The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
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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In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“It has been shown that exercise induced GI hypoperfusion may provoke transient damage to the gut epithelium [6]”
In the citing paper
“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]
In the citing paper
“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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Citations
Cites
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“Since evidence is accumulating that inflammatory products are produced in contracting and skeletal muscle [32,45], we determined both circulating and faecal calprotectin.”
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“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×
“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×
“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 586 · cited 1×
“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
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×
“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×
“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×
“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×
“Alternatively, muscle transaminase release is expected in response to (exerciseinduced) muscle injury [23,24], while L-FABP release could be due to intestinal damage.”
Background
Cited by
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
“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
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
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
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
“Exercise also can reduce intestinal blood flow by more than 50%, with significant gut ischemia occurring within 10 min of high-intensity exercise (69).”
Background
Metadata
- 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 › Physiology (medical) › Exercise and Physiological Responses
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Physiology (medical) › 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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