How exercise impacts your gut – Part 1: The microbiome

The community of trillions of microbes in the gut, collectively called the gut microbiota, has connections to virtually every organ in the body. It’s a crucial part of host physiology – providing defense against pathogens, aiding in digestion, stimulating the immune system, synthesizing vitamins, and regulating host gene expression, among other roles.

Microbial dysbiosis is associated with a host of different diseases, from autoimmune disease and obesity to skin conditions and neurological diseases. Thus, there is great interest in determining ways we can manipulate the microbiome to improve human health.

When I first joined Dr. Jeff Woods’ lab at the University of Illinois, I was mostly focused on dietary strategies to improve gut health, but I found his new line of research on exercise, the gut microbiota, and gut health incredibly intriguing. Since then, I’ve had the opportunity to take part in some truly ground-breaking research, including the first human longitudinal study on exercise and the microbiome.

In this article, I’ll discuss how exercise impacts our gut microbial communities, based on studies from our laboratory and others. In the next few articles in this series, I’ll also discuss how exercise impacts gut mucosal immunity, gut barrier function, and disease outcomes.

Early-life exercise and the gut microbiota

Exercise initiated early in life may have the greatest impact on the gut microbiota. At birth, we are colonized by a certain set of microbes, and critical early experiences can shape the maturation of the gut microbiota over time. A study published in 2015 found that exercise earlier in life was able to shift the microbiota more dramatically than exercise begun in adulthood.1,2 At the phylum level, early-life exercise was able to increase Bacteroidetes and decrease Firmicutes – a pattern that is distinctly opposite from the microbial signature in obese animal models.3

Early-life exercise also increased two bacterial genera, Blautia and Anaerostipes, which are capable of producing butyrate. Butyrate is a beneficial short-chain fatty acid (SCFA) produced from the fermentation of dietary fiber. I’ve written about it extensively, including it’s immune-regulatory, anti-inflammatory, and epigenetic effects. The beneficial microbe Lactobacillus was also increased following just three days of endurance exercise.

(In this study, early-life exercise was initiated at 4 weeks of age in mice, an age equivalent to about 6 months old in humans, and was continued until adulthood. Meanwhile, the adult mice started the exercise at around 10 weeks old – an age equivalent to about 20 years old in humans.4)

Other animal studies help us understand gut responses to exercise

While it’s clear that the microbiota is perhaps most malleable during the critical early years, the gut community continues to respond to environmental stimuli throughout adulthood.

Over a dozen studies have been performed in animals to help elucidate the effects of exercise on the gut microbiota. Unfortunately, discrepancies in the animal model used and exercise protocols have made it difficult to compare findings from one study to the next.

Still, if we look at the overall pattern across studies, endurance exercise training tends to:

  • Increase microbial diversity (particularly in models of obesity)5–7
  • Increase levels of the beneficial short-chain fatty acid butyrate8
  • Increase abundance of beneficial microbial genera, such as Lactobacillus9–11 and Bifidobacterium,10,11 as well as Faecalibacterium prausnitzii,12 Lachnospiraceae spp.,6,13 and other butyrate-producers8,9,11
  • Decrease abundance of potentially pathogenic microbes, including Streptococcus.7,13

Interestingly, the gut microbiota also appears to influence athletic performance. In 2015, researchers in Taiwan discovered that mice raised in sterile conditions that do not have a microbiota (germ-free mice) performed less well on a swimming test than mice that had even a single microbial species. Mice that had a whole consortium of microbes performed the best.14

Exercise-induced changes in the gut depend on modality

Of particular interest to my lab is the effect of exercise modality on the microbiota’s response to training. There are two primary ways to study endurance exercise in animal models:

Voluntary wheel running (VWR), where the animals are provided access to a running wheel in their cage and can run as much or as little as they desire. They enjoy running and often clock in up to 7 kilometers per day. Even mice in the wild will run on wheels.

Forced treadmill running (FTR), where the animals are placed on a treadmill for anywhere between 45-90 minutes per day. This is typically more intense exercise, but is also more stressful.

