Abstract
Purpose
The study aimed to determine the effects of exertional-heat stress on gastrointestinal integrity, symptoms, systemic endotoxin and inflammatory responses; and assess the relationship between changes in body temperature and gastrointestinal perturbations.
Methods
Ten endurance runners completed 2 h running at 60% \(\dot {V}\)O2max in hot (HOT: 35 °C) and temperate (TEMP: 22 °C)-ambient conditions. Rectal temperature (T re) and gastrointestinal symptoms were recorded every 10 min during exercise. Blood samples were collected pre- and post-exercise, and during recovery to determine plasma intestinal fatty acid binding protein (I-FABP), cortisol, bacterial endotoxin and cytokine profile. Calprotectin was determined from pre- and post-exercise faecal samples. Urinary lactulose:l-rhamnose ratio was used to measure intestinal permeability.
Results
Compared with TEMP, HOT significantly increased T re (1.4 ± 0.5 vs 2.4 ± 0.8 °C, p < 0.001), cortisol (26 vs 82%, p < 0.001), I-FABP (127 vs 432%, p < 0.001), incidence (70 vs 90%) and severity (58 counts vs 720 counts, p = 0.008) of total gastrointestinal symptoms. Faecal calprotectin and circulating endotoxin increased post-exercise in both trials (mean increase 1.5 ± 2.5 µg/g, p = 0.032, and 6.9 ± 10.3 pg/ml, p = 0.047, respectively), while anti-endotoxin antibodies increased 28% post-exercise in TEMP and decreased 21% in HOT (p = 0.027). However, intestinal permeability did not differ between trials (p = 0.185). Inflammatory cytokines were greater on HOT compared to TEMP (p < 0.05). Increases in T re were positively associated with I-FABP, IL-10, cortisol, nausea and urge to regurgitate (p < 0.05).
Conclusions
Exertional-heat stress induces a thermoregulatory strain that subsequently injures the intestinal epithelium, reduces endotoxin clearance capacity, promotes greater cytokinaemia, and development of gastrointestinal symptoms.
Similar content being viewed by others
Abbreviations
- ANOVA:
-
Analysis of variance
- CI:
-
Confidence interval
- CV:
-
Coefficient of variation
- ELISA:
-
Enzyme-linked immunosorbent assay
- FODMAP:
-
Fermentable oligosaccharides, disaccharides, monosaccharides and polyols
- HOT:
-
Hot conditions (35 °C ambient temperature).
- IL-1β:
-
Interleukin 1 beta
- IL-1ra:
-
Interleukin 1 receptor antagonist
- IL-6:
-
Interleukin 6
- IL-8:
-
Interleukin 8
- IL-10:
-
Interleukin 10
- I-FABP:
-
Intestinal fatty acid binding protein
- RPE:
-
Rating of perceived exertion
- SD:
-
Standard deviation
- SEM:
-
Standard error of the mean
- TEMP:
-
Temperate conditions (22 °C ambient temperature).
