Exercise-Induced Splanchnic Hypoperfusion Results in Gut Dysfunction in Healthy Men
Open accessAbstract
BACKGROUND: Splanchnic hypoperfusion is common in various pathophysiological conditions and often considered to lead to gut dysfunction. While it is known that physiological situations such as physical exercise also result in splanchnic hypoperfusion, the consequences of flow redistribution at the expense of abdominal organs remained to be determined. This study focuses on the effects of splanchnic hypoperfusion on the gut, and the relationship between hypoperfusion, intestinal injury and permeability during physical exercise in healthy men. METHODS AND FINDINGS: Healthy men cycled for 60 minutes at 70% of maximum workload capacity. Splanchnic hypoperfusion was assessed using gastric tonometry. Blood, sampled every 10 minutes, was analyzed for enterocyte damage parameters (intestinal fatty acid binding protein (I-FABP) and ileal bile acid binding protein (I-BABP)). Changes in intestinal permeability were assessed using sugar probes. Furthermore, liver and renal parameters were assessed. Splanchnic perfusion rapidly decreased during exercise, reflected by increased gap(g-a)pCO(2) from -0.85±0.15 to 0.85±0.42 kPa (p<0.001). Hypoperfusion increased plasma I-FABP (615±118 vs. 309±46 pg/ml, p<0.001) and I-BABP (14.30±2.20 vs. 5.06±1.27 ng/ml, p<0.001), and hypoperfusion correlated significantly with this small intestinal damage (r(S) = 0.59; p<0.001). Last of all, plasma analysis revealed an increase in small intestinal permeability after exercise (p<0.001), which correlated with intestinal injury (r(S) = 0.50; p<0.001). Liver parameters, but not renal parameters were elevated. CONCLUSIONS: Exercise-induced splanchnic hypoperfusion results in quantifiable small intestinal injury. Importantly, the extent of intestinal injury correlates with transiently increased small intestinal permeability, indicating gut barrier dysfunction in healthy individuals. These physiological observations increase our knowledge of splanchnic hypoperfusion sequelae, and may help to understand and prevent these phenomena in patients.
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Exercise-induced redistribution of blood can result in splanchnic hypoperfusion as a possible mechanism for gut dysfunction.
“Exercise-induced redistribution of blood can result in splanchnic hypoperfusion as a possible mechanism for gut dysfunction [128, 129].”
From International Society of Sports Nutrition Position Stand: Probiotics (2019) · cites this paper as [129]
Symptoms such as nausea, cramping, bloating, and diarrhea most likely reflect redistribution of blood flow from the gut to the skin for cooling purposes.
“Symptoms such as nausea, cramping, bloating, and diarrhea most likely reflect redistribution of blood flow from the gut to the skin for cooling purposes.”
From International Society of Sports Nutrition Position Stand: Probiotics (2019) · cites this paper as [129]
Exercise-induced GI hypoperfusion may provoke transient damage to the gut epithelium.
“It has been shown that exercise induced GI hypoperfusion may provoke transient damage to the gut epithelium [6]”
GI distress during ultra-marathon is likely the result of reduced mesenteric blood flow leading to relative GI hypoperfusion.
“The pathophysiology of GI distress during ultra-marathon training and racing is multifactorial, but is likely the result of reduced mesenteric blood flow [131, 132], leading to relative GI hypoperfusion [133].”
From International Society of Sports Nutrition Position Stand: nutritional considerations for single-stage ultra-marathon training and racing (2019) · cites this paper as [133]
The pathophysiology of GI distress during ultra-marathon training and racing is multifactorial.
“The pathophysiology of GI distress during ultra-marathon training and racing is multifactorial, but is likely the result of reduced mesenteric blood flow [131, 132], leading to relative GI hypoperfusion [133].”
From International Society of Sports Nutrition Position Stand: nutritional considerations for single-stage ultra-marathon training and racing (2019) · cites this paper as [133]
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Cites
Muscle as an Endocrine Organ: Focus on Muscle-Derived Interleukin-6
Pedersen, B. K., & Febbraio, M. A. (2008) · Physiological Reviews · doi:10.1152/physrev.90100.2007 · Cited by 2,388 · cited 1× · see citing works
“Since evidence is accumulating that inflammatory products are produced in contracting and skeletal muscle [32,45], we determined both circulating and faecal calprotectin.”
BackgroundVogl, T., Tenbrock, K., Ludwig, S., Leukert, N., Ehrhardt, C., van Zoelen, M. A. D., Nacken, W., Foell, D., van der Poll, T., Sorg, C., et al. (2007) · Nature Medicine · doi:10.1038/nm1638 · Cited by 1,418 · cited 1× · see citing works
“MPO plays a role in oxidative processes, while calprotectin and one of its constituents, myeloid-related protein-8 (Mrp8, S100A8), are identified as strong activators of the innate Toll-like receptor 4 signaling pathway, resulting in the expression of pro-inflammatory cytokines [30].”
BackgroundEvaluation of Abnormal Liver-Enzyme Results in Asymptomatic Patients
Pratt, D. S., & Kaplan, M. M. (2000) · New England Journal of Medicine · doi:10.1056/nejm200004273421707 · Cited by 1,203 · cited 1× · see citing works
“Alternatively, muscle transaminase release is expected in response to (exerciseinduced) muscle injury [23,24], while L-FABP release could be due to intestinal damage.”
BackgroundAltered intestinal function in patients with chronic heart failure
Sandek, A., Bauditz, J., Swidsinski, A., Buhner, S., Weber-Eibel, J., von Haehling, S., Schroedl, W., Karhausen, T., Doehner, W., Rauchhaus, M., et al. (2007) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2007.07.016 · Cited by 661 · cited 1× · see citing works
“In patients with compromised vascular function, hypoperfusion-induced epithelial dysfunction may give rise to endotoxaemia, thereby enhancing their state of chronic inflammation, as suggested by the group of Anker for patients with chronic heart failure [6,37].”
BackgroundRestoration of Barrier Function in Injured Intestinal Mucosa
Blikslager, A. T., Moeser, A. J., Gookin, J. L., Jones, S. L., & Odle, J. (2007) · Physiological Reviews · doi:10.1152/physrev.00012.2006 · Cited by 573 · cited 1× · see citing works
“The susceptibility of the mature enterocyte population to low-flow states and ischemic events has been explained by the counter current exchange mechanism in the villus [18,19], creating a constant low oxygen environment at the villus tip.”
BackgroundLiangos, O., Perianayagam, M. C., Vaidya, V. S., Han, W. K., Wald, R., Tighiouart, H., MacKinnon, R. W., Li, L., Balakrishnan, V. S., Pereira, B. J. G., et al. (2007) · Journal of the American Society of Nephrology · doi:10.1681/asn.2006030221 · Cited by 511 · see citing works
A simple method for assessing intestinal inflammation in Crohn's disease
Tibble, J. A., Teahon, K., Thjodleifsson, B., Roseth, A., Sigthorsson, G., Bridger, S., Foster, R., Sherwood, R. A., Fagerhol, M. K., & Bjarnason, I. (2000) · Gut · doi:10.1136/gut.47.4.506 · Cited by 493 · cited 1× · see citing works
“The latter is considered a strong indicator of intestinal inflammation in specific, and has been found to correlate to other parameters of intestinal inflammation in inflammatory bowel disease [46] and enteropathy induced by non-steroidal anti-inflammatory drugs (NSAID) [47].”
BackgroundFatty acid-binding proteins as plasma markers of tissue injury
Pelsers, M. M. A. L., Hermens, W. T., & Glatz, J. F. C. (2004) · Clinica Chimica Acta · doi:10.1016/j.cccn.2004.09.001 · Cited by 488 · cited 1× · see citing works
“However, as expression of L-FABP has been described in renal and intestinal epithelium [40], this marker was combined with the classically used parameters ALT and AST.”