In 2015, one of my colleagues, Jacob Allen, performed a study where mice received six weeks of VWR, six weeks of FTR, or six weeks of no exercise. Interestingly, there were distinct shifts in the response of the microbiota to each mode of exercise.

FTR mice had greater microbial diversity compared with VWR mice and sedentary mice, and increased abundance of the bacterial phyla Tenericutes and Proteobacteria.15 Meanwhile, VWR mice had a lower abundance of several genera, including Turcibacter and Prevotella. These differential responses of the microbiota to exercise also had interesting implications in a mouse model of colitis, which I’ll be discussing in detail in Part 4 of this series.

But what does this mean for humans? While animal models allow us to have a lot of control over factors that influence the gut, their microbiome is quite different from ours. We needed some human studies.

Active people have a different gut microbiome than sedentary people

Indeed, over the last decade, several studies have assessed the microbiota of athletes. Perhaps the most well-known is a study that compared professional rugby players to sedentary controls.16 They found that the rugby players had increased microbial diversity, including a higher abundance of Erysipelotrichaceae, and lower abundance of Lactobacillus and Bacteroides than lean controls. However, follow-up analyses suggested that the athletes’ increased protein intake could explain nearly all of the differences in microbial diversity.

Another cross-sectional study found increased levels of the beneficial bacteria Faecalibacterium prausnitzii and Akkermansia muciniphila in active women compared to controls. They also measured the length of sedentary bouts with devices called accelerometers and found that Desulfovibrioceae and Paraprevotella species were associated with the maximum time and average time per sedentary bout, respectively.17

In a study of younger adults, cardiorespiratory fitness positively correlated with increased microbial diversity and butyrate-producing bacteria.18 Another group of researchers found that an “athletic” microbiome supports a higher turnover of carbohydrates, resulting in higher fecal SCFA concentrations compared to sedentary controls.19

While all of these findings were certainly intriguing, these studies were limited by their cross-sectional design and lack of dietary controls. More active people, and especially elite athletes, tend to eat differently than sedentary people, and it’s well established that diet has a profound impact on the microbiome. The question remained: does exercise change the microbiome in humans, independent of diet?

The first longitudinal study assessing the independent effects of exercise on the gut microbiota

This was the question that my lab sought to answer, and my first major project as a graduate student. We recruited 32 adult subjects (male and female, lean and obese) who were sedentary to undergo a six-week endurance exercise program, and collected fecal samples before and after to analyze the microbiome. Before each fecal sample, the participants adhered to a strict three-day control menu that was typical of their normal diet.

Here’s what we found.20 Exercise training for 30-60 minutes, 3 times a week, for 6 weeks:

  • Resulted in no changes at the phyla level, but many changes at lower taxonomic levels
  • Made obese and lean microbiomes appear more similar. Several genera were differentially altered by exercise depending on obesity status: For example, Bacteroides decreased in lean group, but increased in the obese group; Faecalibacterium increased in the lean group, but decreased in the obese group.
  • Increased fecal butyrate and acetate levels, particularly in the lean participants, and a trend for increased propionate
  • Increased abundance of SCFA-producing bacteria, including Clostridiales, Lachnospira, Roseburia, and Faecalibacterium, particularly in lean participants. An increase in butyrate producers was significantly correlated with gains in lean mass and loss of body fat.
  • Altered 10 microbial genera in the obese group, which were significantly associated with improvements in cardiorespiratory fitness.

After the six-week period, a subset of the participants returned to their sedentary lifestyles for six weeks before providing a final fecal sample. This was to determine if the changes with exercise reverted after a washout period with no exercise.

Here’s what we found:

  • Most bacterial genera reverted to baseline. Those that were increased with exercise decreased during the washout period and vice versa.
  • Only fecal acetate remained elevated in lean participants. Butyrate and propionate declined towards baseline levels.

