Systematic review: exercise-induced gastrointestinal syndrome—implications for health and intestinal disease

Alimentary Pharmacology and Therapeutics

Volumn 46, Issue 3, 2017, Pages 246-265

  Costa, R J S ^a   Snipe, R M J ^a   Kitic, C M ^b   Gibson, P R ^a  

^a MONASH UNIVERSITY   (Australia)

^b UNIVERSITY OF TASMANIA   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIOXIDANT; ARGININE; CITRULLINE; GLUTAMINE; PLACEBO; PROBIOTIC AGENT; BIOLOGICAL MARKER;

BIFIDOBACTERIUM; COLOSTRUM; CYCLING; DIET SUPPLEMENTATION; DIETARY SUPPLEMENT; DIGESTIVE SYSTEM FUNCTION DISORDER; DIGESTIVE SYSTEM INJURY; DRUG EFFECT; ENDOTOXEMIA; ENDURANCE TRAINING; EXERCISE; EXERCISE INDUCED GASTROINTESTINAL SYNDROME; EXERCISE INTENSITY; GASTROINTESTINAL DISEASE; GASTROINTESTINAL MOTILITY; GASTROINTESTINAL TRANSIT; HEAT STRESS; HUMAN; INCIDENCE; INFLAMMATORY BOWEL DISEASE; INTESTINE INJURY; INTESTINE MUCOSA PERMEABILITY; LACTOBACILLUS; MALABSORPTION; PRIMARY PREVENTION; PRIORITY JOURNAL; RESISTANCE TRAINING; REVIEW; RUNNING; STOMACH EMPTYING; STREPTOCOCCUS; SYSTEMATIC REVIEW; CHRONIC DISEASE; ENTEROPATHY; PATHOLOGY; PATHOPHYSIOLOGY; PERMEABILITY; SMALL INTESTINE;

BIOMARKERS; CHRONIC DISEASE; EXERCISE; GASTRIC EMPTYING; GASTROINTESTINAL DISEASES; HUMANS; INTESTINAL DISEASES; INTESTINE, SMALL; PERMEABILITY;

EID: 85020228181     PISSN: 02692813     EISSN: 13652036     Source Type: Journal    
DOI: 10.1111/apt.14157     Document Type: Review

References (141)

1. World Health Organisation. Global recommendations on physical activity for health. WHO Library Cataloguing-in-Publication Data. Press, Geneva, Switzerland: World Health Organization; 2010.
2. Bull FC, and the Expert Working Groups. Physical Activity Guidelines in the U.K.: Review and Recommendations. Loughborough, United Kingdom: School of Sport, Exercise and Health Sciences, Loughborough University; 2010.
3. Brown WJ, Bauman AE, Bull FC, Burton NW. Development of Evidence-based Physical Activity Recommendations for Adults (18-64 years). Report prepared for the Australian Government Department of Health 2012.
4. Physical Activity Guideline Advisory Committee. Physical Activity Guidelines Advisory Committee Report. Washington (DC): US Department of Health and Human Services; 2008. p. 23.
5. Ainsworth BE, Haskell WL, Whitt MC, et al. Compendium of physical activities: an update of activity codes and met intensities. Med Sci Sports Exerc. 2000;32:s498-s516.
6. Ainsworth BE, Haskell WL, Herrmann SD, et al. Compendium of physical activities: a second update of codes and met values. Med Sci Sports Exerc. 2011;43:1575-1581.
7. ter Steege RWF, Van Der Palen J, Kolkman JJ. Prevalence of gastrointestinal complaints in runners competing in a long-distance run: an internet-based observational study in 1281 subjects. Scand J Gastroenterol. 2008;43:1477-1482.
8. ter Steege RW, Kolkman JJ. The pathophysiology and management of gastrointestinal symptoms during physical exercise, and the role of splanchnic blood flow. Aliment Pharmacol Ther. 2012;35:516-528.