MethodThermoregulatory and blood responses during exercise at graded hypohydration levels
Sawka, M. N., Young, A. J., Francesconi, R. P., Muza, S. R., & PANDOLF, K. B. (1985) · Journal of Applied Physiology · doi:10.1152/jappl.1985.59.5.1394 · Cited by 402 · cited 1× · see citing works
“transpiration and inadequate fluid intake, can decrease cardiac output and compromise splanchnic perfusion even more [9].”
BackgroundSerum alanine aminotransferase in skeletal muscle diseases†
Nathwani, R. A., Pais, S. A., Reynolds, T. B., & Kaplowitz, N. (2005) · Hepatology · doi:10.1002/hep.20548 · Cited by 400 · cited 1× · see citing works
“Alternatively, muscle transaminase release is expected in response to (exerciseinduced) muscle injury [23,24], while L-FABP release could be due to intestinal damage.”
BackgroundGiglio, M., Marucci, M., Testini, M., & Brienza, N. (2009) · British Journal of Anaesthesia · doi:10.1093/bja/aep279 · Cited by 372 · cited 1× · see citing works
“. In addition, gastrointestinal (GI) dysfunction is one of the more frequent complications in surgical patients, in whom organ perfusion and oxygen delivery are often impaired as a consequence of surgery-induced alterations in cardio-respiratory and metabolic demands”
BackgroundJEUKENDRUP, A. E., VET-JOOP, K., STURK, A., STEGEN, J. H. J. C., SENDEN, J., SARIS, W. H. M., & WAGENMAKERS, A. J. M. (2000) · Clinical Science · doi:10.1042/cs0980047 · Cited by 371 · cited 1× · see citing works
“found mild endotoxaemia (5–15 pg/ml) and increased levels of C-reactive protein in the majority of participants after finishing an approximately 12 h long-distance triathlon [33].”
BackgroundMyeloperoxidase in kidney disease
Malle, E., Buch, T., & Gröne, H. (2003) · Kidney International · doi:10.1046/j.1523-1755.2003.00336.x · Cited by 350 · cited 1× · see citing works
“Active MPO is known to elicit secretion of other cytokines including tumor necrosis factor-a and interleukins [44], which were therefore less useful.”
BackgroundKavouras, S. A. (2002) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/00075197-200209000-00010 · Cited by 323 · cited 1× · see citing works
“The increases, however, largely exceeded the 10% decrease in plasma volume that has been described in athletes in more extreme settings than ours [22].”
High prevalence of NSAID enteropathy as shown by a simple faecal test
Tibble, J. A., Sigthorsson, G., Foster, R., Scott, D. L., Fagerhol, M. K., Røseth, A. G., & Bjarnason, I. (1999) · Gut · doi:10.1136/gut.45.3.362 · Cited by 308 · cited 1× · see citing works
“The latter is considered a strong indicator of intestinal inflammation in specific, and has been found to correlate to other parameters of intestinal inflammation in inflammatory bowel disease [46] and enteropathy induced by non-steroidal anti-inflammatory drugs (NSAID) [47].”
BackgroundEffects of exercise on mesenteric blood flow in man.
Qamar, M. I., & Read, A. E. (1987) · Gut · doi:10.1136/gut.28.5.583 · Cited by 234 · cited 2× · see citing works
“During physical exercise, reduction of the splanchnic circulation occurs to meet the increased demand for oxygen and substrates in the active muscle, thereby inducing a physiological state of hypoperfusion in the GI system [8].”
BackgroundPeters, H. P. F., Bos, M., Seebregts, L., Akkermans, L. M. A., van Berge Henegouwen, G. P., Bol, E., Mosterd, W. L., & de Vries, W. R. (1999) · American Journal of Gastroenterology · doi:10.1111/j.1572-0241.1999.01147.x · Cited by 188 · cited 1× · see citing works
“Especially during prolonged running or cycling, athletes can experience abdominal symptoms such as cramping, nausea, abdominal pain, and (bloody) diarrhea [10].”
BackgroundHuman Intestinal Ischemia-Reperfusion–Induced Inflammation Characterized
Grootjans, J., Lenaerts, K., Derikx, J. P. M., Matthijsen, R. A., de Bruïne, A. P., van Bijnen, A. A., van Dam, R. M., Dejong, C. H. C., & Buurman, W. A. (2010) · The American Journal of Pathology · doi:10.2353/ajpath.2010.091069 · Cited by 186 · see citing works
Self-citationMurray, C. D. R., Flynn, J., Ratcliffe, L., Jacyna, M. R., Kamm, M. A., & Emmanuel, A. V. (2004) · Gastroenterology · doi:10.1053/j.gastro.2004.08.057 · Cited by 185 · cited 1× · see citing works
“that found a decrease in rectal mucosal blood flow of almost 30% after acute physical stress [34], while decreases ranging from 43 to approximately 80% have been reported for splanchnic blood flow during physical exercise [8,35].”
BackgroundPhysical exercise increases portal pressure in patients with cirrhosis and portal hypertension
García‐Pagán, J. C., Santos, C., Barberà, J. A., Luca, A., Roca, J., Rodriguez‐Roisin, R., Bosch, J., & Rodés, J. (1996) · Gastroenterology · doi:10.1053/gast.1996.v111.pm8898644 · Cited by 176 · cited 1× · see citing works
“. In short, the significant rise in the assessed liver parameters after exercise strongly suggests the development of mild hepatocyte damage, which is in line with Garcia-Pagan et al. who reported a decrease in hepatic blood flow in patients with liver cirrhosis and portal hypertension after only 10 minutes of cycling…”
ResultDiagnosis and management of intestinal ischaemic disorders
Sreenarasimhaiah, J. (2003) · BMJ · doi:10.1136/bmj.326.7403.1372 · Cited by 162 · cited 1× · see citing works
“Splanchnic hypoperfusion occurs in many pathophysiological conditions, and is often considered to lead to epithelial barrier dysfunction. Vascular disease, trauma, and shock can induce splanchnic hypoperfusion and ischemia”
BackgroundMesenteric, coeliac and splanchnic blood flow in humans during exercise
Perko, M. J., Nielsen, H. B., Skak, C., Clemmesen, J. O., Schroeder, T. V., & Secher, N. H. (1998) · The Journal of Physiology · doi:10.1111/j.1469-7793.1998.907ba.x · Cited by 162 · cited 1× · see citing works
“Previous studies support the former, showing relatively unchanged renal flow after short-term splanchnic blood redistribution [28,29].”
ResultGastrointestinal Complications in Patients Undergoing Heart Operation
Mangi, A. A., Christison-Lagay, E. R., Torchiana, D. F., Warshaw, A. L., & Berger, D. L. (2005) · Annals of Surgery · doi:10.1097/01.sla.0000164173.05762.32 · Cited by 158 · see citing works
EVIDENCE FOR INTESTINAL AND LIVER EPITHELIAL CELL INJURY IN THE EARLY PHASE OF SEPSIS
Derikx, J. P. M., Poeze, M., van Bijnen, A. A. J. H. M., Buurman, W. A., & Heineman, E. (2007) · Shock · doi:10.1097/shk.0b013e3180644e32 · Cited by 138 · see citing works
Self-citationExercise induces gastric ischemia in healthy volunteers: a tonometry study
Otte, J. A., Oostveen, E., Geelkerken, R. H., Groeneveld, A. B. J., & Kolkman, J. J. (2001) · Journal of Applied Physiology · doi:10.1152/jappl.2001.91.2.866 · Cited by 138 · cited 1× · see citing works
“hypoperfusion during strenuous physical exercise [5], whereas older individuals may experience similar events during less”
BackgroundDerikx, J. P. M., Matthijsen, R. A., A, A. P. D. B., van Bijnen, A. A. J. H. M., Heineman, E., van Dam, R. M., Dejong, C. H. C., & Buurman, W. A. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003428 · Cited by 126 · see citing works
Self-citationChanges in the Gastrointestinal Mucosa after Long-Distance Running
Øktedalen, O., Lunde, O. C., Opstad, P. K., Aabakken, L., & Kvernebo, K. (1992) · Scandinavian Journal of Gastroenterology · doi:10.3109/00365529209000073 · Cited by 124 · cited 1× · see citing works
“. This points towards compromised GI functioning, but only few studies have looked at exercise-induced intestinal mucosal lesions in man”
BackgroundDerikx, J. P. M., Vreugdenhil, A. C. E., den Neucker, A. M. V., Grootjans, J., van Bijnen, A. A. J. H. M., Damoiseaux, J. G. M. C., van Heurn, E. L. W., Heineman, E., & Buurman, W. A. (2009) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0b013e31819194b0 · Cited by 123 · cited 1× · see citing works
“I-FABP, a sensitive marker of intestinal cell damage, was used to determine small intestinal damage [15].”