Overall, this study provides evidence that exercise has independent effects on the gut microbiota, which are largely erased upon return to a sedentary lifestyle. While an increase in fecal SCFA alone is not necessarily indicative of increased SCFA production (it could simply reflect reduced absorption), the increased abundance of microbes known to produce SCFAs provides support for an upregulation of beneficial SCFA production with exercise.

What about resistance exercise?

As of February 2018, no studies have yet been published on the response of the microbiota to resistance exercise. However, given the wide range of physiological adaptations that occur during strength training, it’s highly plausible that it would have an impact on the gut microbiota. Future studies in our lab and others may elucidate these connections.

That’s all for now! Did you like this article? Be sure to subscribe so you don’t miss the next few articles in this series: how exercise impacts gut mucosal immunity, gut barrier function, and diseases of the gut.

Sources:

  1. 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 10, (2015).
  2. Mika, A. & Fleshner, M. Early-life exercise may promote lasting brain and metabolic health through gut bacterial metabolites. Immunol. Cell Biol. 94, 151–157 (2016).
  3. Ley, R. E. et al. Obesity alters gut microbial ecology. Proc. Natl. Acad. Sci. U. S. A. 102, 11070–11075 (2005).
  4. Dutta, S. & Sengupta, P. Men and mice: Relating their ages. Life Sci. 152, 244–248 (2016).
  5. Denou, E., Marcinko, K., Surette, M. G., Steinberg, G. R. & Schertzer, J. D. 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. 310, E982-993 (2016).
  6. Evans, C. C. et al. Exercise prevents weight gain and alters the gut microbiota in a mouse model of high fat diet-induced obesity. PloS One 9, e92193 (2014).
  7. Petriz, B. A. et al. Exercise induction of gut microbiota modifications in obese, non-obese and hypertensive rats. BMC Genomics 15, 511 (2014).
  8. Matsumoto, M. et al. Voluntary running exercise alters microbiota composition and increases n-butyrate concentration in the rat cecum. Biosci. Biotechnol. Biochem. 72, 572–576 (2008).
  9. Batacan, R. b. et al. A gut reaction: the combined influence of exercise and diet on gastrointestinal microbiota in rats. J. Appl. Microbiol. 122, 1627–1638 (2017).
  10. Queipo-Ortuño, 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 8, e65465 (2013).
  11. Lambert, J. E. et al. Exercise training modifies gut microbiota in normal and diabetic mice. Appl. Physiol. Nutr. Metab. 40, 749–752 (2015).
  12. Campbell, S. C. et al. The Effect of Diet and Exercise on Intestinal Integrity and Microbial Diversity in Mice. PloS One 11, e0150502 (2016).
  13. Kang, S. S. et al. Diet and exercise orthogonally alter the gut microbiome and reveal independent associations with anxiety and cognition. Mol. Neurodegener. 9, 36 (2014).
  14. Hsu, Y. J. et al. Effect of intestinal microbiota on exercise performance in mice. J. Strength Cond. Res. 29, 552–558 (2015).
  15. Allen, J. M. et al. Voluntary and forced exercise differentially alters the gut microbiome in C57BL/6J mice. J. Appl. Physiol. 118, 1059–1066 (2015).
  16. Clarke, S. F. et al. Exercise and associated dietary extremes impact on gut microbial diversity. Gut 63, 1913–1920 (2014).
  17. Bressa, C. et al. Differences in gut microbiota profile between women with active lifestyle and sedentary women. PLOS ONE 12, e0171352 (2017).
  18. Estaki, M. et al. Cardiorespiratory fitness as a predictor of intestinal microbial diversity and distinct metagenomic functions. Microbiome 4, 42 (2016).
  19. Barton, W. et al. The microbiome of professional athletes differs from that of more sedentary subjects in composition and particularly at the functional metabolic level. Gut gutjnl-2016-313627 (2017). doi:10.1136/gutjnl-2016-313627
  20. Allen, J. M. et al. Exercise Alters Gut Microbiota Composition and Function in Lean and Obese Humans. Med. Sci. Sports Exerc. (2017). doi:10.1249/MSS.0000000000001495

How exercise impacts the gut – Part 1: The microbiome

The community of trillions of microbes in the gut, collectively called the gut microbiota, has connections to virtually every organ in the body. It’s a crucial part of host physiology – providing defense against pathogens, aiding in digestion, stimulating the immune system, synthesizing vitamins, and regulating host gene expression, among other roles.

