How exercise impacts your gut  – Part 4: Gut disease

In the first three articles of this series, I discussed how exercise beneficially impacts the gut microbiota, the gut immune system, and gut barrier function. In this article, I discuss what this means for diseases like inflammatory bowel disease, irritable bowel syndrome, SIBO, acid reflux, colon cancer, and more.

Gut diseases are increasingly prevalent.  An estimated 60 to 70 million Americans are affected by a digestive diseases, amount to a whopping $97.8 billion-dollar burden on the health care system. Despite the high cost of care, most of these diseases are poorly managed by drug treatments, which also have unpleasant side effects.

In the last few articles, I discussed how regular exercise can beneficially modulate the gut microbiota, increase butyrate production, promote proper immune responses, and potentially improve gut barrier function. Given that many digestive diseases are associated with an altered gut microbiota, abnormal immune responses, and a leaky gut, exercise offers an attractive way to help prevent and treat gut disease. In this article, I’ll discuss the evidence for exercise in a few of the most common gut diseases.

Gut motility disorders

Ever had to go #2 when you were on a run? Don’t worry, it’s not just you. Exercise reduces transit time in the large intestine, so active people tend to have more regular bowel movements than sedentary people.1 Exercise also accelerates the movement of gas through the GI tract.2 In most cases, this is highly beneficial, since inactivity has been associated with chronic constipation.3

On the other hand, acute, high-intensity exercise, like long-distance running, can cause what is affectionately known as “runner’s trots”. (Yes, that is really in the scientific literature!4) This diarrhea is largely a physiologic response to exercise, however, and does not result in significant dehydration or electrolyte imbalances. It also tends to improve with fitness levels. Still, those with chronic diarrhea may want to stick to low or moderate-intensity exercise!

Irritable bowel syndrome and SIBO

Speaking of gut motility, exercise also has implications for irritable bowel syndrome (IBS). IBS is a group of signs and symptoms including abdominal pain and changes in the pattern of bowel movements. While IBS is not completely understood, most people with IBS have low motility in the small intestine.5 This is true even in many patients with diarrhea-predominant IBS (IBS-D), who have rapid motility in the large intestine.

Gut motility is important for moving bacteria down into the large intestine. During periods of fasting, contractive waves pass through the small intestine, clearing food and bacteria down into the large intestine where it belongs. Low motility disrupts this process and is a major contributing factor to small intestinal bacterial overgrowth, or SIBO. In fact, as many as 78% of IBS patients may have SIBO.6

Exercise has been shown to reduce transit time to the end of the small intestine7,8, which means better motility and, theoretically, a lower risk of SIBO and IBS. Unfortunately, no studies have yet assessed the effects of exercise on SIBO. However, its widely agreed by physician-scientists that vigorous exercise should be avoided before SIBO breath testing,9 suggesting that exercise may reduce small intestinal gas production.

Fortunately, more is known about the effects of exercise on IBS. One randomized clinical trial found that 12 weeks of counseling to increase physical activity in IBS patients led to significant improvements in IBS symptoms, quality of life, fatigue, anxiety, and depression.10 Five years later, a subset of participants was still physically active and reaping the benefits. Other studies suggest that exercise may reduce constipation11 and bloating12 in patients with IBS, possibly due to its benefits on the gut-brain axis.

GERD

Patients with GERD, or as it is more commonly known, acid reflux, are often afraid to exercise. And it’s true, vigorous exercise can exacerbate GERD, likely due to increased intra-abdominal pressure from jouncing organs and increased relaxation of the lower esophageal sphincter, the valve that lies between the stomach and esophagus.13

However, at least one prospective study suggests that low levels of exercise are protective against acid reflux:

“Physical exercise once a week was associated with a significant, 50% decreased risk of reflux when compared with individuals who never did any organized physical exercise of at least 30 minutes duration.”14

It’s therefore important that those with acid reflux continue to exercise, and simply modify the intensity so as not to exacerbate reflux.