MethodSelf-citationvan de Poll, M. C. G., Derikx, J. P. M., Buurman, W. A., Peters, W. H. M., Roelofs, H. M. J., Wigmore, S. J., & Dejong, C. H. C. (2007) · World Journal of Surgery · doi:10.1007/s00268-007-9182-4 · Cited by 122 · see citing works
Self-citationKnowles, T. P., Mullin, R., Hunter, J. A., & Douce, F. H. (2006) · Respiratory Care · doi:10.4187/respcare.06510732 · Cited by 112 · cited 1× · see citing works
“To avoid the use of an arterial catheter, an intravenous catheter (22 Gauge, BD) was placed in a dorsal hand vein and the hand was placed in a hot box heated to 60uC, to arterialize the blood for measuring arterial pCO2 [39], using a Radiometer ABL 510 (Copenhagen, Denmark).”
MethodTer Steege, R. W. F., Van Der Palen, J., & Kolkman, J. J. (2008) · Scandinavian Journal of Gastroenterology · doi:10.1080/00365520802321170 · Cited by 111 · see citing works
New Insight in Loss of Gut Barrier during Major Non-Abdominal Surgery
Derikx, J. P. M., van Waardenburg, D. A., Thuijls, G., Willigers, H. M., Koenraads, M., van Bijnen, A. A. J. H. M., Heineman, E., Poeze, M., Ambergen, T., van Ooij, A., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003954 · Cited by 86 · cited 1× · see citing works
“Our observations are in line with recent work on human intestinal ischemia/reperfusion (I/R) studies from our group showing that after 30 minutes of full intestinal ischemia in an isolated part of the jejunum during a Whipple procedure, plasma I-FABP levels rapidly increase, whereas during reperfusion, a gradual decre…”
ResultSelf-citationHolland, J., Carey, M., Hughes, N., Sweeney, K., Byrne, P. J., Healy, M., Ravi, N., & Reynolds, J. V. (2005) · The American Journal of Surgery · doi:10.1016/j.amjsurg.2005.03.038 · Cited by 84 · see citing works
Krack, A., Richartz, B. M., Gastmann, A., Greim, K., Lotze, U., Anker, S. D., & Figulla, H. R. (2004) · European Journal of Heart Failure · doi:10.1016/j.ejheart.2004.03.002 · Cited by 83 · cited 1× · see citing works
“In patients with compromised vascular function, hypoperfusion-induced epithelial dysfunction may give rise to endotoxaemia, thereby enhancing their state of chronic inflammation, as suggested by the group of Anker for patients with chronic heart failure [6,37].”
BackgroundThe role of gastrointestinal endoscopy in long-distance runners with gastrointestinal symptoms
Choi, S. C., Choi, S. J., Kim, J. A., Kim, T. H., Nah, Y.-H., Yazaki, E., & Evans, D. F. (2001) · European Journal of Gastroenterology & Hepatology · doi:10.1097/00042737-200109000-00016 · Cited by 74 · see citing works
Effect of ranitidine on basal and bicarbonate enhanced intragastric PCO2: a tonometric study.
Kolkman, J. J., Groeneveld, A. B. J., & Meuwissen, S. G. M. (1994) · Gut · doi:10.1136/gut.35.6.737 · Cited by 70 · cited 1× · see citing works
“The evening before and 1 hour prior to the experiment, participants ingested 150 mg ranitidine orally (GlaxoSmithKline, Zeist, the Netherlands) to suppress gastric acid production, which interferes with carbon dioxide, thereby affecting tonometry results [38].”
MethodMatthijsen, R. A., Derikx, J. P. M., Kuipers, D., van Dam, R. M., Dejong, C. H. C., & Buurman, W. A. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007045 · Cited by 67 · see citing works
Self-citationNakajima, T., Kurano, M., Hasegawa, T., Takano, H., Iida, H., Yasuda, T., Fukuda, T., Madarame, H., Uno, K., Meguro, K., et al. (2010) · European Journal of Applied Physiology · doi:10.1007/s00421-010-1572-x · Cited by 67 · cited 1× · see citing works
“Circulating myeloperoxidase (MPO) and calprotectin, antimicrobial proteins that are excreted from neutrophils upon activation, are considered early parameters of systemic inflammatory activation [42,43].”
BackgroundCalprotectin is released from human skeletal muscle tissue during exercise
Mortensen, O. H., Andersen, K., Fischer, C. P., Nielsen, A. R., Nielsen, S. J., Akerstrom, T. C. A., Aastrøm, M., Borup, R., & Pedersen, B. K. (2008) · The Journal of Physiology · doi:10.1113/jphysiol.2008.153551 · Cited by 66 · cited 2× · see citing works
“, assessing femoral arterialvenous differences during knee extensor exercise, pointed towards release of calprotectin from muscle tissue during exercise [32].”
BackgroundDerikx, J. P. M., Blijlevens, N. M. A., Donnelly, J. P., Fujii, H., Kanda, T., van Bijnen, A. A. J. H. M., Heineman, E., & Buurman, W. A. (2008) · Annals of Oncology · doi:10.1093/annonc/mdn579 · Cited by 60 · cited 1× · see citing works
“. Plasma I-FABP was determined using an ELISA (Hycult Biotechnology, Uden, the Netherlands; detection window 20–5,000 pg/ml) according to the manufacturer's instructions in samples taken before (t = 0), during (t = 10–50 minutes) and after (t = 60–120 minutes) cycling. Plasma ileal bile acid binding protein (I-BABP),…”
MethodInfluentialSelf-citationRegulation of splanchnic blood flow in man.
Rowell, L. B. (1973) · PubMed · Cited by 46 · see citing works
MULDER, T. P. J., Peters, W. H. M., Court, D. A., & Jansen, J. B. �. �. (1996) · Clinical Chemistry · doi:10.1093/clinchem/42.3.416 · Cited by 44 · cited 1× · see citing works
“Plasma alpha-GST levels were assessed using ELISA, as described previously [41].”
MethodSelf-citationA pilot study on potential new plasma markers for diagnosis of acute appendicitis
Thuijls, G., Derikx, J. P. M., Prakken, F. J., Huisman, B. A. A., van Bijnen, A. A. J. H. M., van Heurn, E. L. W., Buurman, W. A., & Heineman, E. (2010) · The American Journal of Emergency Medicine · doi:10.1016/j.ajem.2009.09.029 · Cited by 39 · cited 1× · see citing works
“Circulating myeloperoxidase (MPO) and calprotectin, antimicrobial proteins that are excreted from neutrophils upon activation, are considered early parameters of systemic inflammatory activation [42,43].”