9. Grootjans J, Lenaerts K, Buurman WA, Dejong CH, Derikx JP. Life and death at the mucosal-luminal interface: new perspectives on human intestinal ischemia-reperfusion. World J Gastroenterol. 2016;22:2760-2770.
10. Lang JA, Gisolfi CV, Lambert GP. Effect of exercise intensity on active and passive glucose absorption. Int J Sport Nutr Exerc Metab. 2006;16:485-493.
11. Leiper JB. Fate of ingested fluids: factors affecting gastric emptying and intestinal absorption of beverages in humans. Nutr Rev. 2015;73(S2):57-72.
12. van Wijck K, Lenaerts K, Grootjans J, et al. Physiology and pathophysiology of splanchnic hypoperfusion and intestinal injury during exercise: strategies for evaluation and preventions. Am J Physiol. 2012;303:G155-G168.
13. Knoth C, Knechtle B, Rust CA, et al. Participation and performance trends in multi-stage ultra-marathon- the ‘Marathon des Sables’ 2003-2012. Extreme Physiol Med. 2012;1:1-11.
14. Costa RJS, Snipe R, Camões-Costa V, Scheer BV, Murray A. The impact of gastrointestinal symptoms and dermatological injuries on nutritional intake and hydration status during ultramarathon events. Sports Med- Open. 2016;2:1-14.
15. Jeukendrup AE, Vet-Joop K, Sturk A, et al. Relationship between gastro-intestinal complaints and endotoxaemia, cytokine release and the acute-phase reaction during and after a long-distance triathlon in highly trained men. Clin Sci. 2000;98:47-55.
16. Stuempfle KJ, Hoffman MD. Gastrointestinal distress is common during a 161-km ultramarathon. J Sports Sci. 2015;33:1814-1821.
17. Peake JM, Della Gatta P, Suzuki K, Nieman DC. Cytokine expression and secretion by skeletal muscle cells: regulatory mechanisms and exercise effects. Exerc Immunol Rev. 2015;21:8-25.
18. Horner KM, Schubert MM, Desbrow B, Byrne NM, King NA. Acute exercise and gastric emptying: a meta-analysis and implications for appetite control. Sports Med. 2015;45:659-678.
19. Costa RJS, Miall A, Khoo A, et al. Gut-training: the impact of two weeks repetitive gut-challenge during exercise on gastrointestinal status, glucose availability, fuel kinetics, and running performance. Appl Physiol Nutri Metab 2017. (In press).
20. van Wijck K, Lenaerts K, van Loon LJ, et al. Exercise-induced splanchnic hypoperfusion results in gut dysfunction in healthy men. PLoS ONE. 2011;6:e22366.
21. Rehrer NJ, Smets A, Reynaert H, Goes E, De Meirleir K. Effect of exercise on portal vein blood flow in man. Med Sci Sports Exerc. 2001;33:1533-1537.
22. van der Flier LG, Clevers H. Stem cells, self-renewal, and differentiation in the intestinal epithelium. Annu Rev Physiol. 2009;71:241-260.
23. Zuhl M, Schneider S, Lanphere K, Conn C, Dokladny K, Moseley P. Exercise regulation of intestinal tight junction proteins. Br J Sports Med. 2014;48:980-986.
24. Dokladny K, Zuhl MN, Moseley PL. Intestinal epithelial barrier function and tight junction proteins with heat and exercise. J Appl Physiol. 2016;120:692-701.
25. Irving AT, Mimuro H, Kufer TA, et al. The immune receptor NOD1 and kinase RIP2 interact with bacterial peptidoglycan on early endosomes to promote autophagy and inflammatory signaling. Cell Host Microbe. 2014;15:623-635.
26. Kaparakis-Liaskos M, Ferrero RL. Immune modulation by bacterial outer membrane vesicles. Nat Rev Immunol. 2015;15:375-387.
