Commentary to Accompany
It is generally accepted that the trillions of organisms residing in our intestines, their metabolic products, and effects on intestinal health are important modulators of chronic disease. As such, there is an increasing push to understand how lifestyle and other factors can be used to manipulate the microbiota for improved health outcomes. Two important modifiable factors that potentially have significant impact on the gut microbiota are diet and exercise. Although diet-microbiota interactions have been studied extensively, exercise-microbiota studies are just emerging and many questions remain to be answered. Campbell and Wisniewski (2), in a paper published in this issue, present a conceptual framework highlighting the role of exercise in stimulating microbial diversity and favorably influencing general health through microbiota-mediated interactions. They propose several mechanisms, supported by current literature, by which exercise-microbiota interactions may influence host physiology.
Evidence from animal studies supports exercise as an important factor modulating gut microbial communities. In general, exercise seems to beneficially impact the gut microbiota, although relevance of these studies to human populations is difficult to ascertain. A major challenge in determining the effects of exercise on human microbiota is uncoupling the effects of physical activity from dietary differences. For example, data from the only published human study to date indicates that athletic activity positively impacts microbial diversity and intestinal inflammation (4). However, the elite athletes participating in the study also consumed a diet that differed significantly from that of healthy sedentary individuals. In particular, the elite athletes consumed higher levels of protein, which may have been responsible for the observed effects on the gut. Another study in overweight men showed that high protein consumption and carbohydrate restriction reduced the production of beneficial short-chain fatty acids and increased the generation of carcinogenic nitrogen-containing compounds (6). This raises the provocative idea that specific dietary components affect microbial metabolism differently in active and sedentary individuals.
In the conceptual model they present, Campbell and Wisniewski (2) suggest exercise may exert unique effects on the microbiota independent of diet, possibly via reduction of inflammation in the gut. Although reduction of intestinal inflammation may play a role in microbial modulation in moderate exercise, intense exercise has well-studied negative effects on gut barrier function suggesting that beneficial microbial profiles reported in elite athletes may be modulated by other mechanisms. Exercise-induced stress reduction can influence the microbiota via the hypothalamic-pituitary-adrenal axis. The existence of a muscle-microbiota axis also has been hypothesized and is supported by studies in germ-free rats showing increased expression of 5′ adenosine monophosphate-activated protein kinase (pAMPK) and AMPK-independent fasting-inducible adipose factor, which regulate glucose uptake and lipid oxidation in muscle (1). Other mechanisms mediating exercise-microbiota interactions, including regulation of bile acids and immune modulation, have recently been reviewed (3). Determining whether exercise modulates the microbiota via these mechanisms in human populations and its relevance in the context of disease prevention is a critical step in optimizing lifestyle for improved intestinal health.
Campbell and Wisniewki (2) also discuss the exciting possibility that microbiota-exercise interactions are bidirectional and that an optimal microbial makeup could enhance exercise performance. This was demonstrated in a study showing germ-free mice reached exhaustion more quickly than animals colonized by a single bacterial species, and those with multiple nonpathogenic bacteria had the greatest endurance (5). It will be interesting to see if gut microbial profiles in humans are predictive of athletic performance. If so, this would have broad implications for sports nutrition and create markets for supplements to modify the microbiota for improved athletic performance.
Research on the relation between exercise and the microbiota is still in its infancy. Carefully designed, well-controlled human studies that minimize dietary influence on microbial populations are needed to advance this research area. How do age, sex, duration, and intensity of exercise influence its effects on the microbiota? Is there an optimum balance where exercise exerts maximum benefits on human physiology without creating detrimental effects on gut barrier? Are dietary components used differently by the gut microbiota of active and sedentary individuals? These questions and others may be the next frontier in microbiota research.
Department of Food Science and Human Nutrition
College of Health and Human Sciences
Colorado State University
Fort Collins, CO
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