Enhancing the Microbiome Through Diet, Sleep, and Exercise

Strategies for Altering the Microbiome

The gut microbiome, a dynamic feature of the gastrointestinal system, has the potential to dramatically influence health outcomes. Through complex interactions with the host immune system and signaling pathways, the gut microbiome can significantly influence the pathogenesis of disease states such as cancer, metabolic syndrome, inflammatory bowel disease, and nonalcoholic fatty liver disease.

Recent technological advances have vastly improved not only our understanding of the gut microbiome but also potential mechanisms through which we may confer health benefits by altering it. As what one eats partially determines the gut flora, there are very likely significant dietary effects on the gut microbiome and a likely interaction across a broad spectrum of systemic diseases. Furthermore, emerging data on factors such as sleep and exercise underline their potential role in affecting the microbiome. This review summarizes our current understanding of how microbiome health may be affected by these lifestyle factors.

Dietary Considerations

A wide range of dietary carbohydrates, including prebiotic food ingredients, fermentable fibers, and milk oligosaccharides, have been shown to produce significant changes in the intestinal microbiota. These shifts in the microbial community are often characterized by increased levels of bifidobacteria and lactobacilli. A more recent study revealed that species of Faecalibacterium, Akkermansia, and other less well studied members may also be enriched.


Investigations of clinical outcomes associated with dietary modification of the gut microbiota have shown systemic as well as specific health benefits.[1] Both prebiotic oligosaccharides comprised of a linear arrangement of simple sugars as well as fiber-rich foods containing complex carbohydrates have been clinically studied with variable benefit. However, inconsistency of response across study participants can make the outcome of dietary interventions less predictable and limit the value of making specific recommendations to individual patients.


Nondigestible food ingredients, prebiotics can beneficially affect the host by selectively stimulating the growth and/or activity of one or more bacteria in the colon. They do so via selectively fermented ingredients that can change the composition and/or activity in the gastrointestinal microflora. In order for a food to be classified as a prebiotic, it must resist gastric acidity, hydrolysis by mammalian enzymes, and absorption in the upper gastrointestinal tract, so that it is able to be fermented by the gut microbiota into short-chain fatty acids (including acetate, propionate, and butyrate) that can be used for energy. Thus, prebiotics not only can cause shifts in the microbiota by supporting growth of a particular intestinal microbiome but also serve as substrates for production of biologically active metabolites. The primary prebiotics are the inulin-type fructans oligofructose and fructo-oligosaccharides, yet there are a number of others, including the galactan galacto-oligosaccharide. Fermentation of prebiotic carbohydrates yields butyrate and other short-chain fatty acids as well as other end products that lower the local pH, stimulate mucin production by colonocytes, and induce immunomodulatory cytokines, all of which may have potential disease modulation effects.

Prebiotic fibers are often natural constituents of a variety of foods, especially whole grains, fruits, root vegetables, and legumes. Although some foods contain appreciable concentrations of these prebiotics, they are probably found too infrequently in most Western diets to contribute much fermentable fiber to the colon. Prebiotic fiber products such as psyllium have been commonly used to supplement where needed. As a practical strategy, consumption of fermentable fiber or combinations of prebiotics may enrich for a larger and more diverse population of gut microbes and should be a standard recommendation for most disease states.


In order for a live micro-organism to be classified as a probiotic, it must satisfy the following criteria: (1) exert a beneficial effect on the host; (2) be nonpathogenic and nontoxic; (3) contain a large number of viable cells; (4) be capable of survival and metabolism within the gut; (5) remain viable during storage and use; (6) have good sensory properties; and (7) be isolated from the same species as the intended host.

Probiotics have long been used as therapeutic agents for improving gastrointestinal health. Although several microbial taxa or genera have been suggested as being beneficial to the host, there is still no actual definition of what constitutes a healthy gut microbiome to a specific patient. Most available information concerns Bifidobacteriumand Lactobacillus spp; consequently, most commercially available products generally contain bacteria from one or both of these species.

Probiotics have been shown to provide a number of health benefits and can potentially be used to alter the gut microbiome and thereby treat certain gastrointestinal conditions. Within the gastrointestinal tract, probiotics play a number of functional roles, including maintaining the intestinal barrier integrity, regulating mucin secretion, controlling immunoglobulin A secretion, and producing antimicrobial peptides, which influence cytokine production. In clinical trials, probiotics have shown beneficial effects in nonalcoholic fatty liver disease and ulcerative colitis, but a favorable effect has not been consistently demonstrated to date. The combined physiologic and clinical data strongly support the continued research of probiotics as a potential therapy for manipulating the gut microbiome.