- TNF-α:
-
Tumor necrosis factor alpha
- T re :
-
Rectal temperature
- \(\dot {V}\)O2max :
-
Maximal oxygen uptake
- W max :
-
Maximum workload
References
Barberio MD, Elmer DJ, Laird RH, Lee KA, Gladden B, Pascoe DD (2015) Systemic LPS and inflammatory response during consecutive days of exercise in heat. Int J Sports Med 36(3):262–270
Bengtsson M, Persson J, Sjölund K, Ohlsson B (2013) Further validation of the visual analogue scale for irritable bowel syndrome after use in clinical practice. Gastroenterol Nurs 36(3):188–198
Bjarnason I, MacPherson A, Hollander D (1995) Intestinal permeability: an overview. Gastroenterol 108(5):1566–1581
Borg GA (1982) Psychophysical bases of perceived exertion. Med Sci Sports Exerc 14(5):377 – 81
Bressler B, Panaccione R, Fedorak RN, Seidman EG (2015) Clinicians’ guide to the use of fecal calprotectin to identify and monitor disease activity in inflammatory bowel disease. Can J Gastroenterol Hepatol 29(7):369–372
Brock-Utne JG, Gaffin SL, Wells MT, Gathiram P, Sohar E, James MF et al (1988) Endotoxaemia in exhausted runners after a long-distance race. S Afr Med J 73(9):533–536
Camus G, Nys M, Poortmans JR, Venneman I, Monfils T, Deby-Dupont G et al (1998) Endotoxaemia, production of tumour necrosis factor α and polymorphonuclear neutrophil activation following strenuous exercise in humans. Eur J Appl Physiol Occup Physiol 79(1):62–68
Caradonna L, Amati L, Magrone T, Pellegrino NM, Jirillo E, Caccavo D (2000) Enteric bacteria, lipopolysaccharides and related cytokines in inflammatory bowel disease: biological and clinical significance. J Endotoxin Res 6(32):205–214
Choi SC, Choi SJ, Kim JA, Kim TH, Nah YH, Yazaki E et al (2001) The role of gastrointestinal endoscopy in long-distance runners with gastrointestinal symptoms. Eur J Gastroenterol Hepatol 13(9):1089–1094
Cohen DC, Winstanley A, Engledow A, Windsor AC, Skipworth JR (2009) Marathon-induced ischemic colitis: why running is not always good for you. Am J Emerg Med 27(2):255.e5–255.e7
Colgan SP, Taylor CT (2010) Hypoxia: an alarm signal during intestinal inflammation. Nat Rev Gastroenterol Hepatol 7(5):281–287
Costa RJ, Snipe R, Camões-Costa V, Scheer V, Murray A (2016) The impact of gastrointestinal symptoms and dermatological injuries on nutritional intake and hydration status during ultramarathon events. Sports Med Open 2:16
Costa RJS, Miall A, Khoo A, Rauch C, Snipe R, Camões-Costa V et al (2017a) Gut-training: the impact of two weeks repetitive gut-challenge during exercise on gastrointestinal status, glucose availability, fuel kinetics, and running performance. Appl Physiol Nutr Metab 42(5):547–557
Costa RJS, Snipe RMJ, Kitic CM, Gibson PR (2017b) Systematic review: exercise-induced gastrointestinal syndrome-implications for health and intestinal disease. Aliment Pharmacol Ther 46(3):246–265
Dokladny K, Moseley PL, Ma TY (2006) Physiologically relevant increase in temperature causes an increase in intestinal epithelial tight junction permeability. Am J Physiol Gastrointest Liver Physiol 290(2):G204–G212
Gill SK, Hankey J, Wright A, Marczak S, Hemming K, Allerton DM et al (2015a) The impact of a 24-h ultra-marathon on circulatory endotoxin and cytokine profile. Int J Sports Med 36(8):688–695
Gill SK, Teixeira A, Rama L, Prestes J, Rosado F, Hankey J et al (2015b) Circulatory endotoxin concentration and cytokine profile in response to exertional-heat stress during a multi-stage ultra-marathon competition. Exerc Immunol Rev 21:114–128
Gill SK, Allerton DM, Ansley-Robson P, Hemmings K, Cox M, Costa RJ (2016) Does short-term high dose probiotic supplementation containing lactobacillus casei attenuate exertional-heat stress induced endotoxaemia and cytokinaemia?. Int J Sport Nutr Exerc Metab 26(3):268–275