Colon cancer

Observational studies indicate that more physically active humans also have a 24% reduced risk for colorectal cancer.15 Even after the onset of colon cancer, taking up an exercise program may improve quality of life16,17 and reduce the risk of death from the disease.18 In controlled animal studies, voluntary exercise has also been shown to reduce the number of malignant colon tumors.19,20

Why is exercise so protective against colon cancer? One possibility may be that exercise alters the microbiota to increase butyrate production. I talked about butyrate extensively in my article series on short-chain fatty acids. I’ll review the mechanism of butyrate and cancer here:

In healthy gut cells (see left side below), butyrate enters the mitochondria and ultimately results in the production of a metabolite called acetyl CoA. Special enzymes called HATs (histone acetyltransferases) take the acetyl part and add it to proteins (histones) associated with the DNA of the cell. This is an epigenetic mechanism that effectively turns ON certain genes that are responsible for cell proliferation, which helps increase cell turnover and maintains a healthy gut barrier.

In colon cancer cells, however, mitochondria don’t seem to work properly, and butyrate accumulates in the cellular space. All of this butyrate floating around inhibits enzymes called HDACs (histone deacetylases), which serve to remove acetyl groups from the DNA and turn genes off. In other words, butyrate keeps these genes ON, too. In the case of cancer cells though, the target genes are different. The net effect of butyrate accumulation in cancer cells is suppression of proliferation and cell death.21 (For a more complete explanation of this mechanism, including the basics of epigenetics, see my previous article on butyrate.)

Diverticular Disease

Did you know that approximately fifty percent of people over the age of 60 and seventy percent of people over the age of 80 have diverticulosis? Diverticulosis is a condition where the colon forms out-pockets due to weaknesses in the muscular layers of the colon wall. While it’s typically harmless, diverticula can become inflamed or bleed, a condition called diverticulitis.

The increased prevalence in the elderly may be in part due to reduced physical activity with age. Aging is associated with a more inflammatory microbiota that is less capable of producing the beneficial metabolite butyrate. Regular exercise may be able to compensate for aging-related changes in the gut microbiome by increasing abundance of beneficial butyrate-producing microbes. (Butyrate has been shown to inhibit the progression of diverticulitis.22)

Indeed, in a study of older men, those who performed regular vigorous exercise had a 40% lower risk of developing diverticulosis than those who did not perform any physical activity.23 Risk of diverticulitis, also decreases with vigorous exercise.24,25 I look forward to future studies that relate these protective effects to changes in the gut microbiota and gut barrier function.

Inflammatory Bowel Disease

People who exercise more are also less likely to get inflammatory bowel disease (IBD), a chronic inflammatory condition of the gut that includes Crohn’s disease (CD) and Ulcerative Colitis (UC). For example, one study followed 549 UC patients for six months and found that higher reported levels of exercise were associated with a 22% decreased risk of active disease.26  In another study, a 10-week mind-body therapy intervention that included moderate exercise and a Mediterranean diet significantly improved quality of life in mildly active UC patients.

In part 1 of this article series, I talked about a study that suggests that voluntary wheel running and forced treadmill running have different effects on the gut microbiota. Other studies performed in our lab have shown that, in a mouse model of colitis, voluntary wheel running reduces mortality and confers protection, while forced treadmill running exacerbates symptoms and shortens lifespan.27

This was a novel finding, and one we were eager to follow up on. We wondered: is the altered gut microbiota in voluntary wheel running what is protecting the gut from colitis? To answer this question, my colleague, Jacob Allen, allowed one group of mice to exercise freely on a wheel for 8 weeks and one group to remain sedentary. He then collected samples from the gut of these donor mice and performed a fecal transplant into germ-free mice, which are raised in sterile incubators and have never seen a microbe in their life. The results? When the recipient mice were later subjected to an acute colitis challenge, those that had received an “exercised” microbiota were more protected than those that had received a “sedentary” microbiota.28

These results were exciting, and justify further studies in humans. As part of my dissertation research, I hope to pilot a clinical trial looking at the effects of six weeks of exercise on the gut microbiota, gut inflammation, and clinical symptoms in patients with ulcerative colitis. More than ever, we need lifestyle and root cause medicine that seeks to address the underlying cause of disease, rather than treating the symptoms. Hopefully these past four articles have convinced you that exercise will play a key role!

That’s the end of this article series on exercise and the gut! If you liked this article, be sure to subscribe to my weekly newsletter for blog and research updates.

