Your trusted health, nutrition, and personalized lifestyle medicine resource

Exercise: Impact on the Gut-Brain Axis

Practical tips to support the delicate GI balance

by Sara Gottfried, MD and Noelle Patno, PhD 

Exercise. We all know we need it to reduce the risk of cardiovascular disease, improve mood, maintain a healthy weight, and support neurogenesis, among many other health benefits. We all know to counsel our patients about it. However, what many practitioners don’t realize is that exercise triggers a stress response in the body, impacting the gastrointestinal system as well as the overall body’s physiology, and may result in disruption of the delicate gut-brain axis.

In scientific terms, the stress response triggered by exercise is called hormesis. According to Merriam-Webster, hormesis is “a theoretical phenomenon of dose-response relationships in which something (as a heavy metal or ionizing radiation) that produces harmful biological effects at moderate to high doses may produce beneficial effects at low doses.” Higher levels of exercise can be considered hermetic, particularly when one considers integrity of the tight junctions in the gut epithelium.

When it comes to the connection between the gut and brain, most people understand that the brain can affect the gut, but don’t consider how gut function impacts the function of the brain. This bidirectional relationship is often described as the gut-brain axis, or GBA. The gut-brain axis definition refers to the vast communication between the gut (and its enteric nervous system) and the brain (also called the central nervous system). The gut-brain axis also involves microbes and their activities in the intestine. Inflammation, intestinal hyperpermeability (or “leaky gut”), antibiotic use, excessive intake of sugar and inflammatory fats, not enough prebiotic foods, overreactive responses or lack of tolerance to food, and major stresses can negatively impact the gut-brain axis. These kinds of stresses also may cause dysbiosis or altered microbial communities in the gut, which is another way to disrupt the gut-brain axis (GBA).

Exercise and the GBA

Exercise affects the gut-brain axis. An increase in moderate exercise causes greater diversity, which is associated with a healthier environment in the intestine.1 While moderate exercise has a beneficial influence on many health outcomes, such as increasing blood flow and oxygenation or reducing constipation and the risk of colon cancer, excessive exercise can result in increases in intestinal permeability that may be detrimental to heath.2 Bacterial translocation across the hyperpermeable gut may lead to undesired health consequences. Elite athletes and those who train intensely without adequate recovery may be at risk of gastrointestinal distress and disturbances to the GBA.2 Endurance athletes in particular may experience disruptions to the gut-brain axis as their bodies need to adjust to the increased oxidation stress, intestinal hyperpermeability, muscle damage, systemic inflammatory response, decreased glycogen storage, and electrolyte balance shift during long periods of cardiovascular exercise.1

Disruption of the gut-brain axis typically starts with gastrointestinal symptoms. An estimated 30-50% of athletes may suffer from bloating, flatulence, stomach pain/cramps, diarrhea, and nausea.2 In addition to these gastrointestinal symptoms, people may experience fatigue, insomnia, irritability, anxiety, poor concentration, depression, and other symptoms of stress simultaneously. Based on clinical experience, patients present with classic symptoms of gastrointestinal disturbances as well as loose stools, sensitivity to gluten and dairy, acid reflux, and difficulty losing weight. Gut disturbances may also manifest as larger inflammatory indicators, possibly through the endotoxin leakage across the gut, resulting in brain fog, anxiety, moodiness, feeling swollen or puffy, and early memory loss.

Probiotics, exercise, and GBA

Probiotic supplementation is widely used to support general immune and gastrointestinal function,3 and there is increasing evidence to suggest that probiotics impact the brain as well.4 In meta-analyses, probiotics have been demonstrated to reduce the number of people experiencing colds and reduce the duration of colds.5,6 Modulating the microbiota through diet may help improve microbial metabolites during exercise and mitigate the harmful consequences of stress.7 Based on a review of the literature on endurance exercise and gut microbiota, evidence supports the hypothesis that probiotic supplementation may be a useful therapy for improving athletes’ overall general health, performance, and metabolism and energy expenditure as well as managing inflammation and oxidative stress.1

Since a recent meta-analysis identified that the efficacy of probiotics is strain-dependent and condition-specific,8 more research is needed to identify the strains that are effective for athletes to maintain healthy gut and brain function. Emerging research suggests that specific strains of bacteria may help mitigate inflammation and leaky gut in exercise. A pair of strains decreased inflammatory markers after exercise.9 In a randomized, double-blind crossover study, it was noted that consuming an existing, clinically used strain called L. salivarius UCC118 prevented sugar from leaking across the gut in highly trained endurance athletes.10 Future psychobiotics applicable to the active person will be on the horizon.

How to improve gut-brain axis function

Existing research supports other types of supplementation to support the GBA. Taking vitamin C can reduce the rise in cortisol during intense exercise.11-14 Remember that the releasing hormone for cortisol, corticotropin-releasing hormone (CRH), can be the root cause of increased intestinal permeability,15-19 so vitamin C may act as a buffer.