BackgroundSelf-citationLife in the Gut Without Oxygen: Adaptive Mechanisms and Inflammatory Bowel Disease
Blikslager, A. T. (2008) · Gastroenterology · doi:10.1053/j.gastro.2007.11.049 · Cited by 31 · cited 1× · see citing works
“The susceptibility of the mature enterocyte population to low-flow states and ischemic events has been explained by the counter current exchange mechanism in the villus [18,19], creating a constant low oxygen environment at the villus tip.”
BackgroundEvaluation of an Enzyme-Immunometric Assay for Serum α-Glutathione S-Transferase
Rees, G. W., Trull, A. K., & Doyle, S. (1995) · Annals of Clinical Biochemistry International Journal of Laboratory Medicine · doi:10.1177/000456329503200610 · Cited by 28 · see citing works
Veer, G. V. D. S., van den Hoven, B., Rüssel, M. G., & Bergh, F. A. J. T. M. V. D. (2006) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2006.051 · Cited by 22 · see citing works
Effects of changing liver blood flow by exercise and food on kinetics and dynamics of saruplase*
van Griensven, J. M. T., Burggraaf, K., Gerloff, J., Günzler, W. A., Beier, H., Kroon, R., Huisman, L. G. M., Schoemaker, R. C., Kluft, K., & Cohen, A. F. (1995) · Clinical Pharmacology & Therapeutics · doi:10.1016/0009-9236(95)90206-6 · Cited by 19 · see citing works
Splanchnic Vasoregulation After Major Abdominal Surgery in Pigs
Brügger, L. E., Beldi, G., Beck, M., Porta, F., Bracht, H., Candinas, D., Takala, J. A., & Jakob, S. M. (2010) · World Journal of Surgery · doi:10.1007/s00268-010-0560-y · Cited by 8 · cited 1× · see citing works
“Previous studies support the former, showing relatively unchanged renal flow after short-term splanchnic blood redistribution [28,29].”
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Sorted by citations
Intestinal permeability – a new target for disease prevention and therapy
Bischoff, S. C., Barbara, G., Buurman, W., Ockhuizen, T., Schulzke, J.-D., Serino, M., Tilg, H., Watson, A., & Wells, J. M. (2014) · BMC Gastroenterology · doi:10.1186/s12876-014-0189-7 · Cited by 1,755 · see citing works
“in the course of exercise [242].”
Self-citationMedicine & science in sports & exercise
Walle, J. M. L., Solá, I. B., Castillo, I., & Rodríguez, J. L. T. (1994) · Journal of the American Dietetic Association · doi:10.1016/0002-8223(94)92575-5 · Cited by 1,309 · see citing works
Exerkines in health, resilience and disease
Chow, L. S., Gerszten, R. E., Taylor, J. M., Pedersen, B. K., van Praag, H., Trappe, S., Febbraio, M. A., Galis, Z. S., Gao, Y., Haus, J. M., et al. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-022-00641-2 · Cited by 927 · see citing works
Editor's Choice – Management of the Diseases of Mesenteric Arteries and Veins
Björck, M., Koelemay, M., Acosta, S., Bastos Goncalves, F., Kölbel, T., Kolkman, J. J., Lees, T., Lefevre, J. H., Menyhei, G., Oderich, G., et al. (2017) · European Journal of Vascular and Endovascular Surgery · doi:10.1016/j.ejvs.2017.01.010 · Cited by 658 · see citing works
Mailing, L. J., Allen, J. M., Buford, T. W., Fields, C. J., & Woods, J. A. (2019) · Exercise and Sport Sciences Reviews · doi:10.1249/jes.0000000000000183 · Cited by 521 · see citing works
“Exercise also can reduce intestinal blood flow by more than 50%, with significant gut ischemia occurring within 10 min of high-intensity exercise (69).”
BackgroundCosta, R. J. S., Snipe, R. M. J., Kitic, C. M., & Gibson, P. R. (2017) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.14157 · Cited by 429 · see citing works
“Van Wijck et al.(20) n=6 healthy male participants 60 minutes cycling at 70% Wmax.”
InfluentialBlom, D., Fabbri, C., Connor, E. C., Schiestl, F. P., Klauser, D., Böller, T., Eberl, L., & Weisskopf, L. (2011) · Environmental Microbiology · doi:10.1111/j.1462-2920.2011.02582.x · Cited by 380 · see citing works
Intestinal epithelial barrier function and tight junction proteins with heat and exercise
Dokładny, K., Zuhl, M., & Moseley, P. L. (2015) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00536.2015 · Cited by 328 · see citing works
van Wijck, K., Lenaerts, K., Grootjans, J., Wijnands, K. A. P., Poeze, M., van Loon, L. J. C., Dejong, C. H. C., & Buurman, W. A. (2012) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00066.2012 · Cited by 285 · see citing works
Self-citationInternational Society of Sports Nutrition Position Stand: Probiotics
Jäger, R., Mohr, A. E., Carpenter, K. C., Kerksick, C. M., Purpura, M., Moussa, A., Townsend, J. R., Lamprecht, M., West, N. P., Black, K., et al. (2019) · Journal of the International Society of Sports Nutrition · doi:10.1186/s12970-019-0329-0 · Cited by 277 · see citing works
Voluntary and forced exercise differentially alters the gut microbiome in C57BL/6J mice
Allen, J. M., Berg Miller, M. E., Pence, B. D., Whitlock, K., Nehra, V., Gaskins, H. R., White, B. A., Fryer, J. D., & Woods, J. A. (2015) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01077.2014 · Cited by 266 · see citing works
“, intensity and duration) under which exercise takes place influences its effects on host physiology, especially within the GI tract (24, 47).”
Acute Exercise and Hormones Related to Appetite Regulation: A Meta-Analysis
Schubert, M. M., Sabapathy, S., Leveritt, M., & Desbrow, B. (2014) · Sports Medicine · doi:10.1007/s40279-013-0120-3 · Cited by 249 · see citing works
“One would expect acylated ghrelin suppression to be lesser after running-type exercise because of altered splanchnic blood flow, which inhibits ghrelin secretion [28, 29]; however, research indicates that altered blood flow also occurs after vigorous cycling [65].”
Shing, C. M., Peake, J. M., Lim, C. L., Briskey, D., Walsh, N. P., Fortes, M. B., Ahuja, K. D. K., & Vitetta, L. (2014) · European Journal of Applied Physiology · doi:10.1007/s00421-013-2748-y · Cited by 204 · see citing works
Suzuki, K., Tominaga, T., Ruhee, R. T., & Ma, S. (2020) · Antioxidants · doi:10.3390/antiox9050401 · Cited by 190 · see citing works
“, the increase of myeloperoxidase and calprotectin, which are neutrophil and macrophage activation markers), but not endotoxemia after one hour of cycling exercise [85].”
BackgroundDisturbed Intestinal Integrity in Patients With COPD
Rutten, E. P. A., Lenaerts, K., Buurman, W. A., & Wouters, E. F. �. (2013) · CHEST Journal · doi:10.1378/chest.13-0584 · Cited by 184 · see citing works
Self-citationBrzozowski, B., Mazur-Biały, A., Pajdo, R., Kwiecień, S., Bilski, J., Zwolińska-Wcisło, M., Mach, T., & Brzozowski, T. (2016) · Current Neuropharmacology · doi:10.2174/1570159x14666160404124127 · Cited by 168 · see citing works
O’Sullivan, Ó., Cronin, O., Clarke, S. F., Murphy, E. F., Molloy, M., Shanahan, F., & Cotter, P. D. (2015) · Gut Microbes · doi:10.1080/19490976.2015.1011875 · Cited by 168 · see citing works
“Prolonged intestinal hypo-perfusion impairs mucosal homeostasis and causes enterocyte injury.(34) Intestinal ischemia may result, particularly in the setting of dehydration, manifesting as abdominal cramps, diarrhea or occasionally bloody diarrhea.”