Sources:

  1. Song, B. K., Cho, K. O., Jo, Y., Oh, J. W. & Kim, Y. S. Colon transit time according to physical activity level in adults. J. Neurogastroenterol. Motil. 18, 64–69 (2012).
  2. Dainese, R., Serra, J., Azpiroz, F. & Malagelada, J.-R. Effects of physical activity on intestinal gas transit and evacuation in healthy subjects. Am. J. Med. 116, 536–539 (2004).
  3. Huang, R., Ho, S.-Y., Lo, W.-S. & Lam, T.-H. Physical Activity and Constipation in Hong Kong Adolescents. PLOS ONE 9, e90193 (2014).
  4. Fogoros, R. N. ‘Runner’s trots’. Gastrointestinal disturbances in runners. JAMA 243, 1743–1744 (1980).
  5. Gasbarrini, A., Lauritano, E. C., Garcovich, M., Sparano, L. & Gasbarrini, G. New insights into the pathophysiology of IBS: intestinal microflora, gas production and gut motility. Eur. Rev. Med. Pharmacol. Sci. 12 Suppl 1, 111–117 (2008).
  6. Ghoshal, U. C., Shukla, R. & Ghoshal, U. Small Intestinal Bacterial Overgrowth and Irritable Bowel Syndrome: A Bridge between Functional Organic Dichotomy. Gut Liver 11, 196–208 (2017).
  7. van Nieuwenhoven, M. A., Brouns, F. & Brummer, R.-J. M. Gastrointestinal profile of symptomatic athletes at rest and during physical exercise. Eur. J. Appl. Physiol. 91, 429–434 (2004).
  8. Strid, H., Simrén, M., Störsrud, S., Stotzer, P.-O. & Sadik, R. Effect of heavy exercise on gastrointestinal transit in endurance athletes. Scand. J. Gastroenterol. 46, 673–677 (2011).
  9. Rezaie, A. et al. Hydrogen and Methane-Based Breath Testing in Gastrointestinal Disorders: The North American Consensus. Am. J. Gastroenterol. 112, 775–784 (2017).
  10. Johannesson, E., Ringström, G., Abrahamsson, H. & Sadik, R. Intervention to increase physical activity in irritable bowel syndrome shows long-term positive effects. World J. Gastroenterol. WJG 21, 600–608 (2015).
  11. Daley, A. J. et al. The effects of exercise upon symptoms and quality of life in patients diagnosed with irritable bowel syndrome: a randomised controlled trial. Int. J. Sports Med. 29, 778–782 (2008).
  12. Villoria, A., Serra, J., Azpiroz, F. & Malagelada, J.-R. Physical activity and intestinal gas clearance in patients with bloating. Am. J. Gastroenterol. 101, 2552–2557 (2006).
  13. Meining, A. & Classen, M. The role of diet and lifestyle measures in the pathogenesis and treatment of gastroesophageal reflux disease. Am. J. Gastroenterol. 95, 2692–2697 (2000).
  14. Nilsson, M., Johnsen, R., Ye, W., Hveem, K. & Lagergren, J. Lifestyle related risk factors in the aetiology of gastro-oesophageal reflux. Gut 53, 1730–1735 (2004).
  15. Wolin, K. Y., Yan, Y., Colditz, G. A. & Lee, I.-M. Physical activity and colon cancer prevention: a meta-analysis. Br. J. Cancer 100, 611–616 (2009).
  16. Peddle, C. J., Au, H.-J. & Courneya, K. S. Associations Between Exercise, Quality of Life, and Fatigue in Colorectal Cancer Survivors. Dis. Colon Rectum 51, 1242 (2008).
  17. Courneya, K. S. et al. A randomized trial of exercise and quality of life in colorectal cancer survivors. Eur. J. Cancer Care (Engl.) 12, 347–357 (2003).
  18. Meyerhardt, J. A. et al. Physical activity and survival after colorectal cancer diagnosis. J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 24, 3527–3534 (2006).
  19. Reddy, B. S., Sugie, S. & Lowenfels, A. Effect of Voluntary Exercise on Azoxymethane-induced Colon Carcinogenesis in Male F344 Rats. Cancer Res. 48, 7079–7081 (1988).
  20. Andrianopoulos, G., Nelson, R. L., Bombeck, C. T. & Souza, G. The influence of physical activity in 1,2 dimethylhydrazine induced colon carcinogenesis in the rat. Anticancer Res. 7, 849–852 (1987).
  21. Donohoe, D. R. et al. The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation. Mol. Cell 48, 612–626 (2012).
  22. Krokowicz, L. et al. Microencapsulated sodium butyrate administered to patients with diverticulosis decreases incidence of diverticulitis—a prospective randomized study. Int. J. Colorectal Dis. 29, 387–393 (2014).
  23. Aldoori, W. H. et al. Prospective study of physical activity and the risk of symptomatic diverticular disease in men. Gut 36, 276–282 (1995).
  24. Strate, L. L., Liu, Y. L., Aldoori, W. H. & Giovannucci, E. L. Physical activity decreases diverticular complications. Am. J. Gastroenterol. 104, 1221–1230 (2009).
  25. WILLIAMS, P. T. Incident Diverticular Disease Is Inversely Related to Vigorous Physical Activity. Med. Sci. Sports Exerc. 41, 1042–1047 (2009).
  26. Jones, P. D. et al. Exercise Decreases Risk of Future Active Disease in Inflammatory Bowel Disease Patients in Remission. Inflamm. Bowel Dis. 21, 1063–1071 (2015).
  27. Cook, M. D. et al. Forced treadmill exercise training exacerbates inflammation and causes mortality while voluntary wheel training is protective in a mouse model of colitis. Brain. Behav. Immun. 33, 46–56 (2013).
  28. Allen, J. M. et al. Exercise training-induced modification of the gut microbiota persists after microbiota colonization and attenuates the response to chemically-induced colitis in gnotobiotic mice. Gut Microbes 0, 1–16 (2017).
  29. de Oliveira, E. P. & Burini, R. C. The impact of physical exercise on the gastrointestinal tract. Curr. Opin. Clin. Nutr. Metab. Care 12, 533–538 (2009).