Microbial dysbiosis is associated with a host of different diseases, from autoimmune disease and obesity to skin conditions and neurological diseases. Thus, there is great interest in determining ways we can manipulate the microbiome to improve human health.

When I first joined Dr. Jeff Woods’ lab at the University of Illinois, I was mostly focused on dietary strategies to improve gut health, but I found his new line of research on exercise, the gut microbiota, and gut health incredibly intriguing. Since then, I’ve had the opportunity to take part in some truly ground-breaking research, including the first human longitudinal study on exercise and the microbiome.

In this article, I’ll discuss how exercise impacts our gut microbial communities, based on studies from our laboratory and others. In the next few articles in this series, I’ll also discuss how exercise impacts gut mucosal immunity, gut barrier function, and disease outcomes.

Early-life exercise and the gut microbiota

Exercise initiated early in life may have the greatest impact on the gut microbiota. At birth, we are colonized by a certain set of microbes, and critical early experiences can shape the maturation of the gut microbiota over time. A study published in 2015 found that exercise earlier in life was able to shift the microbiota more dramatically than exercise begun in adulthood.1,2 At the phylum level, early-life exercise was able to increase Bacteroidetes and decrease Firmicutes – a pattern that is distinctly opposite from the microbial signature in obese animal models.3

Early-life exercise also increased two bacterial genera, Blautia and Anaerostipes, which are capable of producing butyrate. Butyrate is a beneficial short-chain fatty acid (SCFA) produced from the fermentation of dietary fiber. I’ve written about it extensively, including it’s immune-regulatory, anti-inflammatory, and epigenetic effects. The beneficial microbe Lactobacillus was also increased following just three days of endurance exercise.

(In this study, early-life exercise was initiated at 4 weeks of age in mice, an age equivalent to about 6 months old in humans, and was continued until adulthood. Meanwhile, the adult mice started the exercise at around 10 weeks old – an age equivalent to about 20 years old in humans.4)

Other animal studies help us understand gut responses to exercise

While it’s clear that the microbiota is perhaps most malleable during the critical early years, the gut community continues to respond to environmental stimuli throughout adulthood.

Over a dozen studies have been performed in animals to help elucidate the effects of exercise on the gut microbiota. Unfortunately, discrepancies in the animal model used and exercise protocols have made it difficult to compare findings from one study to the next.

Still, if we look at the overall pattern across studies, endurance exercise training tends to:

  • Increase microbial diversity (particularly in models of obesity)5–7
  • Increase levels of the beneficial short-chain fatty acid butyrate8
  • Increase abundance of beneficial microbial genera, such as Lactobacillus9–11 and Bifidobacterium,10,11 as well as Faecalibacterium prausnitzii,12 Lachnospiraceae spp.,6,13 and other butyrate-producers8,9,11
  • Decrease abundance of potentially pathogenic microbes, including Streptococcus.7,13

Interestingly, the gut microbiota also appears to influence athletic performance. In 2015, researchers in Taiwan discovered that mice raised in sterile conditions that do not have a microbiota (germ-free mice) performed less well on a swimming test than mice that had even a single microbial species. Mice that had a whole consortium of microbes performed the best.14

Exercise-induced changes in the gut depend on modality

Of particular interest to my lab is the effect of exercise modality on the microbiota’s response to training. There are two primary ways to study endurance exercise in animal models:

Voluntary wheel running (VWR), where the animals are provided access to a running wheel in their cage and can run as much or as little as they desire. They enjoy running and often clock in up to 7 kilometers per day. Even mice in the wild will run on wheels.

Forced treadmill running (FTR), where the animals are placed on a treadmill for anywhere between 45-90 minutes per day. This is typically more intense exercise, but is also more stressful.