BackgroundExercise regulation of intestinal tight junction proteins
Zuhl, M., Schneider, S., Lanphere, K., Conn, C., Dokladny, K., & Moseley, P. (2014) · British Journal of Sports Medicine · doi:10.1136/bjsports-2012-091585 · Cited by 167 · see citing works
Tiller, N. B., Roberts, J. D., Beasley, L., Chapman, S., Pinto, J. M., Smith, L., Wiffin, M., Russell, M., Sparks, S. A., Duckworth, L., et al. (2019) · Journal of the International Society of Sports Nutrition · doi:10.1186/s12970-019-0312-9 · Cited by 164 · see citing works
Codella, R., Luzi, L., & Terruzzi, I. (2018) · Digestive and Liver Disease · doi:10.1016/j.dld.2017.11.016 · Cited by 158 · see citing works
Costa, R. J. S., Miall, A., Khoo, A., Rauch, C., Snipe, R., Camões-Costa, V., & Gibson, P. (2017) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2016-0453 · Cited by 162 · see citing works
Grootjans, J., Lenaerts, K., Buurman, W. A., Dejong, C. H. C., & Derikx, J. P. M. (2016) · World Journal of Gastroenterology · doi:10.3748/wjg.v22.i9.2760 · Cited by 157 · see citing works
Self-citationMcCormick, A. C., Irmisch, S., Reinecke, A., Boeckler, G. A., VEIT, D., Reichelt, M., Hansson, B. S., Gershenzon, J., Köllner, T. G., & Unsicker, S. B. (2014) · Plant Cell & Environment · doi:10.1111/pce.12287 · Cited by 152 · see citing works
ter Steege, R. W. F., & Kolkman, J. J. (2012) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2011.04980.x · Cited by 145 · see citing works
“strongly suggests that this increased intestinal permeability is related to mucosal damage secondary to GIischaemia.(32)”
BackgroundMethodInfluentialSnipe, R. M. J., Khoo, A., Kitic, C. M., Gibson, P. R., & Costa, R. J. S. (2017) · European Journal of Applied Physiology · doi:10.1007/s00421-017-3781-z · Cited by 144 · see citing works
Probiotics supplementation for athletes – Clinical and physiological effects
Pyne, D. B., West, N. P., Cox, A. J., & Cripps, A. W. (2015) · European Journal of Sport Science · doi:10.1080/17461391.2014.971879 · Cited by 139 · see citing works
Association Between Exercise-Induced Hyperthermia and Intestinal Permeability: A Systematic Review
Pires, W., Veneroso, C. E., Wanner, S. P., Pacheco, D. A. S., Vaz, G. C., Amorim, F. T., Tonoli, C., Soares, D. D., & Coimbra, C. C. (2016) · Sports Medicine · doi:10.1007/s40279-016-0654-2 · Cited by 141 · see citing works
Beyond muscle hypertrophy: why dietary protein is important for endurance athletes
Moore, D. R., Camera, D. M., Areta, J. L., & Hawley, J. A. (2014) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2013-0591 · Cited by 138 · see citing works
Burd, N. A., Beals, J. W., Martinez, I. G., Salvador, A. F., & Skinner, S. K. (2019) · Sports Medicine · doi:10.1007/s40279-018-1009-y · Cited by 127 · see citing works
van Wijck, K., Verlinden, T. J. M., van Eijk, H. M. H., Dekker, J. P., Buurman, W. A., Dejong, C. H. C., & Lenaerts, K. (2012) · Clinical Nutrition · doi:10.1016/j.clnu.2012.06.014 · Cited by 125 · see citing works
Self-citationPiton, G., Belon, F., Cypriani, B., Regnard, J., Puyraveau, M., Manzon, C., Navellou, J.-C., & Capellier, G. (2013) · Critical Care Medicine · doi:10.1097/ccm.0b013e31828c26b5 · Cited by 126 · see citing works
“In healthy adults, small bowel hypoperfusion during submaximal effort was recently shown to cause acute reduction of enterocyte mass (15).”
BackgroundHansson, E., Glaser, J. R., Jakobsson, K., Weiss, I., Wesseling, C., Lucas, R. A. I., LEE, J. K. W., Ekström, U., Wijkström, J., Bodin, T., et al. (2020) · Nutrients · doi:10.3390/nu12061639 · Cited by 129 · see citing works
Exercise and intestinal permeability: another form of exercise-induced hormesis?
Keirns, B. H., Koemel, N. A., Sciarrillo, C. M., Anderson, K. L., & Emerson, S. R. (2020) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00232.2020 · Cited by 121 · see citing works
Snipe, R. M. J., Khoo, A., Kitic, C. M., Gibson, P. R., & Costa, R. J. S. (2017) · Applied Physiology Nutrition and Metabolism · doi:10.1139/apnm-2017-0361 · Cited by 117 · see citing works
“…solution maintains portal vein blood flow during exercise (Rehrer et al. 2005); 2) I-FABP levels correlate well with splanchnic perfusion (van Wijck et al. 2011); and 3) no differences in I-FABP were found between GLUC and WPH, it is likely repeated macronutrient feeding ameliorates…”
BackgroundFour weeks of probiotic supplementation reduces GI symptoms during a marathon race
Pugh, J. N., Sparks, A. S., Doran, D. A., Fleming, S. C., Langan-Evans, C., Kirk, B., Fearn, R., Morton, J. P., & Close, G. L. (2019) · European Journal of Applied Physiology · doi:10.1007/s00421-019-04136-3 · Cited by 115 · see citing works
Is There an Exercise-Intensity Threshold Capable of Avoiding the Leaky Gut?
Ribeiro, F. M., Petriz, B. A., Marques, G., Kamilla, L. H., & Franco, O. L. (2021) · Frontiers in Nutrition · doi:10.3389/fnut.2021.627289 · Cited by 118 · see citing works
“The intestinal mucosa’s degradation can be identified and analyzed by a series of molecular biomarkers, including the lactulose/rhamnose ratio, occludin and claudin (tight junctions), lipopolysaccharides, and I-FABP.”
BackgroundInfluentialGonzalez, J. T., Veasey, R. C., Rumbold, P. L. S., & Stevenson, E. J. (2013) · British Journal of Nutrition · doi:10.1017/s0007114512005582 · Cited by 108 · see citing works
“However, recent evidence associates the increase in intestinal absorption 364 with reduced gut blood flow occurring during intense exercise and may result in intestinal 365 damage((40)), indicating faster entry of glucose into the circulation when gut blood flow is reduced 366 [which occurs when exercising fasted comp…”
BackgroundAggravation of Exercise-Induced Intestinal Injury by Ibuprofen in Athletes
van Wijck, K., Lenaerts, K., van Bijnen, A. A. J. H. M., Boonen, B., van Loon, L. J. C., Dejong, C. H. C., & Buurman, W. A. (2012) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e318265dd3d · Cited by 107 · see citing works
“Furthermore, all 15 athletes participating in our previous study had normal hydration status and no detectable kidney damage after completion of the same exercise protocol as applied in the current study (33).”
InfluentialSelf-citationCosta, R. J. S., Gaskell, S. K., McCubbin, A. J., & Snipe, R. M. J. (2019) · Temperature · doi:10.1080/23328940.2019.1597676 · Cited by 101 · see citing works
High-altitude exposures and intestinal barrier dysfunction
McKenna, Z. J., Pereira, F. G., Gillum, T., Amorim, F. T., Deyhle, M. R., & Mermier, C. M. (2022) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00270.2021 · Cited by 103 · see citing works
van Wijck, K., Pennings, B., van Bijnen, A. A. J. H. M., Senden, J. M., Buurman, W. A., Dejong, C. H. C., van Loon, L. J. C., & Lenaerts, K. (2013) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00294.2012 · Cited by 100 · see citing works
“Previously, we demonstrated that exercise-induced small intestinal injury is caused by splanchnic hypoperfusion (30).”