How exercise impacts your gut  – Part 4: Gut disease

In the first three articles of this series, I discussed how exercise beneficially impacts the gut microbiota, the gut immune system, and gut barrier function. In this article, I discuss what this means for diseases like inflammatory bowel disease, irritable bowel syndrome, SIBO, acid reflux, colon cancer, and more.

Gut diseases are increasingly prevalent.  An estimated 60 to 70 million Americans are affected by a digestive diseases, amount to a whopping $97.8 billion-dollar burden on the health care system. Despite the high cost of care, most of these diseases are poorly managed by drug treatments, which also have unpleasant side effects.

In the last few articles, I discussed how regular exercise can beneficially modulate the gut microbiota, increase butyrate production, promote proper immune responses, and potentially improve gut barrier function. Given that many digestive diseases are associated with an altered gut microbiota, abnormal immune responses, and a leaky gut, exercise offers an attractive way to help prevent and treat gut disease. In this article, I’ll discuss the evidence for exercise in a few of the most common gut diseases.

Gut motility disorders

Ever had to go #2 when you were on a run? Don’t worry, it’s not just you. Exercise reduces transit time in the large intestine, so active people tend to have more regular bowel movements than sedentary people.1 Exercise also accelerates the movement of gas through the GI tract.2 In most cases, this is highly beneficial, since inactivity has been associated with chronic constipation.3

On the other hand, acute, high-intensity exercise, like long-distance running, can cause what is affectionately known as “runner’s trots”. (Yes, that is really in the scientific literature!4) This diarrhea is largely a physiologic response to exercise, however, and does not result in significant dehydration or electrolyte imbalances. It also tends to improve with fitness levels. Still, those with chronic diarrhea may want to stick to low or moderate-intensity exercise!

Irritable bowel syndrome and SIBO

Speaking of gut motility, exercise also has implications for irritable bowel syndrome (IBS). IBS is a group of signs and symptoms including abdominal pain and changes in the pattern of bowel movements. While IBS is not completely understood, most people with IBS have low motility in the small intestine.5 This is true even in many patients with diarrhea-predominant IBS (IBS-D), who have rapid motility in the large intestine.