L-carnitine assists in cellular production of energy and breakdown of fatty acids,20 which is important in muscle activity. Studies of L-carnitine supplementation in athletes show some improvements in recovery and prevention of cellular damage.21 Some research suggests that L-carnitine protects and supports gut microbiota and seems to affect bacterial metabolism while at the same time influencing fiber metabolism.22 There seems to be an interaction between L-carnitine metabolism by gut microbiota, which may be associated with an increased risk of cardiovascular disease even though L-carnitine consumption seems to protect against metabolic diseases by increasing the metabolism of glucose in heart and muscle.23 These differing effects point to the importance of a proper balance of fiber and L-carnitine intake and metabolism for overall health.

Branched-chain amino acids (BCAAs) may benefit an active lifestyle. Some research indicates that branched-chain amino acid supplementation promotes nutrition, intestinal development, and health.24 They may also help with energy levels, regulate metabolism, and support the gut.25


High levels of exercise may cause a hormetic effect on the body, particularly the gut-brain axis, during training. Without proper care and maintenance of the gut-brain axis, athletes may experience worsening or consistent inflammation, poor performance and recovery, anxiety, and depression and may even develop autoimmune conditions. Besides proper hydration, nutrition, rest, recovery, and physical therapy, supplementation may mitigate the damage induced by intense exercise. Taking a proactive approach to self-care through personalized lifestyle medicine may help athletes strengthen their gut-brain axis function in order to support their future athletic performance.


  1. Mach N et al. J Sport Health Sci. 2017;6(2):179-197.
  2. Pane M et al. J Clin Gastroenterol. 2018;52 Suppl 1:S46-S49.
  3. Garisch J et al. J Clin Gastroenterol. 2012;46(6):14.
  4. Sampson TR et al. Cell Host & Microbe. 2015;17(5):565-576.
  5. Hao Q et al. Probiotics for preventing acute upper respiratory tract infections. In: The Cochrane Library. John Wiley & Sons, Ltd; 2015.
  6. Kang E-J et al. Korean J Fam Med. 2013;34(1):2-10.
  7. Clark A et al. J Int Soc Sports Nutr. 2016;13.
  8. McFarland LV et al. Frontiers in Medicine. 2018;5.
  9. Jäger R et al. Nutrients. 2016;8(10):642.
  10. Brennan CJ et al. Poster presented at: American College of Sports Medicine Annual Meeting 2018; May 29, 2018; Minneapolis, MN.
  11. Peters EM et al. Int J Sports Med. 2001;22(07):537-543.
  12. Carrillo AE et al. Int J Sports Physiol Perform. 2008;3(4):516-530.
  13. Nieman DC et al. Journal of Interferon & Cytokine Research. 2000;20(11):1029-1035.
  14. Davison G et al. Medicine & Science in Sports & Exercise. 2007;39(4):645-652.
  15. Yu Y et al. PLoS One. 2013;8(6).
  16. Vanuytsel T et al. Gut. 2014;63(8):1293-1299.
  17. Larauche M et al. J Physiol Pharmacol. 2009;60(Suppl 7):33-46.
  18. Keita ÅV et al. Neurogastroenterology & Motility. 2010;22(7):718-733.
  19. Overman EL et al. PLoS One. 2012;7(6).
  20. Flanagan JL et al. Nutr Metab (Lond). 2010;7:30.
  21. Fielding R et al. Nutrients. 2018;10(3).
  22. Ghonimy A et al. Int J Mol Sci. 2018;19(4).
  23. Ussher JR et al. Atherosclerosis. 2013;231(2):456-461.
  24. Zhou H et al. Animal Science Journal. 2018;89(1):3-11.
  25. Bifari F et al. Genes Nutr. 2017;12.


Sara Gottfried, MD is a board-certified gynecologist and physician scientist. She graduated from Harvard Medical School and the Massachusetts Institute of Technology and completed residency at the University of California at San Francisco. Over the past two decades, Dr. Gottfried has seen more than 25,000 patients and specializes in identifying the underlying cause of her patients’ conditions to achieve true and lasting health transformations, not just symptom management.

Dr. Gottfried is a global keynote speaker who practices evidence-based integrative, precision, and Functional Medicine. She recently published a new book, Brain Body Diet and has also authored three New York Times bestselling books: The Hormone Cure, The Hormone Reset Diet, and Younger.

Noelle Patno, PhD received her PhD in Molecular Metabolism and Nutrition and Masters in Translational Science from the University of Chicago, studying the role of microbial components in intestinal epithelial cell survival related to inflammatory bowel disease. Prior to her graduate studies, Dr. Patno received a chemical engineering degree from Stanford University and worked as an engineer. She has personal experience and interest in preventive nutrition and nutritional therapies for chronic disease, and her current role involves researching and developing probiotics, prebiotics, and other nutritional programs for the promotion of digestive and overall health.

Leave a Reply

Metagenics Institute is a trusted, peer-to-peer, evidence-based educational resource for nutrition and personalized medicine.
At Metagenics Institute, we translate credible research with scientific integrity into innovative and actionable clinical
decision-making. Metagenics Institute supports a diverse practitioner base to optimize patient outcomes by shifting existing paradigms in healthcare. Our mission is to transform healthcare by inspiring and educating practitioners, and their patients, about personalized lifestyle medicine.

Sponsored by
© 2024 Metagenics Institute. All Rights Reserved