27. Capaldo CT, Nusrat A. Cytokine regulation of tight junctions. Biochim Biophys Acta. 2009;1788:864-871.
28. Camus G, Poortmans J, Nys M, et al. Mild endotoxaemia and the inflammatory response induced by a marathon race. Clin Sci. 1997;92:415-422.
29. Gill SK, Hankey J, Wright A, et al. The impact of a 24-hour ultra-marathon on circulatory endotoxin and cytokine profile. Int J Sports Med. 2015;36:688-695.
30. Gill SK, Teixeira A, Rama L, et al. Circulatory endotoxin concentration and cytokine profile in response to exertional-heat stress during a multi-stage ultra-marathon competition. Exerc Immunol Rev. 2015;21:114-128.
31. Kulp A, Kuehn MJ. Biological functions and biogenesis of secreted bacterial outer membrane vesicles. Ann Rev Microbiol. 2010;64:163-184.
32. Barclay GR. Endogenous endotoxin-core antibody (EndoCAb) as a marker of endotoxin exposure and a prognostic indicator: a review. Prog Clin Biol Res. 1995;392:263-272.
33. Buttenschoen K, Berger D, Hiki N, et al. Plasma concentrations of endotoxin and antiendotoxin antibodies in patients with multiple injuries: a prospective clinical study. Eur J Surg. 1996;162:853-860.
34. Bosenberg AT, Brock-Utne JG, Gaffin SL, Wells MT, Blake GT. Strenuous exercise causes systemic endotoxemia. J Appl Physiol. 1988;65:106-108.
35. Lim CL, Pyne D, Horn P, et al. The effects of increased endurance training load on biomarkers of heat intolerance during intense exercise in the heat. Appl Physiol Nutr Metab. 2009;34:616-624.
36. Wittkopf N, Neurath MF, Becker C. Immune-epithelial crosstalk at the intestinal surface. J Gastroenterol. 2014;49:375-387.
37. van Wijck K, Pennings B, van Bijnen AA, et al. Dietary protein digestion and absorption are impaired during acute postexercise recovery in young men. Am J Phyiol Regul Integr Comp Physiol. 2013;304:R356-R361.
38. Peters HP, Schep G, Koster DJ, Douwes AC, de Vried WR. Hydrogen breath test as a simple noninvasive method for evaluation of carbohydrate malabsorption during exercise. Eur J Appl Physiol Occup Physiol. 1994;68:435-440.
39. Putkonen L, Yao CK, Gibson PR. Fructose malabsorption syndrome. Curr Opin Clin Nutr Metab Care. 2013;6:473-477.
40. Yao CK, Muir JG, Gibson PR. Review article: insights into colonic protein fermentation, its modulation and potential health implications. Aliment Pharmacol Ther. 2016;43:181-196.
41. Layer P, Peschel S, Schlesinger T, Goebell H. Human pancreatic secretion and intestinal motility: effects of ileal nutrient perfusion. Am J Physiol Gastrointest Liver Physiol. 1990;258:G196-G201.
42. Shin HS, Ingram JR, McGill AT, Poppitt SD. Lipids, CHOs, proteins: can all macronutrients put a ‘brake’ on eating? Physiol Behav. 2013;120:114-123.
43. Porter J, Adderley M, Bonham M, et al. The effect of dietary interventions and nutritional supplementation on bone mineral density in otherwise healthy adults with osteopenia: a systematic review. Nutr Bulletin. 2016;41:108-121.
44. Sessions J, Bourbeau K, Rosinski M, et al. Carbohydrate gel ingestion during running in the heat on markers of gastrointestinal distress. Eur J Sport Sci. 2016;16:1064-1072.
45. van Wijck K, Lenaerts K, Van Bijnen AA, et al. Aggravation of exercise-induced intestinal injury by Ibuprofen in athletes. Med Sci Sports Exerc. 2012;44:2257-2262.
