Exercise effects on gut microbiome and brain health

It's well-established that exercise can boost cardiovascular function, mental health, and metabolism. For example, high-intensity interval training (HIIT) was shown to improve insulin sensitivity and increase muscle mitochondrial capacity in obese patients. Exercise normally reduces the risk of GI cancer, reflux, and the incidence of ulcers, fatty liver, IBS, and diverticulitis.[1, 2, 3]

Strikingly, research is revealing that many of the significant impacts of exercise on neurotransmitter, epigenetic, hormonal, metabolic, energy-related, and inflammatory signaling are mediated by changes in the composition and function of the gut microbiome. In this article, we'll cover the effects of exercise on the gut microbiome, brain health and mood, hunger, and the immune system, and delineate the merits of athleticism over a sedentary lifestyle.

Exercise effects on gut microbiome and brain health

• Meet your second brain and endocrine organ

• 6 Benefits of exercise on gut-brain health

  • Increased brain serotonin and dopamine

  • Higher satiety and less hunger

  • Increased intestinal motility and integrity

  • Thinner villi and lower gut inflammation

  • Reduced gut Cox2 expression

  • Strengthened antioxidant capacity and lymphocyte homeostasis

• Microbiome of athletes vs. sedentary individuals

  • Biodiversity

  • Butyrate

  • Akkermansia muciniphila

  • Proteobacteria and Acidobacteria

• Intensity of exercise

• Types of exercise e.g. strength training

• Key takeaways

• References

Meet your second brain and endocrine organ

The enteric nervous system, the network of neurons innervating the GI tract, has been called the second brain because it's the largest component of the autonomic nervous system, numbering around 100 million neurons. The vagus nerve runs from the brain stem to the heart, lungs, gut, and other organs. This is one key way the microbiome communicates with the brain, apart from releasing metabolites into systemic circulation.

The gut microbiota has been proposed by scientists to be designated as an endocrine organ because of its widespread interactions with host physiology. Gut microbes can produce neurotransmitters like serotonin and dopamine.[4] They can also neutralize carcinogens and control oxidative stress and inflammatory responses.[5]

6 Benefits of Exercise on Gut-Brain Health

1. Exercise increases serotonin and dopamine, improving mood

You may notice increased energy and mental clarity after a great workout. This is no coincidence: exercise increases serotonin and dopamine levels in the brain.[5] Rats that swam briefly and regularly had increased levels of serotonin in the brainstem and hypothalamus.[6] Running at low speed also increased brain serotonin and decreased depressive and anxious behavior in rats.[7]

2. Exercise increases satiety and decreases hunger

Light to moderate exercise can make you feel less hungry, thanks to the interplay between gut microbes and hormones. Exercise increases the abundance of two mutualistic bacterial genera, Bifidobacterium and Lactobacillus, which are both associated with increased level of leptin, a satiety hormone. Meanwhile, exercise decreases secretion of ghrelin, a hunger hormone associated with increased Bacteroides and Prevotella.[8, 9] Exercise was found to decrease insulin, IL-6, and VLDL secretion.[9]

3. Exercise stimulates GI motility, which improves intestinal integrity

Exercise also indirectly preserves the gut barrier by stimulating GI motility. By reducing transient stool time, exercise minimizes contact between potential pathogens and the GI mucosa. This partly explains the decreased risk of colon cancer, diverticulosis, IBD, and hemorrhage in individuals who exercise.

4. Exercise kept villi thinner, a sign of lower gut inflammation

A team at Rutgers University investigated the effect of diet (normal vs. high-fat diet (HFD)) and exercise (active vs. sedentary) on inflammation, intestinal permeability, and microbiota. They found obese (HFD) sedentary mice had twice the gut villi width of lean sedentary animals. A major cause of villi widening was an increase in inflammatory cells in lymph and plasma cells and fat cells. The HFD exercised animals had normal villi.[2]

5. Exercise reduced Cox2 expression in the gut

The same Rutgers study looked at the expression of an enzyme called Cox2 that produces prostaglandins, which promotes inflammation, pain, and fever. Obese sedentary mice had the highest Cox2 expression, followed by lean sedentary and lean exercised mice. Surprisingly, obese exercised mice had the lowest Cox2 expression.[2]

This suggested that not only is a sedentary lifestyle a risk factor for inflammation even in lean individuals, but also that exercise can make a huge difference for obese individuals eating a high-fat diet.

6. Exercise upregulates antioxidant enzymes and has anti-inflammatory, pro-survival effect in intestinal lymphocytes

Exercise increased expression of glutathione peroxidase and catalase, anti-inflammatory cytokine IL-10, and pro-survival protein Bcl-2 in intestinal lymphocytes. This promoted the survival of intestinal lymphocytes and increased their numbers. By the same token, exercise decreased expression of pro-inflammatory cytokines TNF-alpha and IL-17, apoptotic proteins caspases 3 and 7, and reactive oxygen species (ROS) generation in intestinal lymphocytes.[10]

How do gut microbiota differ in athletes and sedentary individuals?