Artificial Sweeteners

Introduced over a century ago, artificial sweeteners were designed to enhance taste without the effects of caloric intake, theoretically benefiting health by weight reduction and enhanced glycemic control. These agents are commonly used in a broad array of foods, beverages, and candy designed for diabetics and those actively dieting. However, recent information shows that these formulations drive the development of glucose intolerance through induction of compositional and functional alterations to the intestinal microbiota, which in fact promote glucose intolerance.[2] These agents may therefore have directly contributed to enhancing the very obesity epidemic they were intended to combat.


Similar to other organ systems, the gastrointestinal tract operates on a 24-hour circadian schedule that anticipates and prepares for changes in the physical environment associated with day and night. These circadian rhythms regulate a number of gastrointestinal functions, ranging from gastric acid production to small intestinal nutrient absorption to colonic motility. These rhythms are also strong regulators of immunologic processes and the gut microbiome (abundance, speciation, and function), which fluctuates in accordance with their influence. This occurs via bidirectional communication between the central nervous system and an immune system and is mediated by shared signals (neurotransmitters, hormones, and cytokines [the brain-gut axis]) and direct innervations of the immune system by the autonomic nervous system.

Prolonged sleep curtailment and the accompanying stress response invoke a persistent unspecific production of proinflammatory cytokines, which results in a low-grade chronic inflammatory state. Epidemiologic studies have established the best amount of sleep to target as approximately 7 hours. This is the range that best correlates with lower prevalence of cardiovascular disease.

Recent attention has also focused on the sleep disruption-related upregulation of provocative cytokines, such as tumor necrosis factor alpha in patients with inflammatory bowel disease, which can increase the risk of inducing a disease flare or perpetuating disease activity.[3]


There has long been a connection between exercise and gut symptomatology. Exercise and fitness modulate vagal tone, which is an integral component of the brain-gut microbiome axis. With exercise contraction of skeletal muscle, there is an innate immunity enhancement created by the release of muscle-related anti-inflammatory cytokines or myokines. Additionally, there is an associated reduction of toll-like receptors (involved in many inflammatory and cancer pathways) on monocytes and macrophages. Exercise and the gut microbiome share many immunometabolic and physiologic processes that are well established in cardiovascular health and other areas beyond the gut.

Although there is an intuitive role for exercise in the prevention and treatment of gastrointestinal conditions such as irritable bowel syndrome, nonalcoholic fatty liver disease, and obesity, among others, the recommendation to include exercise and fitness is not yet standard for specific disease state management.

As the microbiota has an established role in the development and homeostasis of the gastrointestinal tract, the potential impact of exercise and fitness on the gut microbiota has attracted recent attention. However, more research is required to quantify the anti-inflammatory and metabolic effects of moderate exercise and to weigh these against the potential hazards of excessive exercise.[4]


The effects of prebiotics, probiotics, and even antibiotics on the gut microbiome will continue to remain a mainstay of investigation and will hopefully advance our knowledge of the intricacies of the gut microbiome while improving clinical outcomes. Supplemental focus on exercise and sleep function will likely have an added beneficial effect. My prediction is that enhancing our disease management protocols will require us soon to all be in the “gut microbiome business.” This will likely be directed toward “dysbiosis” management using multiple approaches, often in combination.

Exciting work from the Weizmann Institute in Israel highlights the need to develop new nutritional strategies tailored to the individual patient, whereby unique diet and exercise protocols are used to correct the microbiome.[5] In taking such an approach, we may no longer rely on empiricism or published clinical trial data but instead more accurately address each patient’s needs in order to restore microbiome balance.



  1. Krumbeck JA, Maldonado-Gomez MX, Ramer-Tait AE, Hutkins RW. Prebiotics and synbiotics: dietary strategies for improving gut health. Curr Opin Gastroenterol. 2016;32:110-119. Abstract
  2. Suez J, Korem T, Zeevi D, et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014;514:181-186. Abstract
  3. Rosselot AE, Hong CI, Moore SR. Rhythm and bugs: circadian clocks, gut microbiota, and enteric infections. Curr Opin Gastroenterol. 2016;32:7-11. Abstract
  4. Cronin O, Molloy MG, Shanahan F. Exercise, fitness, and the gut. Curr Opin Gastroenterol. 2016;32:67-73. Abstract
  5. Zeevi D, Korem T, Zmora N, et al. Personalized nutrition by prediction of glycemic responses. Cell. 2015;163:1079-1094. Abstract

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