46. Lis D, Stellingwerff T, Kitic CM, Ahuja KD, Fell J. No effects of a short-term gluten-free diet on performance in nonceliac athletes. Med Sci Sports Exerc. 2015;47:2563-2570.
47. Morrison SA, Cheung SS, Cotter JD. Bovine colostrum, training status, and gastrointestinal permeability during exercise in the heat: a placebo-controlled double-blind study. Appl Physiol Nutr Metab. 2014;39:1070-1082.
48. Barberio MD, Elmer DJ, Laird RH, et al. Systemic LPS and inflammatory response during consecutive days of exercise in heat. Int J Sports Med. 2015;36:262-270.
49. Peters HP, Wiersma WC, Akkermans LM, et al. Gastrointestinal mucosal integrity after prolonged exercise with fluid supplementation. Med Sci Sports Exerc. 2000;32:134-142.
50. Murray R. Training the gut for competition. Curr Sports Med Rep. 2006;5:161-164.
51. Robertson JD, Maughan RJ, Davidson RJ. Faecal blood loss in response to exercise. Br Med J. 1987;295:303-305.
52. Pals KL, Chang RT, Ryan AJ, Gisolfi CV. Effect of running intensity on intestinal permeability. J Appl Physiol. 1997;82:571-576.
53. Lambert GP. Role of gastrointestinal permeability in exertional heatstroke. Exerc Sport Sci Rev. 2004;32:185-190.
54. Yeh Y, Law L, Lim C. Gastrointestinal response and endotoxemia during intense exercise in hot and cool environments. Eur J Appl Physiol. 2013;113:1575-1583.
55. Lambert CP, Lang J, Bull A, et al. Fluid restriction during running increases GI permeability. Int J Sports Med. 2008;29:194-198.
56. Zuhl MN, Lanphere KR, Kravitz L, et al. Effects of oral glutamine supplementation on exercise-induced gastrointestinal permeability and tight junction protein expression. J Appl Physiol. 2014;116:183-191.
57. Buchman AL, Killip D, Ou CN, et al. Short-term vitamin E supplementation before marathon running: a placebo-controlled trial. Nutr. 1999;15:278-283.
58. Triantafilou M, Triantafilou K. Lipopolysaccharide recognition: CD14, TLRs and the LPS-activation cluster. Trends Immunol. 2002;23:301-304.
59. Diks SH, van Deventer SJ, Peppelenbosch MP. Lipopolysaccharide recognition, internalisation, signalling and other cellular effects. J Endotoxin Res. 2001;7:335-348.
60. Brock-Utne JG, Gaffin SL, Wells MT, et al. Endotoxemia inexhausted runners after a long-distance race. S Afr Med J. 1988;73:533-536.
61. Camus G, Nys M, Poortmans JR, et al. Endotoxemia production of tumor necrosis factor alpha and polymorphonuclear neutrophil activation following strenuous exercise in humans. Eur J Appl Physiol. 1998;79:62-68.
62. Nieman DC, Henson DA, Dumke CL, et al. Ibuprofen use, endotoxemia, inflammation, and plasma cytokines during ultramarathon competition. Brain Behav Immun. 2006;20:578-584.
63. Zuhl M, Dokladny K, Mermier C, et al. The effects of acute oral glutamine supplementation on exercise-induced gastrointestinal permeability and heat shock protein expression in peripheral blood mononuclear cells. Cell Stress Chaperones. 2015;20:85-93.
64. Ng QY, Lee KW, Byrne C, Ho TF, Lim CL. Plasma endotoxin and immune responses during a 21-km road race under a warm and humid environment. Ann Acad Med Singapore. 2008;37:307-314.
65. Shing CM, Peake JM, Lim CL, et al. Effects of probiotics supplementation on gastrointestinal permeability, inflammation and exercise performance in the heat. Eur J Appl Physiol. 2014;114:93-103.
66. Ashton T, Young IS, Davison GW, et al. Exercise-induced endotoxemia: the effect of ascorbic acid supplementation. Free Radic Biol Med. 2003;35:284-291.