Exercise changes the diversity and composition of gut microbiota in specific ways. For example, athletes have higher levels of butyrate and increased Faecalibacterium prausnitzii and Akkermansia muciniphila, while sedentary individuals have higher Proteobacteria and Acidobacteria.

1. Exercise enriches biodiversity

Low microbial diversity is associated with more adiposity, insulin resistance, and inflammation; it's also a risk factor for weight gain. Exercise such as running can enhance the number of beneficial microbial species and improve host health.[9, 11] HIIT was also found to increase alpha diversity in mice; this effect was more pronounced in the distal gut, where it makes a difference in colon health.[12]

2. Exercise expands butyrate-producing bacteria

Certain bacteria convert plant-based carbohydrates (fiber) into short-chain fatty acids (SCFAs), an indicator of gut health. SCFAs like acetate, propionate, butyrate enhance barrier function, reduce inflammation, provide energy for colonocytes, prevent mucosal degradation, and overall protect the GI tract.[9]

SCFA-producing bacteria include Faecalibacterium prausnitzii, Lactobacillus, Bifidobacterium, Clostridium, Bacteroides, Roseburia, and Lachnospiraceae.[9] In particular, Lactobacillus and Bifidobacterium enhance absorption of vitamins and minerals.[13] Exercise, including cardio, has been found to increase numbers and diversity of these butyrate producers.[9, 14]

Higher Faecalibacterium prausnitzii was found in elite rugby players as well as in female athletes.[11] Additionally, female athletes had more Roseburia hominis and Prevotella.[15] When levels of these bacteria increase, so do levels of SCFAs and their associated benefits.

3. Exercise expands mucus-degrading Akkermansia muciniphila

Athletes (both men and women) have higher mucus-degrading Akkermansia muciniphila,[16] which improves mucus turnover and helps to maintain the gut barrier.[15] A substantial body of literature suggests A. muciniphila plays a role in mucosal homeostasis.

On the flipside, A. muciniphila is also elevated in patients with multiple sclerosis that present with leaky gut. One possible reason is excessively thin mucus and insufficient turnover. Conversely, thick mucus (caused by inflammatory diet or infection) can also increase levels of pathogenic mucus degraders. Overall, when it comes to gut mucosa, it’s all about balance and homeostatic turnover.

4. Sedentary lifestyle increases inflammatory Proteobacteria and Acidobacteria

Sedentary individuals may have higher levels of pathogenic, inflammatory Proteobacteria compared to active individuals.[17] Acidobacteria was also found to be higher in sedentary women.[15] Additionally, the beneficial butyrate-producing bacteria, Faecalibacterium prausnitzii, was high in active mice but not found in sedentary mice.[2] Overall, poor diet, sedentary lifestyle, antibiotics, and other factors can lower biodiversity, which increases risk of pathogenic bacteria dominating the gut.

When intense exercise becomes gut stress & when to not exercise

Running is known for its adrenaline rush. But prolonged stressful, fight-or-flight situations release norepinephrine and cortisol, which have inhibitory effects on the gut. Endurance cardio increases blood flow to the muscles, heart, and lungs and decreases blood flow to the small and large intestines. This decreased blood flow to the gut can increase tight junction opening, resulting in leaky gut. Leaky gut, potentially caused by dehydration, allows bacterial LPS translocation, which triggers the host's immune system to release inflammatory molecules like TNF-a, IFN-gamma, IL-1B, histamine, and proteases.[18, 19] The process can continue and lead to endotoxemia. In fact, marathon runners and triathletes frequently report symptoms like nausea, cramping, vomiting, or diarrhea.[5] However, it is possible that this effect could be mitigated with adequate training. Decreased blood flow to the gut was shown in foxhounds to wear off after 8-12 weeks of training.[20]

Exercising to exhaustion is not recommended because it temporarily weakens the immune system and increases inflammation.[5] This is why individuals fighting a cold are advised to wait about 48 hours for recovery before returning to the gym. Patients with chronic fatigue syndrome show worsening gut dysbiosis, inflammation, pain, and mood following exercise.[21] Overall, the more strenuous the exercise and the more depleted the energy reserves, the greater the barrier disruption, due to changes in blood flow and insufficient removal of metabolites and delivery of nutrients.[2]

How do resistance training, calisthenics, stretching, and yoga affect gut microbiota?

Type and intensity of exercise clearly matters, but to my knowledge, there are no published peer-reviewed studies on the effects of strength training on gut microbiota, indicating an open area for research. Muscle mass has previously correlated to several bacterial populations, so it's likely there's an effect. More clinical studies are needed to establish data relevant to humans and their diverse activities.[15]

Source: Dr. Peter Osborne, Gluten Free Society

Key takeaways

Gut microbiota are affected by infection, disease, diet, antibiotics, exercise, which can in turn modulate disease.

Early-life interventions have a profound effect. Beneficial effects of exercise on the gut and brain were more profound when started earlier in life.[22]

Recovery is necessary. It’s important to distinguish between physical and psychological stress in exercise, especially in endurance sports.

There is no one optimal diet because of high interindividual variability in gut microbiota, genetics, exposure, and lifestyle. Despite this, functions carried out by these microbial species appear to be the same in everyone's GI tracts.[23] Therefore, it is possible to personalize a diet that is optimal for an individual at a given time.