Grootjans J, Lenaerts K, Buurman WA, Dejong CHC, Derikx JPM (2016) Life and death at the mucosal-luminal interface: new perspectives on human intestinal ischemia-reperfusion. World J Gastroenterol 22(9):2760–2770
Hall DM, Buettner GR, Oberley LW, Xu L, Matthes RD, Gisolfi CV (2001) Mechanisms of circulatory and intestinal barrier dysfunction during whole body hyperthermia. Am J Physiol Heart Circ Physiol 280(2):H509–H521
Hoffman MD, Fogard K (2011) Factors related to successful completion of a 161-km ultramarathon. Int J Sports Physiol Perform 6(1):25–37
Hollies NRS, Goldman RF (1977) Psychological scaling in comfort assessment. In: Hollies NRS, Goldman RF (eds.) Clothing comfort: Interaction of thermal, ventilation, construction, and assessment factors. Ann Arbor Science Publishers Inc. Michigan, USA, pp 107–20
Horner KM, Schubert MM, Desbrow B, Byrne NM, King NA (2015) Acute exercise and gastric emptying: a meta-analysis and implications for appetite control. Sports Med 45(5):659–678
Ikari A, Nakano M, Suketa Y, Harada H, Takagi K (2005) Reorganization of ZO-1 by sodium-dependent glucose transporter activation after heat stress in LLC-PK1 cells. J Cell Physiol 203(3):471–478
Jeukendrup AE, Vet-Joop K, Sturk A, Stegen JH, Senden J, Saris WH et al (2000) 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 (Lond) 98(1):47–55
Kaparakis-Liaskos M, Ferrero RL (2015) Immune modulation by bacterial outer membrane vesicles 2015. Nat Rev Immunol 15:375–387
Kenney WL, Ho CW (1995) Age alters regional distribution of blood flow during moderate-intensity exercise. J Appl Physiol 79(4):1112–1119
Lambert CP, Lang J, Bull A, Eckerson J, Lanspa S, O’Brien J (2008a) Fluid tolerance while running: effect of repeated trials. Int J Sports Med 29(11):878–882
Lambert CP, Lang J, Bull A, Pfeifer PC, Eckerson J, Moore C et al (2008b) Fluid restriction during running increases GI permeability. Int J Sports Med 29(3):194–198
Lang JA, Gisolfi CV, Lambert GP (2006) Effect of exercise intensity on active and passive glucose absorption. Int J Sport Nutr Exerc Metab 16(5):485–493
Leiper JB (2015) Fate of ingested fluids: factors affecting gastric emptying and intestinal absorption of beverages in humans. Nutr Rev 73(Suppl 2):57–72
Lim CL, Mackinnon LT (2006) The roles of exercise-induced immune system disturbances in the pathology of heat stroke: the dual pathway model of heat stroke. Sports Med 36(1):39–64
Lim CL, Pyne D, Horn P, Kalz A, Sauders P, Peake J et al (2009) The effects of increased endurance training load on biomarkers of heat intolerance during intense exercise in the heat. Appl Physiol Nutr Metab 34(4):616–624
Lis D, Stellingwerff T, Kitic CM, Ahuja KDK, Fell J (2015) No effects of a short-term gluten-free diet on performance in nonceliac athletes. Med Sci Sports Exerc 47(12):2563–2570
Lis D, Ahuja KD, Stellingwerff T, Kitic CM, Fell J (2016a) Food avoidance in athletes: FODMAP foods on the list. Appl Physiol Nutr Metab 41(9):1002–1004
Lis D, Ahuja KD, Stellingwerff T, Kitic CM, Fell J (2016b) Case Study: utilizing a low FODMAP diet to combat exercise-induced gastrointestinal symptoms. Int J Sport Nutr Exerc Metab 26(5):481–487
Morris G, Berk M, Galecki P, Maes M (2014) The emerging role of autoimmunity in myalgic encephalomyelitis/chronic fatigue syndrome (ME/cfs). Mol Neurobiol 49(2):741–756
Morrison SA, Cheung SS, Cotter JD (2014) Bovine colostrum, training status, and gastrointestinal permeability during exercise in the heat: a placebo-controlled double-blind study. Appl Physiol Nutr Metab 39(9):1070–1082
Neufer PD, Young AJ, Sawka MN (1989) Gastric emptying during exercise: effects of heat stress and hypohydration. Eur J Appl Physiol Occup Physiol 58(4):433–439