67. Gill SK, Allerton DM, Ansley-Robson P, et al. Does acute high dose probiotic supplementation containing Lactobacillus casei attenuate exertional-heat stress induced endotoxaemia and cytokinaemia? Int J Sports Nutr Exerc Metab. 2016;26:268-275.
68. Guy JH, Pyne DB, Deakin GB, Miller CM, Edwards AM. Acclimation training improves endurance cycling performance in the heat without inducing endotoxemia. Front Physiol. 2016;7:318.
69. Stuempfle KJ, Valentino T, Hew-Butler T, Hecht FM, Hoffman MD. Nausea is associated with endotoxemia during a 161-km ultramarathon. J Sports Sci. 2016;34:1662-1668.
70. Moore GE, Holbein ME, Knochel JP. Exercise-associated collapse in cyclists is unrelated to endotoxemia. Med Sci Sports Exerc. 1995;27:1238-1242.
71. Costa RJS. Exercise-induced gastrointestinal syndrome: does the intestinal microbiome have a role to play? Australian Academy of Science- Microbiome Symposium, 2016.
72. Mariadason JM, Barkla DH, Gibson PR. Effect of short-chain fatty acids on paracellular permeability in Caco-2 intestinal epithelium model. Am J Physiol. 1997;272:G705-G712.
73. Mariadason JM, Catto-Smith A, Gibson PR. Modulation of distal colonic epithelial barrier function by dietary fibre in normal rats. Gut. 1999;44:394-399.
74. Wilson AJ, Gibson PR. Short-chain fatty acids promote the migration of colonic epithelial cells in vitro. Gastroenterol. 1997;113:487-496.
75. Arumugam M, Raes J, Pelletier E, et al. Enterotypes of the human gut microbiome. Nature. 2011;473:174-180.
76. Sekirov I, Russell SL, Antunes LC, Finlay BB. Gut microbiota in health and disease. Physiol Rev. 2010;90:859-904.
77. David LA, Maurice CF, Carmody RN, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505:559-563.
78. Halmos EP, Christophersen CT, Bird AR, et al. Diets that differ in their FODMAP content alter the colonic luminal microenvironment. Gut. 2015;64:93-100.
79. Lee T, Clavel T, Smirnov K, et al. Oral versus intravenous iron replacement therapy distinctly alters the gut microbiota and metabolome in patients with IBD. Gut. 2017;66:863-871.
80. Clarke SF, Murphy EF, O'Sullivan O, et al. Exercise and associated dietary extremes impact on gut microbial diversity. Gut. 2014;63:1913-1920.
81. Bressa C, Bailén-Andrion M, Pérez-Santiago J, et al. Differences in gut microbiota profile between women with active lifestyle and sedentary women. PLoS ONE 2017;12:e0171352.
82. Hew-Butler T, Verbalis JG, Noakes TD. International Marathon Medical Directors Association, Updated fluid recommendation: position statement from the International Marathon Medical Directors Association (IMMDA). Clin J Sport Med. 2006;16:283-292.
83. Stellingwerff T, Cox GR. Systematic review: carbohydrate supplementation on exercise performance or capacity of varying durations. Appl Physiol Nutr Metab. 2014;39:1-14.
84. Evans GH, Watson P, Shirreffs SM, Maughan RJ. Effect of exercise intensity on subsequent gastric emptying rate in humans. Int J Sport Nutr Exerc Metab. 2016;26:128-134.
85. Kuznetsov AP, Kozhevnikov VI, Rechkalov AV. Radioisotopic investigation of gastric emptying and small intestine function at different exercise levels. In: Rogozkin VA, Maughan R, eds. Current Research in Sports Sciences. An International Perspective. New York: Plenum Press Div Plenum Publishing Corp; 1996. 339-43 p.
