken to include the meaning “consists of’ or “consisting of’.

[0685] For the avoidance of doubt, wherein amounts of components in a composition are described in wt%, this means the weight percentage of the specified component in relation to the whole composition referred to. For example, “wherein the oligosaccharide compounds comprise up to 35 wt% of disaccharides” means that 35 wt% of the oligosaccharide compounds in the composition is provided by disaccharides.

[0686] The optional features set out herein may be used either individually or in combination with each other where appropriate and particularly in the combinations as set out in the accompanying claims. The optional features for each aspect or exemplary embodiment of the invention as set out herein are also to be read as applicable to any other aspect or exemplary embodiments of the invention, where appropriate. In other words, the skilled person reading this specification should consider the optional features for each exemplary embodiment of the invention as interchangeable and combinable between different exemplary embodiments.

[0687] Attention is directed to all papers and documents which are filed concurrently with or previous to this specification in connection with this application and which are open to public inspection with this specification, and the contents of all such papers and documents are incorporated herein by reference.

[0688] All of the features disclosed in this specification (including any accompanying claims, and drawings), and / or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and / or steps are mutually exclusive.

[0689] Each feature disclosed in this specification (including any accompanying claims, and drawings) may be replaced by alternative features serving the same, equivalent or similar purpose, unless expressly stated otherwise. Thus, unless expressly stated otherwise, each feature disclosed is one example only of a generic series of equivalent or similar features.

[0690] The invention is not restricted to the details of the foregoing embodiment(s). The invention extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims, and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed.

Claims

Claims1. A composition comprising oligosaccharide compounds for use in the prevention, amelioration and / or treatment of gastrointestinal discomfort, gastrointestinal damage and / or upper respiratory episodes occurring during and / or after athletic activity in extreme environmental conditions, wherein the oligosaccharide compounds comprise:(a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;(b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and(c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc, based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xband Xcare each independently selected from monosaccharides.

2. The composition for use according to claim 1 , wherein the oligosaccharide compounds comprise:(d) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Gal-(p1-4)-Xd, based on the total weight of oligosaccharide compounds present in the composition; wherein Xd, is selected from monosaccharides.

3. The composition for use according to claim 1 or claim 2, wherein: component (a) is present in an amount up to 35 wt%; component (b) is present in an amount up to 25 wt%; and component (c) is present in an amount up to 25 wt%; based on the total weight of oligosaccharide compounds present in the composition.

4. The composition for use according to any one of the preceding claims, wherein the ratio of the wt% of compound (a) to compound (b) is from 1 :1 to 3:1 .

5. The composition for use according to any one of the preceding claims, wherein the ratio of the wt% of compound (a) to compound (c) is from 1 :1 to 3:1 .

6. The composition for use according to any one of the preceding claims, wherein the ratio of the wt% of compound (b) to compound (c) is from 2:1 to 1 :2.

7. The composition for use according to any one of the preceding claims, wherein the oligosaccharide compounds comprise:(e) at least 5 wt% Gal-(p1-4)-Gal-(p1-4)-Xe; based on the total weight of oligosaccharide compounds present in the composition; wherein Xeis selected from monosaccharides.

8. The composition for use according to any one of the preceding claims, wherein Xa, Xb, Xc, Xdand Xeare each independently selected from glucose, fucose, arabinose, xylose, rhamnose, mannose, galactose, ribose, lyxose, allose, altrose, gulose, idose, talose, psicose, fructose, sorbose, tagatose, galactosamine, glucosamine and N-Acetylglucosamine or mixtures thereof.

9. The composition for use according to any one of claims 1 to 7, wherein Xa, Xb, Xc, Xdand Xeare each Glc.

10. The composition for use according to any one of claims 1 to 7, wherein Xa, Xb, Xc, Xdand Xeeach comprise Fuc.11 . The composition for use according to any one of the preceding claims, wherein from 40 to 55% of the Gal-Gal linkages in the oligosaccharide compounds are p1 -3 linkages.

12. The composition for use according to any one of the preceding claims, comprising at least 50 wt% of the oligosaccharide compounds, preferably wherein the composition is in the form of a syrup.

13. The composition for use according to any one of the preceding claims, comprising at least 75 wt% of the oligosaccharide compounds, preferably wherein the composition is in the form of a powder.

14. The composition for use according to any one of the preceding claims, wherein the oligosaccharide compounds comprise at least 25 wt% of trisaccharides.

15. The composition for use according to any one of the preceding claims, wherein the oligosaccharide compounds comprise at least 10 wt% of tetrasaccharides.

16. The composition for use according to any one of the preceding claims, comprising 80 wt% of trisaccharides, tetrasaccharides and higher oligosaccharides.

17. The composition for use according to any one of the preceding claims, comprising 80 wt% of trisaccharides.

18. The composition for use according to any one of the preceding claims, wherein the composition is in the form of one or more of the following: a dietary supplement, a medical food and / or nutritional product, and a food for specific medical purposes.

19. The composition for use according to any one of claims 1 to 17, wherein the composition is in the form of a pharmaceutical or nutraceutical.

20. The composition for use according to claim 19, wherein the pharmaceutical or nutraceutical further comprises at least one carrier, excipient, or diluent.

21. The composition for use according to preceding claim, for administration to any person or an athlete or sports person who is undergoing and / or about to undergo, physical training.

22. A composition comprising oligosaccharide compounds for use in the reduction of plasma l-FABP during and / or after athletic activity in extreme environmental conditions, wherein the oligosaccharide compounds comprise:(a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;(b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and(c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc, based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xband Xcare each independently selected from monosaccharides.

23. A composition comprising oligosaccharide compounds for use in the increase of salivary immunoglobulin A (slgA) during and / or after athletic activity in extreme environmental conditions, wherein the oligosaccharide compounds comprise:(a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;(b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and(c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc, based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xband Xcare each independently selected from monosaccharides.

24. A method of reducing plasma l-FABP during and / or after athletic activity in extreme environmental conditions in a subject the method comprising: i) administrating a therapeutically effective amount of a composition comprising oligosaccharide compounds to the subject, wherein the oligosaccharide compounds comprise:(a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;(b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and(c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc, based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xband Xcare each independently selected from monosaccharides.

25. A method of increasing salivary immunoglobulin A (slgA) during and / or after athletic activity in extreme environmental conditions in a subject the method comprising: i) administrating a therapeutically effective amount of a composition comprising oligosaccharide compounds to the subject, wherein the oligosaccharide compounds comprise:(a) at least 8 wt% Gal-(p1-3)-Gal-(p1-4)-Xa;(b) at least 3 wt% Gal-(p1-3)-Gal-(p1-3)-Xb; and(c) at least 5 wt% Gal-(p1-3)-Gal-(p1-2)-Xc, based on the total weight of oligosaccharide compounds present in the composition; wherein Xa, Xband Xcare each independently selected from monosaccharides.

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