BackgroundResultInfluentialSelf-citationRoberts, J., Suckling, C., Peedle, G., Murphy, J., Dawkins, T., & Roberts, M. (2016) · Nutrients · doi:10.3390/nu8110733 · Cited by 99 · see citing works
“It has been shown that exercise induced GI hypoperfusion may provoke transient damage to the gut epithelium [6], with one study demonstrating that 30 min of running at 80% of peak oxygen uptake (VO2peak) significantly increased luminal permeability in healthy volunteers [7].”
BackgroundIntestinal fatty acid-binding protein and gut permeability responses to exercise
March, D. S., Marchbank, T., Playford, R. J., Jones, A. W., Thatcher, R., & Davison, G. (2017) · European Journal of Applied Physiology · doi:10.1007/s00421-017-3582-4 · Cited by 110 · see citing works
Alterations in Intestinal Permeability: The Role of the “Leaky Gut” in Health and Disease
Stewart, A. S., Pratt-Phillips, S. E., & Gonzalez, L. M. (2017) · Journal of Equine Veterinary Science · doi:10.1016/j.jevs.2017.02.009 · Cited by 100 · see citing works
“Shunting of the blood from visceral tissues to more active tissues during exercise can therefore result in varying degrees of intestinal damage including alterations in permeability [49,50].”
BackgroundRoles of the gut microbiome in weight management
Carmody, R. N., & Bisanz, J. E. (2023) · Nature Reviews Microbiology · doi:10.1038/s41579-023-00888-0 · Cited by 105 · see citing works
Karhu, E., Forsgård, R. A., Alanko, L., Alfthan, H. V., Pussinen, P. J., Hämäläinen, E. K., & Korpela, R. (2017) · European Journal of Applied Physiology · doi:10.1007/s00421-017-3739-1 · Cited by 96 · see citing works
Zuo, L., Li, Y., Wang, H., Wu, R., Zhu, W., Zhang, W., Cao, L., Gu, L., Gong, J., Li, N., et al. (2014) · Journal of Crohn s and Colitis · doi:10.1016/j.crohns.2014.08.008 · Cited by 94 · see citing works
Effects of Protein Supplementation on Performance and Recovery in Resistance and Endurance Training
Cintineo, H. P., Arent, M. A., António, J., & Arent, S. M. (2018) · Frontiers in Nutrition · doi:10.3389/fnut.2018.00083 · Cited by 92 · see citing works
Effects of physical activity upon the liver
Shephard, R. J., & Johnson, N. A. (2014) · European Journal of Applied Physiology · doi:10.1007/s00421-014-3031-6 · Cited by 88 · see citing works
Exploring the influence of the gut microbiota and probiotics on health: a symposium report
Thomas, L. V., Ockhuizen, T., & Suzuki, K. (2014) · British Journal Of Nutrition · doi:10.1017/s0007114514001275 · Cited by 89 · see citing works
Mitochondrial ATP Depletion Disrupts Caco-2 Monolayer Integrity and Internalizes Claudin 7
JanssenDuijghuijsen, L. M., Grefte, S., de Boer, V. C. J., Zeper, L. W., van Dartel, D. A. M., van der Stelt, I., Bekkenkamp‐Grovenstein, M., van Norren, K., Wichers, H. J., & Keijer, J. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.00794 · Cited by 86 · see citing works
“Several in vivo studies indirectly support this hypothesis, such as exercise studies that show an exerciseinduced splanchnic hypoperfusion (Van Wijck et al., 2011) and exercise-induced intestinal permeability (Van Wijck et al., 2011; JanssenDuijghuijsen et al., 2016, 2017).”
BackgroundSnipe, R. M. J., Khoo, A., Kitic, C. M., Gibson, P., & Costa, R. J. S. (2018) · International Journal of Sports Medicine · doi:10.1055/s-0043-122742 · Cited by 84 · see citing works
“Statistical analysis Based on a standard deviation of 118 pg · ml − 1 for post-exercise IFABP [40] and using a standard alpha (0.”
BackgroundMethodInfluentialL-Citrulline Improves Splanchnic Perfusion and Reduces Gut Injury during Exercise
van Wijck, K., Wijnands, K. A. P., Meesters, D. M., Boonen, B., van Loon, L. J. C., Buurman, W. A., Dejong, C. H. C., Lenaerts, K., & Poeze, M. (2014) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000000332 · Cited by 83 · see citing works
“We have recently demonstrated that splanchnic hypoperfusion is associated with small intestinal injury and loss of gut barrier function in healthy men (33).”
BackgroundInfluentialSelf-citationRomán, E., Nieto, J. C., Gely, C., Vidal, S., Pozuelo, M., Poca, M., Juárez, C., Guarner, C., Manichanh, C., & Soriano, G. (2019) · Hepatology Communications · doi:10.1002/hep4.1325 · Cited by 80 · see citing works
“Nevertheless, we would like to point out that the results from the biomarkers used in the present study that could suggest an improvement in the intestinal barrier after probiotic treatment are consistent with previous data.(23,38-45) As future research, a study with a larger number of patients and with a longer treat…”
ResultChantler, S., Griffiths, A., Matu, J., Davison, G., Jones, B. L., & Deighton, K. (2020) · Sports Medicine · doi:10.1007/s40279-020-01348-y · Cited by 80 · see citing works
Regulation of Cellular Gas Exchange, Oxygen Sensing, and Metabolic Control
Clanton, T. L., Hogan, M. C., & Gladden, L. B. (2013) · Comprehensive physiology · doi:10.1002/cphy.c120030 · Cited by 88 · see citing works
Davison, G., Marchbank, T., March, D. S., Thatcher, R., & Playford, R. J. (2016) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.116.134403 · Cited by 79 · see citing works
Liu, T.-W., Park, Y.-M., Holscher, H. D., Padilla, J., Scroggins, R. J., Welly, R., Britton, S. L., Koch, L. G., Vieira-Potter, V. J., & Swanson, K. S. (2015) · PLOS ONE · doi:10.1371/journal.pone.0136150 · Cited by 78 · see citing works
“High-intensity exercise redirects blood flow to the active tissues such as skeletal muscle and heart [33].”
BackgroundIncreased Small Intestinal Permeability during Severe Acute Exacerbations of COPD
Sprooten, R. T. M., Lenaerts, K., Braeken, D. C. W., Grimbergen, I., Rutten, E. P. A., Wouters, E. F. �., & Rohde, G. G. U. (2018) · Respiration · doi:10.1159/000485935 · Cited by 76 · see citing works
Self-citationOgden, H. B., Child, R. B., Fallowfield, J. L., Delves, S. K., Westwood, C. S., & Layden, J. D. (2020) · Nutrients · doi:10.3390/nu12020537 · Cited by 76 · see citing works
“In the only published evidence where the MSAT was applied with reference probe co-administration [82], both gastroduodenal (S/R; [123]) and large intestinal (S/E; [86]) integrity were unaltered following one hour of moderate intensity cycling (70% wattmax) in temperate conditions (~22 °C), which was sufficiently inten…”
BackgroundMethodResultInfluentialSports Dietitians Australia Position Statement: Nutrition for Exercise in Hot Environments
McCubbin, A. J., Allanson, B. A., Caldwell Odgers, J. N., Cort, M. M., Costa, R. J. S., Cox, G. R., Crawshay, S. T., Desbrow, B., Freney, E. G., Gaskell, S. K., et al. (2020) · International Journal of Sport Nutrition and Exercise Metabolism · doi:10.1123/ijsnem.2019-0300 · Cited by 74 · see citing works
“…of blood flow away from the gastrointestinal tract and toward skeletal muscles (i.e., metabolic kinetics) and peripheral circulation (i.e., thermoregulation) results in reduced total splanchnic perfusion and subsequent gastrointestinal ischemia (Grootjans et al., 2016; van Wijck et al., 2011).”