86. Leiper JB, Prentice AS, Wrightson C, Maughan RJ. Gastric emptying of a carbohydrate-electrolyte drink during a soccer match. Med Sci Sports Exerc. 2001;33:1932-1938.
87. Leiper JB, Broad NP, Maughan RJ. Effect of intermittent high-intensity exercise on gastric emptying in man. Med Sci Sports Exerc. 2001;33:1270-1278.
88. Leiper JB, Nicholas CW, Ali A, Willimas C, Maughan RJ. The effect of intermittent high-intensity running on gastric emptying of fluids in man. Med Sci Sports Exerc. 2005;37:240-247.
89. Strid H, Simrén M, Störsrud S, Stotzer P-O, Sadik R. Effect of heavy exercise on gastrointestinal transit in endurance athletes. Scand J Gastroentero. 2011;46:673-677.
90. van Nieuwenhoven MA, Brouns F, Brummer RJ. The effect of physical exercise on parameters of gastrointestinal function. Neurogastroenterol Motil. 1999;11:431-439.
91. van Nieuwenhoven MA, Brouns F. Brummer R-JM. Gastrointestinal profile of symptomatic athletes at rest and during physical exercise. Eur J Appl Physiol. 2004;91:429-434.
92. Kato M, Sakai T, Yabe K, Miyamura M, Soya H. Gastric myoelectrical activity increases after mderate-intensity exercise with no meals under suppressed vagal nerve activity. Japan J Physiol. 2004;54:221-228.
93. Lu CL, Shidler N, Chen JDZ. Enhanced postprandial gastric myoelectrical activity after moderate-intensity exercise. Am J Gastroenterol. 2000;95:425-431.
94. Wang Y, Kondo T, Suzukamo Y, Oouchida Y, Izumi SI. Vagal nerve regulation is essential for the increase in gastric motility in response to mild exercise. Tohoku J Exp Med. 2010;222:155-163.
95. Camilleri M, Malagelada JR, Kao PC, Zinsmeister AR. Gastric and autonomic responses to stress in functional dyspepsia. Dig Dis Sci. 1986;31:1169-1177.
96. Song GQ, Sun Y, Foreman RD, Chen JD. Therapeutic potential of spinal cord stimulation for gastrointestinal motility disorders: a preliminary rodent study. Neurogastroenterol Motil. 2014;26:377-384.
97. Browning KN, Travagli RA. Central nervous system control of gastrointestinal motility and secretion and modulation of gastrointestinal functions. Compr Physiol. 2014;4:1339-1368.
98. van Loon LJ, Boirie Y, Gijsen AP, et al. The production of intrinsically labeled milk protein provides a functional tool for human nutrition research. J Dairy Sci. 2009;92:4812-4822.
99. Gasbarrini A, Corazza GR, Gasbarrini G, et al. Methodology and indications of H2-breath testing in gastrointestinal diseases: the Rome Consensus Conference. 1st Rome H2-Breath Testing Consensus Conference Working Group. Aliment Pharmacol Ther. 2009;29(Suppl 1):1-49.
100. Bate JP, Irving PM, Barrett JS, Gibson PR. Benefits of breath hydrogen testing after lactulose administration in analysing carbohydrate malabsorption. Eur J Gastroenterol Hepatol. 2010;22:318-326.
101. Grames C, Berry-Cabán CS. Ischemic colitis in an endurance runner. Case Rep. Gastrointest Med. 2012;2012:356895.
102. Pfeiffer B, Stellingwerff T, Hodgson AB, et al. Nutritional intake and gastrointestinal problems during competitive endurance events. Med Sci Sports Exerc. 2012;44:344-351.
103. Stuempfle KJ, Hoffman MD, Hew-Butler T. Association of gastrointestinal distress in ultramarathoners with race diet. Int J Sport Nutr Exerc Metab. 2013;23:103-109.
104. Bilski J, Mazur-Bialy A, Brzozowski B, et al. Can exercise affect the course of inflammatory bowel disease? Experimental and clinical evidence. Pharmacol Rep. 2016;68:827-836.