Gut motility is important for moving bacteria down into the large intestine. During periods of fasting, contractive waves pass through the small intestine, clearing food and bacteria down into the large intestine where it belongs. Low motility disrupts this process and is a major contributing factor to small intestinal bacterial overgrowth, or SIBO. In fact, as many as 78% of IBS patients may have SIBO.6

Exercise has been shown to reduce transit time to the end of the small intestine7,8, which means better motility and, theoretically, a lower risk of SIBO and IBS. Unfortunately, no studies have yet assessed the effects of exercise on SIBO. However, its widely agreed by physician-scientists that vigorous exercise should be avoided before SIBO breath testing,9 suggesting that exercise may reduce small intestinal gas production.

Fortunately, more is known about the effects of exercise on IBS. One randomized clinical trial found that 12 weeks of counseling to increase physical activity in IBS patients led to significant improvements in IBS symptoms, quality of life, fatigue, anxiety, and depression.10 Five years later, a subset of participants was still physically active and reaping the benefits. Other studies suggest that exercise may reduce constipation11 and bloating12 in patients with IBS, possibly due to its benefits on the gut-brain axis.

GERD

Patients with GERD, or as it is more commonly known, acid reflux, are often afraid to exercise. And it’s true, vigorous exercise can exacerbate GERD, likely due to increased intra-abdominal pressure from jouncing organs and increased relaxation of the lower esophageal sphincter, the valve that lies between the stomach and esophagus.13

However, at least one prospective study suggests that low levels of exercise are protective against acid reflux:

“Physical exercise once a week was associated with a significant, 50% decreased risk of reflux when compared with individuals who never did any organized physical exercise of at least 30 minutes duration.”14

It’s therefore important that those with acid reflux continue to exercise, and simply modify the intensity so as not to exacerbate reflux.

Colon cancer

Observational studies indicate that more physically active humans also have a 24% reduced risk for colorectal cancer.15 Even after the onset of colon cancer, taking up an exercise program may improve quality of life16,17 and reduce the risk of death from the disease.18 In controlled animal studies, voluntary exercise has also been shown to reduce the number of malignant colon tumors.19,20

Why is exercise so protective against colon cancer? One possibility may be that exercise alters the microbiota to increase butyrate production. I talked about butyrate extensively in my article series on short-chain fatty acids. I’ll review the mechanism of butyrate and cancer here:

In healthy gut cells (see left side below), butyrate enters the mitochondria and ultimately results in the production of a metabolite called acetyl CoA. Special enzymes called HATs (histone acetyltransferases) take the acetyl part and add it to proteins (histones) associated with the DNA of the cell. This is an epigenetic mechanism that effectively turns ON certain genes that are responsible for cell proliferation, which helps increase cell turnover and maintains a healthy gut barrier.

In colon cancer cells, however, mitochondria don’t seem to work properly, and butyrate accumulates in the cellular space. All of this butyrate floating around inhibits enzymes called HDACs (histone deacetylases), which serve to remove acetyl groups from the DNA and turn genes off. In other words, butyrate keeps these genes ON, too. In the case of cancer cells though, the target genes are different. The net effect of butyrate accumulation in cancer cells is suppression of proliferation and cell death.21 (For a more complete explanation of this mechanism, including the basics of epigenetics, see my previous article on butyrate.)

Diverticular Disease

Did you know that approximately fifty percent of people over the age of 60 and seventy percent of people over the age of 80 have diverticulosis? Diverticulosis is a condition where the colon forms out-pockets due to weaknesses in the muscular layers of the colon wall. While it’s typically harmless, diverticula can become inflamed or bleed, a condition called diverticulitis.

The increased prevalence in the elderly may be in part due to reduced physical activity with age. Aging is associated with a more inflammatory microbiota that is less capable of producing the beneficial metabolite butyrate. Regular exercise may be able to compensate for aging-related changes in the gut microbiome by increasing abundance of beneficial butyrate-producing microbes. (Butyrate has been shown to inhibit the progression of diverticulitis.22)

Indeed, in a study of older men, those who performed regular vigorous exercise had a 40% lower risk of developing diverticulosis than those who did not perform any physical activity.23 Risk of diverticulitis, also decreases with vigorous exercise.24,25 I look forward to future studies that relate these protective effects to changes in the gut microbiota and gut barrier function.