Oliver SR, Phillips NA, Novosad VL, Bakos MP, Talbert EE, Clanton TL (2012) Hyperthermia induces injury to the intestinal mucosa in the mouse: evidence for an oxidative stress mechanism. Am J Physiol Regul Integr Comp Physiol 302(7):R845–R853
Pals KL, Chang RT, Ryan AJ, Gisolfi CV (1997) Effect of running intensity on intestinal permeability. J Appl Physiol 82(2):571–576
Pires W, Veneroso CE, Wanner SP, Pacheco DA, Vaz GC, Amorim FT et al (2016) Association between exercise-induced hyperthermia and intestinal permeability: a systematic review. Sports Med 47(7):1389–1403
Pous-Serrano S, Frasson M, Cerrillo E, Beltrán B, Iborra M, Hervás D et al (2017) Correlation between fecal calprotectin and inflammation in the surgical specimen of Crohn’s disease. J Surg Res 213:290–297
Pugh JN, Impey SG, Doran DA, Fleming SC, Morton JP, Close GL (2017) Acute high-intensity interval running increases markers of gastrointestinal damage and permeability but not gastrointestinal symptoms. Appl Physiol Nutr Metab 16:1–7
Rav-Acha M, Hadad E, Epstein Y, Heled Y, Moran DS (2004) Fatal exertional heat stroke: a case series. Am J Med Sci 328(2):84–87
Rehrer NJ, van Kemenade M, Meester W, Brouns F, Saris WH (1992) Gastrointestinal complaints in relation to dietary intake in triathletes. Int J Sport Nutr 2(1):48–59
Rehrer NJ, Smets A, Reynaert H, Goes E, De Meirleir K (2001) Effect of exercise on portal vein blood flow in man. Med Sci Sports Exerc 33(9):1533–1537
Robson P (2003) Elucidating the unexplained underperformance syndrome in endurance athletes: the interleukin-6 hypothesis. Sports Med 10:771–781
Sanchez LD, Tracy JA, Berkoff D, Pedrosa I (2006) Ischemic colitis in marathon runners: a case-based review. J Emerg Med 30(3):321–326
Selkirk GA, McLellan TM, Wright HE, Rhind SG (2008) Mild endotoxemia, NF-kappaB translocation, and cytokine increase during exertional heat stress in trained and untrained individuals. Am J Physiol Regul Integr Comp Physiol 295(2):R611–R623
Sessions J, Bourbeau K, Rosinski M, Szczygiel T, Nelson R, Sharma N et al (2016) Carbohydrate gel ingestion during running in the heat on markers of gastrointestinal distress. Eur J Sport Sci 16(8):1064–1072
Shah B, Sullivan CJ, Lonergan NE, Stanley S, Soult MC, Britt LD (2012) Circulating bacterial membrane vesicles cause sepsis in rats. Shock 37(6):621–628
Starkie RL, Hargreaves M, Rolland J, Febbraio MA (2005) Heat stress, cytokines, and the immune response to exercise. Brain Behav Immun 19(5):404–412
Steensberg A, Fischer CP, Keller C, Moller K, Pedersen BK (2003) IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans. Am J Physiol Endocrinol Metab 285(2):E433–E437
Stuempfle KJ, Hoffman MD (2015) Gastrointestinal distress is common during a 161-km ultramarathon. J Sports Sci 33(17):1814–1821
Stuempfle KJ, Hoffman MD, Hew-Butler T (2013) Association of gastrointestinal distress in ultramarathoners with race diet. Int J Sport Nutr Exerc Metab 23(2):103–109
ter Steege RW, Kolkman JJ (2012) The pathophysiology and management of gastrointestinal symptoms during physical exercise, and the role of splanchnic blood flow. Aliment Pharmacol Ther 35:516–528
Tuck CJ, Ross LA, Gibson PR, Barrett JS, Muir JG (2017) Adding glucose to food and solutions to enahance fructose absorption is not effective in prevneting fructose induced functional gastrointestinal symptoms: randomised controlled trials in patients with fructose malabsorption. J Hum Nutr Diet 30:73–82
van Nieuwenhoven MA, Brouns F, Brummer RJM (1999) The effect of physical exercise on parameters of gastrointestinal function. Neurogastroenterol Motil 11(6):431–439
van Nieuwenhoven MA, Brouns F, Brummer R (2004) Gastrointestinal profile of symptomatic athletes at rest and during physical exercise. Eur J Appl Physiol 91:429–434