105. Martin D. Physical activity benefits and risks on the gastrointestinal system. South Med J. 2011;104:831-837.
106. Shephard RJ. The case for increased physical activity in chronic inflammatory bowel disease: a brief review. Int J Sports Med. 2016;37:505-515.
107. Klare P, Nigg J, Nold J, et al. The impact of a ten-week physical exercise program on health-related quality of life in patients with inflammatory bowel disease: a prospective randomized controlled trial. Digest. 2015;91:239-247.
108. Ng V, Millard W, Lebrun C, Howard J. Low-intensity exercise improves quality of life in patients with Crohn's disease. Clin J Sport Med. 2007;17:384-388.
109. Loudon CP, Corroll V, Butcher J, Rawsthorne P, Bernstein CN. The effects of physical exercise on patients with Crohn's disease. Am J Gastroenterol. 1990;94:697-703.
110. Johannesson E, Simrén M, Strid H, Bajor A, Sadik R. Physical activity improves symptoms in irritable bowel syndrome: a randomized controlled trial. Am J Gastroenterol. 2011;106:915-922.
111. Johannesson E, Ringström G, Abrahamsson H, Sadik R. Intervention to increase physical activity in irritable bowel syndrome shows long-term positive effects. World J Gastroenterol. 2015;21:600-608.
112. Villoria A, Serra J, Azpiroz F, Malagelada JR. Physical activity and intestinal gas clearance in patients with bloating. Am J Gastroenterol. 2006;101:2552-2557.
113. D'Inca R, Varnier M, Mestriner C, et al. Effect of moderate exercise on Crohn's disease patients in remission. Ital J Gastroenterol Hepatol. 1999;31:205-210.
114. Ploeger H, Obeid J, Nguyen T, et al. Exercise and inflammation in pediatric Crohn's disease. Int J Sports Med. 2012;33:671-679.
115. Bahrami B, Macfarlane S, Macfarlane GT. Induction of cytokine formation by human intestinal bacteria in gut epithelial cell lines. J Appl Microbiol. 2011;110:353-363.
116. Eri RD, Adams RJ, Tran TV, et al. An intestinal epithelial defect conferring ER stress results in inflammation involving both innate and adaptive immunity. Mucosal Immunol. 2011;4:354-364.
117. DeFilippis EM, Tabani S, Warren RU, et al. Exercise and Self-Reported Limitations in Patients with Inflammatory Bowel Disease. Dig Dis Sci. 2016;61:215-220.
118. Costa RJS, Swancott A, Gill S, et al. Compromised energy and nutritional intake of ultra-endurance runners during a multi-stage ultra-marathon conducted in a hot ambient environment. Int J Sports Sci. 2013;3:51-61.
119. Costa RJS, Gill SK, Hankey J, Wright A, Marczak S. Perturbed energy balance and hydration status in ultra-endurance runners during a 24 h ultra-marathon. Br J Nutri. 2014;112:428-437.
120. van Nieuwenhoven MA, Vriens BE, Brummer RJ, Brouns F. Effect of dehydration on gastrointestinal function at rest and during exercise in humans. Eur J Appl Physiol. 2000;83:578-584.
121. Ryan AJ, Lambert GP, Shi X, et al. Effect of hypohydration on gastric emptying and intestinal absorption during exercise. J Appl Physiol. 1998;84:1581-1588.
122. Hoffman MD, Pasternak A, Rogers IR, et al. Medical services at ultra-endurance food races in remote environments: medical issues and consensus guidelines. Sports Med. 2014;44:105-1069.
123. Hew-Butler T, Rosner MH, Fowkes-Godek S, et al. Statement of the 3rd international exercise-associated hyponatremia consensus development conference, Carlsbad, California, 2015. Br J Sports Med. 2015;49:1432-1446.