Inflammatory Bowel Disease

People who exercise more are also less likely to get inflammatory bowel disease (IBD), a chronic inflammatory condition of the gut that includes Crohn’s disease (CD) and Ulcerative Colitis (UC). For example, one study followed 549 UC patients for six months and found that higher reported levels of exercise were associated with a 22% decreased risk of active disease.26  In another study, a 10-week mind-body therapy intervention that included moderate exercise and a Mediterranean diet significantly improved quality of life in mildly active UC patients.

In part 1 of this article series, I talked about a study that suggests that voluntary wheel running and forced treadmill running have different effects on the gut microbiota. Other studies performed in our lab have shown that, in a mouse model of colitis, voluntary wheel running reduces mortality and confers protection, while forced treadmill running exacerbates symptoms and shortens lifespan.27

This was a novel finding, and one we were eager to follow up on. We wondered: is the altered gut microbiota in voluntary wheel running what is protecting the gut from colitis? To answer this question, my colleague, Jacob Allen, allowed one group of mice to exercise freely on a wheel for 8 weeks and one group to remain sedentary. He then collected samples from the gut of these donor mice and performed a fecal transplant into germ-free mice, which are raised in sterile incubators and have never seen a microbe in their life. The results? When the recipient mice were later subjected to an acute colitis challenge, those that had received an “exercised” microbiota were more protected than those that had received a “sedentary” microbiota.28

These results were exciting, and justify further studies in humans. As part of my dissertation research, I hope to pilot a clinical trial looking at the effects of six weeks of exercise on the gut microbiota, gut inflammation, and clinical symptoms in patients with ulcerative colitis. More than ever, we need lifestyle and root cause medicine that seeks to address the underlying cause of disease, rather than treating the symptoms. Hopefully these past four articles have convinced you that exercise will play a key role!

That’s the end of this article series on exercise and the gut! If you liked this article, be sure to subscribe to my weekly newsletter for blog and research updates.

Sources:

  1. Song, B. K., Cho, K. O., Jo, Y., Oh, J. W. & Kim, Y. S. Colon transit time according to physical activity level in adults. J. Neurogastroenterol. Motil. 18, 64–69 (2012).
  2. Dainese, R., Serra, J., Azpiroz, F. & Malagelada, J.-R. Effects of physical activity on intestinal gas transit and evacuation in healthy subjects. Am. J. Med. 116, 536–539 (2004).
  3. Huang, R., Ho, S.-Y., Lo, W.-S. & Lam, T.-H. Physical Activity and Constipation in Hong Kong Adolescents. PLOS ONE 9, e90193 (2014).
  4. Fogoros, R. N. ‘Runner’s trots’. Gastrointestinal disturbances in runners. JAMA 243, 1743–1744 (1980).
  5. Gasbarrini, A., Lauritano, E. C., Garcovich, M., Sparano, L. & Gasbarrini, G. New insights into the pathophysiology of IBS: intestinal microflora, gas production and gut motility. Eur. Rev. Med. Pharmacol. Sci. 12 Suppl 1, 111–117 (2008).
  6. Ghoshal, U. C., Shukla, R. & Ghoshal, U. Small Intestinal Bacterial Overgrowth and Irritable Bowel Syndrome: A Bridge between Functional Organic Dichotomy. Gut Liver 11, 196–208 (2017).
  7. van Nieuwenhoven, M. A., Brouns, F. & Brummer, R.-J. M. Gastrointestinal profile of symptomatic athletes at rest and during physical exercise. Eur. J. Appl. Physiol. 91, 429–434 (2004).
  8. Strid, H., Simrén, M., Störsrud, S., Stotzer, P.-O. & Sadik, R. Effect of heavy exercise on gastrointestinal transit in endurance athletes. Scand. J. Gastroenterol. 46, 673–677 (2011).
  9. Rezaie, A. et al. Hydrogen and Methane-Based Breath Testing in Gastrointestinal Disorders: The North American Consensus. Am. J. Gastroenterol. 112, 775–784 (2017).
  10. Johannesson, E., Ringström, G., Abrahamsson, H. & Sadik, R. Intervention to increase physical activity in irritable bowel syndrome shows long-term positive effects. World J. Gastroenterol. WJG 21, 600–608 (2015).
  11. Daley, A. J. et al. The effects of exercise upon symptoms and quality of life in patients diagnosed with irritable bowel syndrome: a randomised controlled trial. Int. J. Sports Med. 29, 778–782 (2008).
  12. Villoria, A., Serra, J., Azpiroz, F. & Malagelada, J.-R. Physical activity and intestinal gas clearance in patients with bloating. Am. J. Gastroenterol. 101, 2552–2557 (2006).
  13. Meining, A. & Classen, M. The role of diet and lifestyle measures in the pathogenesis and treatment of gastroesophageal reflux disease. Am. J. Gastroenterol. 95, 2692–2697 (2000).
  14. Nilsson, M., Johnsen, R., Ye, W., Hveem, K. & Lagergren, J. Lifestyle related risk factors in the aetiology of gastro-oesophageal reflux. Gut 53, 1730–1735 (2004).
  15. Wolin, K. Y., Yan, Y., Colditz, G. A. & Lee, I.-M. Physical activity and colon cancer prevention: a meta-analysis. Br. J. Cancer 100, 611–616 (2009).
  16. Peddle, C. J., Au, H.-J. & Courneya, K. S. Associations Between Exercise, Quality of Life, and Fatigue in Colorectal Cancer Survivors. Dis. Colon Rectum 51, 1242 (2008).
  17. Courneya, K. S. et al. A randomized trial of exercise and quality of life in colorectal cancer survivors. Eur. J. Cancer Care (Engl.) 12, 347–357 (2003).
  18. Meyerhardt, J. A. et al. Physical activity and survival after colorectal cancer diagnosis. J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 24, 3527–3534 (2006).
  19. Reddy, B. S., Sugie, S. & Lowenfels, A. Effect of Voluntary Exercise on Azoxymethane-induced Colon Carcinogenesis in Male F344 Rats. Cancer Res. 48, 7079–7081 (1988).
  20. Andrianopoulos, G., Nelson, R. L., Bombeck, C. T. & Souza, G. The influence of physical activity in 1,2 dimethylhydrazine induced colon carcinogenesis in the rat. Anticancer Res. 7, 849–852 (1987).
  21. Donohoe, D. R. et al. The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation. Mol. Cell 48, 612–626 (2012).
  22. Krokowicz, L. et al. Microencapsulated sodium butyrate administered to patients with diverticulosis decreases incidence of diverticulitis—a prospective randomized study. Int. J. Colorectal Dis. 29, 387–393 (2014).
  23. Aldoori, W. H. et al. Prospective study of physical activity and the risk of symptomatic diverticular disease in men. Gut 36, 276–282 (1995).
  24. Strate, L. L., Liu, Y. L., Aldoori, W. H. & Giovannucci, E. L. Physical activity decreases diverticular complications. Am. J. Gastroenterol. 104, 1221–1230 (2009).
  25. WILLIAMS, P. T. Incident Diverticular Disease Is Inversely Related to Vigorous Physical Activity. Med. Sci. Sports Exerc. 41, 1042–1047 (2009).
  26. Jones, P. D. et al. Exercise Decreases Risk of Future Active Disease in Inflammatory Bowel Disease Patients in Remission. Inflamm. Bowel Dis. 21, 1063–1071 (2015).
  27. Cook, M. D. et al. Forced treadmill exercise training exacerbates inflammation and causes mortality while voluntary wheel training is protective in a mouse model of colitis. Brain. Behav. Immun. 33, 46–56 (2013).
  28. Allen, J. M. et al. Exercise training-induced modification of the gut microbiota persists after microbiota colonization and attenuates the response to chemically-induced colitis in gnotobiotic mice. Gut Microbes 0, 1–16 (2017).
  29. de Oliveira, E. P. & Burini, R. C. The impact of physical exercise on the gastrointestinal tract. Curr. Opin. Clin. Nutr. Metab. Care 12, 533–538 (2009).
By |2018-03-28T22:42:09+00:00March 28th, 2018|