BackgroundNo Effects of a Short-Term Gluten-free Diet on Performance in Nonceliac Athletes
Lis, D. M., Stellingwerff, T., Kitic, C. M., Ahuja, K., & Fell, J. W. (2015) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000000699 · Cited by 72 · see citing works
“Preexercise IFABP levels were within expected ranges of healthy controls and increased in accordance with similar exercise studies across both dietary trials during the performance test (40).”
BackgroundMethodResultInfluentialBeta-Hydroxybutyrate: A Dual Function Molecular and Immunological Barrier Function Regulator
Qi, J., Gan, L., Fang, J. S., Zhang, J., Yu, X., Guo, H., Cai, D., Cui, H., Gou, L., Deng, J., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.805881 · Cited by 72 · see citing works
Townsend, J. R., Bender, D., Vantrease, W. C., Sapp, P. A., Toy, A. M., Woods, C. A., & Johnson, K. D. (2018) · Sports · doi:10.3390/sports6030070 · Cited by 69 · see citing works
Boytar, A. N., Skinner, T. L., Wallen, R. E., Jenkins, D. G., & Nitert, M. D. (2023) · Nutrients · doi:10.3390/nu15061534 · Cited by 75 · see citing works
Scientific uncertainty in media content: Introduction to this special issue
Peters, H. P., & Dunwoody, S. (2016) · Public Understanding of Science · doi:10.1177/0963662516670765 · Cited by 71 · see citing works
Pugh, J. N., Impey, S. G., Doran, D. A., Fleming, S. C., Morton, J. P., & Close, G. L. (2017) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2016-0646 · Cited by 70 · see citing works
“Situated between these ends of the symptomology continuum, acute exercise activity may also impact upon digestion, absorption and importantly, the recovery process (Riddoch et al. 1988; van Wijck et al. 2013a; de Oliveira et al. 2014).”
Hawley, J. A., Forster, S. C., & Giles, E. M. (2025) · Gastroenterology · doi:10.1053/j.gastro.2025.01.224 · Cited by 69 · see citing works
Cancer Related Anemia: An Integrated Multitarget Approach and Lifestyle Interventions
Natalucci, V., Virgili, E., Calcagnoli, F., Valli, G., Agostini, D., Zeppa, S. D., Barbieri, E., & Emili, R. (2021) · Nutrients · doi:10.3390/nu13020482 · Cited by 70 · see citing works
Nieman, D. C., Scherr, J., Luo, B., Meaney, M. P., Dréau, D., Sha, W., Dew, D. A., Henson, D. A., & Pappan, K. L. (2014) · PLoS ONE · doi:10.1371/journal.pone.0113725 · Cited by 66 · see citing works
“Plasma sucrose is widely used as a marker of increased gastrointestinal permeability [22].”
BackgroundPu, H., Doig, G. S., Heighes, P. T., & Allingstrup, M. J. (2018) · Critical Care Medicine · doi:10.1097/ccm.0000000000003445 · Cited by 69 · see citing works
Pugh, J. N., Sage, S., Hutson, M., Doran, D. A., Fleming, S. C., Highton, J., Morton, J. P., & Close, G. L. (2017) · European Journal of Applied Physiology · doi:10.1007/s00421-017-3744-4 · Cited by 64 · see citing works
Oxygen in the regulation of intestinal epithelial transport
Ward, J. B. J., Keely, S., & Keely, S. J. (2014) · The Journal of Physiology · doi:10.1113/jphysiol.2013.270249 · Cited by 64 · see citing works
“Although the intestines are able to utilise oxygen more efficiently during hypoperfusion, strenuous exercise has been associated with gut dysfunction in healthy individuals (van Wijck et al. 2011, 2012; ter Steege & Kolkman, 2012).”
BackgroundInteractions of Gut Microbiota, Endotoxemia, Immune Function, and Diet in Exertional Heatstroke
Armstrong, L. E., Lee, E. C., & Armstrong, E. M. (2018) · Journal of Sports Medicine · doi:10.1155/2018/5724575 · Cited by 63 · see citing works
“Intestinal ischemia has been shown to occur within 10–20min of high-intensity exercise [91].”
BackgroundToohey, J. C., Townsend, J. R., Johnson, S. B., Toy, A. M., Vantrease, W. C., Bender, D., Crimi, C. C., Stowers, K. L., Ruiz, M. D., VanDusseldorp, T. A., et al. (2020) · Journal of Strength and Conditioning Research · doi:10.1519/jsc.0000000000002675 · Cited by 62 · see citing works
“It has been previously reported that high-intensity interval training and resistance exercises increase markers of intestinal damage (30,37) and may impair dietary protein digestion and absorption during postexercise recovery (38).”
BackgroundBiomarkers of multiorgan injury in a preclinical model of exertional heat stroke
King, M. A., Leon, L. R., Mustico, D. L., Haines, J. M., & Clanton, T. L. (2015) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01051.2014 · Cited by 61 · see citing works
“Exertional heat stroke may be particularly susceptible to intestinal injury since in humans (68) and in mice (27); heavy endurance exercise alone can result in evidence for loss of the intestinal barrier function and enterocyte injury.”
BackgroundRisk factors for equine glandular and squamous gastric disease in show jumping Warmbloods
Pedersen, S. K., Cribb, A. E., Windeyer, M. C., Read, E. K., French, D., & Banse, H. E. (2018) · Equine Veterinary Journal · doi:10.1111/evj.12949 · Cited by 59 · see citing works
Snipe, R. M. J., & Costa, R. J. S. (2018) · Journal of science and medicine in sport · doi:10.1016/j.jsams.2017.12.014 · Cited by 58 · see citing works
Edinburgh, R. M., Hengist, A., Smith, H., Travers, R. L., Koumanov, F., Betts, J. A., Thompson, D., Walhin, J., Wallis, G. A., Hamilton, D. L., et al. (2018) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00163.2018 · Cited by 56 · see citing works
“Plasma IFABP concentrations are used as a marker of damage to intestinal epithelial cells (60).”
MethodBetaine Supplementation May Improve Heat Tolerance: Potential Mechanisms in Humans
Willingham, B. D., Ragland, T. J., & Ormsbee, M. J. (2020) · Nutrients · doi:10.3390/nu12102939 · Cited by 59 · see citing works
Costa, R. J. S., Young, P., Gill, S. K., Snipe, R. M. J., Gaskell, S. K., Russo, I., & Burke, L. M. (2022) · International Journal of Sport Nutrition and Exercise Metabolism · doi:10.1123/ijsnem.2022-0048 · Cited by 56 · see citing works
Lubbers, T., Kox, M., de Haan, J. J., Greve, J. W. M., Pompe, J. C., Ramakers, B. P., Pickkers, P., & Buurman, W. A. (2013) · Critical Care Medicine · doi:10.1097/ccm.0b013e31827c0a17 · Cited by 55 · see citing works
“Intestinal-fatty acid–binding protein (i-FABP), a marker of intestinal epithelial cell damage, was determined in plasma using an in-house developed, validated, and standardized enzymelinked immunosorbent assay (17, 18).”
MethodSelf-citationFructose and Sucrose Intake Increase Exogenous Carbohydrate Oxidation during Exercise
Trommelen, J., Fuchs, C., Beelen, M., Lenaerts, K., Jeukendrup, A., Cermak, N., & Van Loon, L. (2017) · Nutrients · doi:10.3390/nu9020167 · Cited by 55 · see citing works
“Previous work has shown that exercise resulted in a rapid appearance of this marker in blood, which correlated with splanchnic hypoperfusion [23].”
BackgroundSelf-citationNutritional implications for ultra-endurance walking and running events
Williamson, E. (2016) · Extreme Physiology & Medicine · doi:10.1186/s13728-016-0054-0 · Cited by 53 · see citing works
“However, it is likely that their needs would be even higher given the increase in total oxidation of amino acids during exercise as well as the possibility of splanchnic organ tissue damage due to the shunting of blood away from the digestive system during activity [91].”