124. Matherson PJ, Wilson MA, Garrison RN. Regulation of intestinal blood flow. J Surg Res. 2000;93:182-196.
125. Rehrer NJ, Goes E, DuGardeyn C, Reynaert H, DeMeirleir K. Effect of carbohydrate on portal vein blood flow during exercise. Int J Sports Med. 2005;26:171-176.
126. Lambert GP, Broussard LJ, Mason BL, Mauermann WJ, Gisolfi CV. Gastrointestinal permeability during exercise: effects of aspirin and energy-containing beverages. J Appl Physiol. 2001;90:2075-2080.
127. Snipe R, Kitic C, Gibson P, Costa RJS. Carbohydrate and protein intake during exertional-heat stress ameliorates intestinal epithelial damage. Nutri Diet 2016;73(Suppl 1):19. abstract
128. Thomas DT, Erdman KA, Burke LM. American college of sports medicine joint position statement. Nutrition and athletic performance. Med Sci Sports Exerc. 2016;48:543-568.
129. Lis DM, Stellingwerff T, Shing CM, Ahuja KD, Fell JW. Exploring the popularity, experiences, and beliefs surrounding gluten-free diets in nonceliac athletes. Int J Sport Nutr Exerc Metab. 2015;25:37-45.
130. Lis D, Ahuja KD, Stellingwerff T, Kitic CM, Fell J. Case study: utilizing a low FODMAP diet to combat exercise-induced gastrointestinal symptoms. Int J Sport Nutr Exerc Metab. 2016;24:1-17.
131. Gibson PR. The evidence base for efficacy of the low FODMAP diet in irritable bowel syndrome: is it ready for prime time as a first-line therapy? J Gastroenterol Hepatol. 2017;32(suppl 1):32-35.
132. Warden SJ. Prophylactic use of NSAIDs by athletes: a risk/benefit assessment. Phys Sportsmed. 2010;38:132-138.
133. Lambert GP, Boylan M, Laventure JP, Bull A, Lanspa S. Effect of aspirin and ibuprofen on GI permeability during exercise. Int J Sports Med. 2007;28:722-726.
134. Ryan AJ, Chang RT, Gisolfi CV. Gastrointestinal permeability following aspirin intake and prolonged running. Med Sci Sports Exerc. 1996;28:698-705.
135. Buchman AL, O'Brien W, Ou CN, et al. The effect of arginine or glycine supplementation on gastrointestinal function, muscle injury, serum amino acid concentrations and performance during a marathon run. Int J Sports Med. 1999;20:315-321.
136. van Wijck K, Wijnands KA, Meesters DM, et al. L-citrulline improves splanchnic perfusion and reduces gut injury during exercise. Med Sci Sports Exerc. 2014;46:2039-2046.
137. Marchbank T, Davison G, Oakes JR, et al. The nutriceutical bovine colostrum truncates the increase in gut permeability caused by heavy exercise in athletes. Am J Physiol Gastrointest Liver Physiol. 2011;300:G477-G484.
138. Buckley JD, Butler RN, Southcott E, Brinkworth GD. Bovine colostrum supplementation during running training increases intestinal permeability. Nutrients. 2009;1:224-234.
139. Carol A, Witkamp RF, Wichers HJ, Mensink M. Bovine colostrum supplementation's lack of effect on immune variables during short-term intense exercise in well-trained athletes. Int J Sport Nutr Exerc Metab. 2011;21:135-145.
140. Davison G, Marchbank T, March DS, Thatcher R, Playford RJ. Zinc carnosine works with bovine colostrum in truncating heavy exercise-induced increase in gut permeability in healthy volunteers. Am J Clin Nutr. 2016;104:526-536.
141. Lamprecht M, Bogner S, Schippinger G, et al. Probiotic supplementation affects markers of intestinal barrier, oxidation, and inflammation in trained men; a randomized, double-blinded, placebo-controlled trial. J Int Soc Sports Nutr. 2012;9:45.