In 2015, one of my colleagues, Jacob Allen, performed a study where mice received six weeks of VWR, six weeks of FTR, or six weeks of no exercise. Interestingly, there were distinct shifts in the response of the microbiota to each mode of exercise.

FTR mice had greater microbial diversity compared with VWR mice and sedentary mice, and increased abundance of the bacterial phyla Tenericutes and Proteobacteria.15 Meanwhile, VWR mice had a lower abundance of several genera, including Turcibacter and Prevotella. These differential responses of the microbiota to exercise also had interesting implications in a mouse model of colitis, which I’ll be discussing in detail in Part 4 of this series.

But what does this mean for humans? While animal models allow us to have a lot of control over factors that influence the gut, their microbiome is quite different from ours. We needed some human studies.

Active people have a different gut microbiome than sedentary people

Indeed, over the last decade, several studies have assessed the microbiota of athletes. Perhaps the most well-known is a study that compared professional rugby players to sedentary controls.16 They found that the rugby players had increased microbial diversity, including a higher abundance of Erysipelotrichaceae, and lower abundance of Lactobacillus and Bacteroides than lean controls. However, follow-up analyses suggested that the athletes’ increased protein intake could explain nearly all of the differences in microbial diversity.

Another cross-sectional study found increased levels of the beneficial bacteria Faecalibacterium prausnitzii and Akkermansia muciniphila in active women compared to controls. They also measured the length of sedentary bouts with devices called accelerometers and found that Desulfovibrioceae and Paraprevotella species were associated with the maximum time and average time per sedentary bout, respectively.17

In a study of younger adults, cardiorespiratory fitness positively correlated with increased microbial diversity and butyrate-producing bacteria.18 Another group of researchers found that an “athletic” microbiome supports a higher turnover of carbohydrates, resulting in higher fecal SCFA concentrations compared to sedentary controls.19

While all of these findings were certainly intriguing, these studies were limited by their cross-sectional design and lack of dietary controls. More active people, and especially elite athletes, tend to eat differently than sedentary people, and it’s well established that diet has a profound impact on the microbiome. The question remained: does exercise change the microbiome in humans, independent of diet?

The first longitudinal study assessing the independent effects of exercise on the gut microbiota

This was the question that my lab sought to answer, and my first major project as a graduate student. We recruited 32 adult subjects (male and female, lean and obese) who were sedentary to undergo a six-week endurance exercise program, and collected fecal samples before and after to analyze the microbiome. Before each fecal sample, the participants adhered to a strict three-day control menu that was typical of their normal diet.

Here’s what we found.20 Exercise training for 30-60 minutes, 3 times a week, for 6 weeks:

  • Resulted in no changes at the phyla level, but many changes at lower taxonomic levels
  • Made obese and lean microbiomes appear more similar. Several genera were differentially altered by exercise depending on obesity status: For example, Bacteroides decreased in lean group, but increased in the obese group; Faecalibacterium increased in the lean group, but decreased in the obese group.
  • Increased fecal butyrate and acetate levels, particularly in the lean participants, and a trend for increased propionate
  • Increased abundance of SCFA-producing bacteria, including Clostridiales, Lachnospira, Roseburia, and Faecalibacterium, particularly in lean participants. An increase in butyrate producers was significantly correlated with gains in lean mass and loss of body fat.
  • Altered 10 microbial genera in the obese group, which were significantly associated with improvements in cardiorespiratory fitness.

After the six-week period, a subset of the participants returned to their sedentary lifestyles for six weeks before providing a final fecal sample. This was to determine if the changes with exercise reverted after a washout period with no exercise.

Here’s what we found:

  • Most bacterial genera reverted to baseline. Those that were increased with exercise decreased during the washout period and vice versa.
  • Only fecal acetate remained elevated in lean participants. Butyrate and propionate declined towards baseline levels.

Overall, this study provides evidence that exercise has independent effects on the gut microbiota, which are largely erased upon return to a sedentary lifestyle. While an increase in fecal SCFA alone is not necessarily indicative of increased SCFA production (it could simply reflect reduced absorption), the increased abundance of microbes known to produce SCFAs provides support for an upregulation of beneficial SCFA production with exercise.