BackgroundKittaka, H., Akimoto, H., Takeshita, H., Funaoka, H., Hazui, H., Okamoto, M., Kobata, H., & Ohishi, Y. (2014) · PLoS ONE · doi:10.1371/journal.pone.0099915 · Cited by 53 · see citing works
“Another study found a correlation between splanchnic hypoperfusion induced by cycling exercise and the plasma I-FABP level, reporting that the IFABP level increased rapidly 40 minutes after the initiation of cycling [44].”
BackgroundPugh, J. N., Wagenmakers, A. J. M., Doran, D. A., Fleming, S. C., Fielding, B. A., Morton, J. P., & Close, G. L. (2020) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00452.2019 · Cited by 48 · see citing works
Moitinho‐Silva, L., Wegener, M., May, S., Schrinner, F., Akhtar, A., Boysen, T. J., Schaeffer, E., Hansen, C., Schmidt, T., Rühlemann, M. C., et al. (2021) · BMC Microbiology · doi:10.1186/s12866-021-02214-1 · Cited by 46 · see citing works
March, D. S., Jones, A. W., Thatcher, R., & Davison, G. (2018) · European Journal of Nutrition · doi:10.1007/s00394-018-1670-9 · Cited by 57 · see citing works
Snipe, R. M. J., & Costa, R. J. S. (2018) · Journal of Sports Sciences · doi:10.1080/02640414.2018.1478612 · Cited by 46 · see citing works
“Such increases in I-FABP after 1 h exercise have been correlatedwith the magnitude of splanchnic hypoperfusion and increases in intestinal permeability (van Wijck et al., 2011).”
BackgroundLis, D. M. (2019) · Sports Medicine · doi:10.1007/s40279-018-01034-0 · Cited by 45 · see citing works
“GIS triggered by the physiological responses to exercise are instigated through two main pathways: (1) a circulatory-gastrointestinal pathway where blood flow is redistributed away from the splanchnic area to peripheral circulation and contracting muscles (termed splanchnic hypoperfusion); and (2) a neuroendocrine-gas…”
BackgroundHolland, A. M., Hyatt, H. W., Smuder, A. J., Sollanek, K. J., Morton, A. B., Roberts, M. D., & Kavazis, A. N. (2015) · BMC Research Notes · doi:10.1186/s13104-015-1500-6 · Cited by 43 · see citing works
Is There a Need for Protein Ingestion During Exercise?
van Loon, L. J. C. (2014) · Sports Medicine · doi:10.1007/s40279-014-0156-z · Cited by 45 · see citing works
The Impact of Morning versus Afternoon Exercise on Iron Absorption in Athletes
McCormick, R., Moretti, D., McKay, A. K. A., Laarakkers, C. M., vanSwelm, R., Trinder, D., Cox, G. R., Zimmermann, M. B., Sim, M., Goodman, C., et al. (2019) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000002026 · Cited by 47 · see citing works
“Alternatively, exercise has been shown to create a transient increase in the permeability of the small intestine (“leaky gut”) as a result of splanchnic hypoperfusion and repetitive mechanical movement during exercise, such outcomes are thought to increase the transfer of iron across the intestinal border (29,30).”
BackgroundGastric tonometry guided therapy in critical care patients: a systematic review and meta-analysis
Zhang, X., Xuan, W., Yin, P., Wang, L., Wu, X., & Wu, Q. (2015) · Critical Care · doi:10.1186/s13054-015-0739-6 · Cited by 42 · see citing works
The effect of endurance exercise on intestinal integrity in well‐trained healthy men
JanssenDuijghuijsen, L. M., Mensink, M., Lenaerts, K., Fiedorowicz, E., the Protégé study group, van Dartel, D. A. M., Mes, J. J., Luiking, Y. C., Keijer, J., Wichers, H. J., et al. (2016) · Physiological Reports · doi:10.14814/phy2.12994 · Cited by 42 · see citing works
“For example, FABP2, an acute enterocyte damage marker, was not affected in this study, while van Wijck et al. (2011a) found a clear increase in plasma FABP2 levels during and directly after exercise.”
BackgroundMethodInfluentialSelf-citationDexmedetomidine protects intestinal ischemia-reperfusion injury via inhibiting p38 MAPK cascades
Liu, X.-M., Chen, Q., Hu, Q., Liu, Z., Wu, Q., Liang, S., Zhang, H., Zhang, Q., & Zhang, X. (2020) · Experimental and Molecular Pathology · doi:10.1016/j.yexmp.2020.104444 · Cited by 42 · see citing works
Hasegawa, T., Mizugaki, A., Inoue, Y., Kato, H., & Murakami, H. (2021) · Amino Acids · doi:10.1007/s00726-021-03001-y · Cited by 42 · see citing works
Carbohydrate gel ingestion during running in the heat on markers of gastrointestinal distress
Sessions, J., Bourbeau, K., Rosinski, M. M., Szczygiel, T., Nelson, R. K., Sharma, N., & Zuhl, M. (2016) · European Journal of Sport Science · doi:10.1080/17461391.2016.1140231 · Cited by 41 · see citing works
“In addition, blood flow is diverted from the GI tract creating an ischemic environment enhancing oxidative stress (Lambert et al., 2002; van Wijck et al., 2011), which contributes to the loss of tight junction integrity.”
BackgroundHill, G. W., Gillum, T., Lee, B., Romano, P. A., Schall, Z. J., Hamilton, A. M., & Kuennen, M. R. (2019) · Applied Physiology Nutrition and Metabolism · doi:10.1139/apnm-2019-0378 · Cited by 40 · see citing works
“I-FABP is a robust biomarker of GI barrier permeability (Morrison et al. 2014) that exhibits strong correlations with splanchnic hypoperfusion (van Wijck et al. 2011), the lactulose/rhamanose gut permeability test (Pugh et al. 2017), and plasma LPS concentrations (Kim et al. 2018).”
BackgroundSmith, K. A., Pugh, J. N., Duca, F. A., Close, G. L., & Ormsbee, M. J. (2021) · European Journal of Applied Physiology · doi:10.1007/s00421-021-04737-x · Cited by 41 · see citing works
- Authors
- van Wijck, K., Lenaerts, K., van Loon, L. J. C., Peters, W. H. M., Buurman, W. A., & Dejong, C. H. C.
- Affiliations
- Maastricht University Medical Centre (NL)
- Radboud University Nijmegen (NL)
- Corresponding author
- Lenaerts, Kaatje
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-07-21
- Volume
- 6
- Issue
- 7
- Pages
- e22366
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3141050
- OpenAlex
- W1986330043
- Cited by
- 359
- References
- 48
- Citations by year
- 2026: 26 · 2025: 28 · 2024: 21 · 2023: 32 · 2022: 32 · 2021: 33 · 2020: 30 · 2019: 24 · 2018: 24 · 2017: 27 · 2016: 18 · 2015: 12 · 2014: 17 · 2013: 18 · 2012: 15
- FWCI
- 16.54
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Research Bank (Australian Catholic University) (submittedVersion, cc-by)
- Research Publications (Maastricht University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Radboud Repository (Radboud University) (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Funders
- GlaxoSmithKline
- Topics
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Keywords
- splanchnic hypoperfusion, physical activity, gastrointestinal dysfunction, intestinal injury, intestinal permeability, intestinal barrier dysfunction, gastric tonometry, intestinal fatty acid binding protein, ileal bile acid binding protein, small intestine, healthy men
- MeSH terms
- Bacteria, Health, Humans, Inflammation, Kidney, Liver, Male, Perfusion, Permeability, Splanchnic Circulation, Exercise, Gastrointestinal Tract, Young Adult
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