van Wijck K, Lenaerts K, van Loon LJC, Peters WHM, Buurman WA, Dejong CHC (2011) Exercise-Induced splanchnic hypoperfusion results in gut dysfunction in healthy men. PLoS One 6(7):e22366
van Wijck K, Lenaerts K, Grootjans J, Wijnands KAP, Poeze M, van Loon LJC et al (2012a) Physiology and pathophysiology of splanchnic hypoperfusion and intestinal injury during exercise: strategies for evaluation and prevention. Am J Physiol Gastrointest Liver Physiol 303(2):G155–G68
van Wijck K, Lenaerts K, Van Bijnen AA, Boonen B, van Loon LJC, Dejong CH (2012b) Aggravation of exercise-induced intestinal injury by ibuprofen in athletes. Med Sci Sports Exerc 44(12):2257–2262
van Wijck K, Pennings B, van Bijnen AA, Senden JM, Buurman WA, Dejong CH et al (2013) Dietary protein digestion and absorption are impaired during acute postexercise recovery in young men. Am J Physiol Regul Integr Comp Physiol 304(5):R356–R361
van Wijck K, Wijnands KA, Meesters DM, Boonen B, van Loon LJ, Buurman WA et al (2014) L-citrulline improves splanchnic perfusion and reduces gut injury during exercise. Med Sci Sports Exerc 46(11):2039–2046
Wendt D, van Loon LJ, Lichtenbelt WD (2007) Thermoregulation during exercise in the heat: strategies for maintaining health and performance. Sports Med 37(8):669–682
Wittkopf N, Neurath MF, Becker C (2014) Immune-epithelial crosstalk at the intestinal surface. J Gastroenterol 49(3):375–387
Yeh Y, Law L, Lim C (2013) Gastrointestinal response and endotoxemia during intense exercise in hot and cool environments. Eur J Appl Physiol 113(6):1575–1583
Zuhl M, Schneider S, Lanphere K, Conn C, Dokladny K, Moseley P (2014) Exercise regulation of intestinal tight junction proteins. Br J Sports Med 48(12):1–9
Zuhl M, Dokladny K, Mermier C, Schneider S, Salgado R, Moseley P (2015) 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 20(1):85–93
Acknowledgements
First, the authors would like to thank all the participants that volunteered to take part in this study. The authors’ contributions are as follows: Ricardo Costa (RC) was the chief investigator of this research. RC, Rhiannon Snipe (RS), and Peter Gibson (PG) contributed towards the original research idea and development of the experimental design. RC, RS, Anthony Khoo (AK), and Cecilia Kitic (CK) contributed to the various aspects of data collection, and sample collection and analysis. RC and RS contributed to the analysis of the raw data. All authors contributed to the preparation and review of the manuscript. All authors read and approved the final manuscript. The study was supported by the ‘Monash University, Faculty of Medicine Nursing and Health Sciences Strategic Grant Scheme’.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
PG has served as consultant or advisory board member for AbbVie, Ferring, Janssen, Merck, Nestle Health Science, Danone, Allergan, Pfizer, Celtrion and Takeda. His institution has received speaking honoraria from AbbVie, Janssen, Ferring, Takeda, Fresenius Kabi, Mylan and Pfizer. He has received research Grants for investigator-driven studies from AbbVie, Janssen, Falk Pharma, Danone and A2 Milk Company. His Department financially benefits from the sales of a digital application and booklets on the low FODMAP diet. Other authors have nothing to declare.
Additional information
Communicated by Narihiko Kondo.
Rights and permissions
About this article
Cite this article
Snipe, R.M.J., Khoo, A., Kitic, C.M. et al. The impact of exertional-heat stress on gastrointestinal integrity, gastrointestinal symptoms, systemic endotoxin and cytokine profile. Eur J Appl Physiol 118, 389–400 (2018). https://doi.org/10.1007/s00421-017-3781-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00421-017-3781-z