Gut microbiota research is still young. There are thousands of species. We're still discovering new gut bacterial species, and certain species can be beneficial in one context and opportunistic pathogens in another. Thanks to horizontal gene transfer, they can also evolve rapidly, giving rise to new strains.

We need diversity. Having a more diverse gut microbiota decreases the likelihood of illness, as they keep each other in check.

Diet still impacts gut microbiota more than exercise, but exercise can have profound effects on gut health and gut microbial composition as well.

References

1. Little, J.P., et al., Low-volume high-intensity interval training reduces hyperglycemia and increases muscle mitochondrial capacity in patients with type 2 diabetes. J Appl Physiol (1985), 2011. 111(6): p. 1554-60.

2. Campbell, S.C., et al., The Effect of Diet and Exercise on Intestinal Integrity and Microbial Diversity in Mice. PLoS One, 2016. 11(3): p. e0150502.

3. Gillen, J.B., et al., Interval training in the fed or fasted state improves body composition and muscle oxidative capacity in overweight women. Obesity (Silver Spring), 2013. 21(11): p. 2249-55.

4. Clarke, G., et al., Minireview: Gut microbiota: the neglected endocrine organ. Mol Endocrinol, 2014. 28(8): p. 1221-38.

5. Clark, A. and N. Mach, Exercise-induced stress behavior, gut-microbiota-brain axis and diet: a systematic review for athletes. J Int Soc Sports Nutr, 2016. 13: p. 43.

6. Dey, S., R.H. Singh, and P.K. Dey, Exercise training: significance of regional alterations in serotonin metabolism of rat brain in relation to antidepressant effect of exercise. Physiol Behav, 1992. 52(6): p. 1095-9.

7. Otsuka, T., et al., Effects of acute treadmill running at different intensities on activities of serotonin and corticotropin-releasing factor neurons, and anxiety- and depressive-like behaviors in rats. Behav Brain Res, 2016. 298(Pt B): p. 44-51.

8. Queipo-Ortuno, M.I., et al., Gut microbiota composition in male rat models under different nutritional status and physical activity and its association with serum leptin and ghrelin levels. PLoS One, 2013. 8(5): p. e65465.

9. Matsumoto, M., et al., Voluntary running exercise alters microbiota composition and increases n-butyrate concentration in the rat cecum. Biosci Biotechnol Biochem, 2008. 72(2): p. 572-6.

10. Hoffman-Goetz, L., N. Pervaiz, and J. Guan, Voluntary exercise training in mice increases the expression of antioxidant enzymes and decreases the expression of TNF-alpha in intestinal lymphocytes. Brain Behav Immun, 2009. 23(4): p. 498-506.

11. Monda, V., et al., Exercise Modifies the Gut Microbiota with Positive Health Effects. Oxid Med Cell Longev, 2017. 2017: p. 3831972.

12. Denou, E., et al., High-intensity exercise training increases the diversity and metabolic capacity of the mouse distal gut microbiota during diet-induced obesity. Am J Physiol Endocrinol Metab, 2016. 310(11): p. E982-93.

13. Cerda, B., et al., Gut Microbiota Modification: Another Piece in the Puzzle of the Benefits of Physical Exercise in Health? Front Physiol, 2016. 7: p. 51.

14. Estaki, M., et al., Cardiorespiratory fitness as a predictor of intestinal microbial diversity and distinct metagenomic functions. Microbiome, 2016. 4(1): p. 42.

15. Bressa, C., et al., Differences in gut microbiota profile between women with active lifestyle and sedentary women. PLoS One, 2017. 12(2): p. e0171352.

16. Clarke, S.F., et al., Exercise and associated dietary extremes impact on gut microbial diversity. Gut, 2014. 63(12): p. 1913-20.

17. Munukka, E., et al., Six-Week Endurance Exercise Alters Gut Metagenome That Is not Reflected in Systemic Metabolism in Over-weight Women. Front Microbiol, 2018. 9: p. 2323.

18. Zuhl, M., et al., Exercise regulation of intestinal tight junction proteins. Br J Sports Med, 2014. 48(12): p. 980-6.

19. de Oliveira, E.P. and R.C. Burini, The impact of physical exercise on the gastrointestinal tract. Curr Opin Clin Nutr Metab Care, 2009. 12(5): p. 533-8.

20. Musch, T.I., et al., Training effects on regional blood flow response to maximal exercise in foxhounds. J Appl Physiol (1985), 1987. 62(4): p. 1724-32.

21. Morris, G. and M. Maes, Oxidative and Nitrosative Stress and Immune-Inflammatory Pathways in Patients with Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS). Curr Neuropharmacol, 2014. 12(2): p. 168-85.

22. Mika, A., et al., Exercise is More Effective at Altering Gut Microbial Composition and Producing Stable Changes in Lean Mass in Juvenile versus Adult Male F344 Rats. PLoS One, 2015. 10(5): p. e0125889.

23. Mach, N. and D. Fuster-Botella, Endurance exercise and gut microbiota: A review. J Sport Health Sci, 2017. 6(2): p. 179-197.