What about resistance exercise?

As of February 2018, no studies have yet been published on the response of the microbiota to resistance exercise. However, given the wide range of physiological adaptations that occur during strength training, it’s highly plausible that it would have an impact on the gut microbiota. Future studies in our lab and others may elucidate these connections.

That’s all for now! Did you like this article? Be sure to subscribe so you don’t miss the next few articles in this series: how exercise impacts gut mucosal immunity, gut barrier function, and diseases of the gut.

Sources:

  1. 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 10, (2015).
  2. Mika, A. & Fleshner, M. Early-life exercise may promote lasting brain and metabolic health through gut bacterial metabolites. Immunol. Cell Biol. 94, 151–157 (2016).
  3. Ley, R. E. et al. Obesity alters gut microbial ecology. Proc. Natl. Acad. Sci. U. S. A. 102, 11070–11075 (2005).
  4. Dutta, S. & Sengupta, P. Men and mice: Relating their ages. Life Sci. 152, 244–248 (2016).
  5. Denou, E., Marcinko, K., Surette, M. G., Steinberg, G. R. & Schertzer, J. D. 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. 310, E982-993 (2016).
  6. Evans, C. C. et al. Exercise prevents weight gain and alters the gut microbiota in a mouse model of high fat diet-induced obesity. PloS One 9, e92193 (2014).
  7. Petriz, B. A. et al. Exercise induction of gut microbiota modifications in obese, non-obese and hypertensive rats. BMC Genomics 15, 511 (2014).
  8. Matsumoto, M. et al. Voluntary running exercise alters microbiota composition and increases n-butyrate concentration in the rat cecum. Biosci. Biotechnol. Biochem. 72, 572–576 (2008).
  9. Batacan, R. b. et al. A gut reaction: the combined influence of exercise and diet on gastrointestinal microbiota in rats. J. Appl. Microbiol. 122, 1627–1638 (2017).
  10. Queipo-Ortuño, 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 8, e65465 (2013).
  11. Lambert, J. E. et al. Exercise training modifies gut microbiota in normal and diabetic mice. Appl. Physiol. Nutr. Metab. 40, 749–752 (2015).
  12. Campbell, S. C. et al. The Effect of Diet and Exercise on Intestinal Integrity and Microbial Diversity in Mice. PloS One 11, e0150502 (2016).
  13. Kang, S. S. et al. Diet and exercise orthogonally alter the gut microbiome and reveal independent associations with anxiety and cognition. Mol. Neurodegener. 9, 36 (2014).
  14. Hsu, Y. J. et al. Effect of intestinal microbiota on exercise performance in mice. J. Strength Cond. Res. 29, 552–558 (2015).
  15. Allen, J. M. et al. Voluntary and forced exercise differentially alters the gut microbiome in C57BL/6J mice. J. Appl. Physiol. 118, 1059–1066 (2015).
  16. Clarke, S. F. et al. Exercise and associated dietary extremes impact on gut microbial diversity. Gut 63, 1913–1920 (2014).
  17. Bressa, C. et al. Differences in gut microbiota profile between women with active lifestyle and sedentary women. PLOS ONE 12, e0171352 (2017).
  18. Estaki, M. et al. Cardiorespiratory fitness as a predictor of intestinal microbial diversity and distinct metagenomic functions. Microbiome 4, 42 (2016).
  19. Barton, W. et al. The microbiome of professional athletes differs from that of more sedentary subjects in composition and particularly at the functional metabolic level. Gut gutjnl-2016-313627 (2017). doi:10.1136/gutjnl-2016-313627
  20. Allen, J. M. et al. Exercise Alters Gut Microbiota Composition and Function in Lean and Obese Humans. Med. Sci. Sports Exerc. (2017). doi:10.1249/MSS.0000000000001495
By |2018-02-20T20:47:42+00:00February 12th, 2018|