Abstract
Until recently—to a great extent—the idea of food as medicine has been foreign to most medical professionals. Certainly, practitioners have told patients with congestive heart failure and hypertension to limit sodium intake, those with coronary heart disease to reduce cholesterol intake, and those with diabetes or prediabetes to monitor sugar and carbohydrate intake. However, food prescriptions—where food is prescribed as a medication with specific dosages and durations—have not been the norm in medical standard of care conversations. That is about to change—largely due to an increasing number of studies demonstrating the power of food in various clinical settings including new discoveries in the area of the human gut microbiome.
Speaking for myself (Dexter Shurney) regarding my work spanning 2 decades, starting at Vanderbilt University and later in the real-life setting with a large global employer, Cummins, Inc, I have witnessed the unmistakable healing power of Lifestyle Medicine—in particular Food as Medicine—to prevent, treat, and reverse disease. In my current role, I am working with my clinical colleagues to make Food as Medicine more accessible and sustainable by helping to change the food environment and enabling shared decision-making between providers and patients. Fortunately, I am not alone. A growing number of practitioners are using a lifestyle medicine approach to achieve highly impressive and undeniable results. Along with positive outcomes, perhaps the most exciting part of lifestyle medicine is what is being investigated and learned about the variety of influences and mechanisms of action at play internally. The gut microbiome’s influence on human health has recently become an area of intense interest. Not only are studies demonstrating the integral role of the gut microbiome, 1 they are also reinforcing the fact that—as with many other chronic diseases—lifestyle medicine is the answer to a healthy gut microbiome and health, in general.
The Human Microbiome
The human microbiome represents a diverse array of bacteria, archaea, fungi, protozoans, and nonliving viruses that, along with their microbial genome, contribute to the greater genetic portrait of humans. It is estimated that trillions of microbiota exist in and on the human body; more than cells that make up the body itself. In terms of sheer population, it is no wonder that the microbiota, which are part of the larger microbiome, play an enormous and in human health.
The Discovery of the Human Microbiome
In the 1880s, Austrian pediatrician Theodor Escherich discovered that Escherichia coli inhabited the intestinal flora of healthy children and children with diarrheal disease. 2 In the years that followed his discovery, scientists found a number of other microorganisms in and on the human body that impact human health in a variety of ways. Throughout the 20th century, microorganisms from the nasal passages, oral cavities, skin, GI tract, and urogenital tract were isolated and characterized as the “human microbiome.” Despite early identification, the human microbiome and its influence on human health have occurred primarily only recently risen to the forefront. What little we know seems to merely scratch the surface of what is yet to be unveiled. Although microbiome research is still in early stages, studies to date show great promise for the application of lifestyle medicine as prevention, treatment, and reversal for several microbiome-related diseases.
The Gut Microbiome
Perhaps the most exciting area of human microbiome research is the microbial population that is housed in the GI tract, and particularly the part termed the “gut” as opposed to the mouth. The gut microbiome is the ecosystem that appears to be disproportionately responsible for maintaining human health and immunity.
Trillions of microorganisms survive in our intestines in a delicate balance metabolically. The gut microbiome functions to produce vitamins and synthesize amino acids. It is also involved in bile acid biotransformation and the fermentation of nondigestible substrates into short-chain fatty acids, which further stimulates the absorption of salts and water. 3 The microbiome ensures protection from pathogenic colonization (ie, prevents harmful bacteria from setting up shop) by competing for attachment sites and nutrients as well as through its ability to produce and secrete antimicrobials. 4
Healthy gut microbiota is also essential for the development and homeostasis of the immune system. Structurally, certain bacteria in the microbiota have been shown to strengthen the mucus layer of the intestinal wall, which acts as an obstacle to the uptake of pro-inflammatory molecules and antigens. Other bacteria are involved with strengthening the tight junctions of intestinal cell wall, which is partially responsible for keeping pathogens from entering the bloodstream. 5
The gut microbiome can be influenced by a variety of factors including infant birth method, infant feeding method, age, genetics, environmental exposures, stress, hygiene, immune status, sleeping habits, zip code, diet, and medication use.
Microbiome and Human Health
The microbiome is an ecosystem within our guts, and similar to other ecosystems, certain actions threaten to throw off its sophisticated balance. Dysbiosis, or an imbalance, of this ecosystem is associated with various diseases, including obesity and mental illness, among others. 6 -8 The term points to a dysfunctional microbiota community that can be differentiated from the microbiota community associated with a healthy state. 9 Many factors can alter the ecosystem of the GI tract including antibiotic use, hygiene, psychological and physical stress, radiation, altered peristalsis, sleep, and dietary changes. 10 The exact relationship between gut dysbiosis and various disease pathogenesis is somewhat uncertain; however, it is clear that there is a bidirectional relationship between human gut dysbiosis and disease, especially diseases of inflammation. Not only does dysbiosis of the gut microbiome contribute to certain diseases, certain diseases appear to alter the gut microbiome as well, potentially increasing the risk for subsequent infections/diseases of inflammation. Recent findings have illustrated a role of microbiota dysbiosis in cardiovascular disease, irritable bowel disease, Clostridium difficile infection, and inflammatory bowel disease, 11 as well as rheumatoid arthritis, 12 colorectal cancer, 13 obesity, 14 and diabetes. 15
Obesity
Although the microbiome is established at birth and is influenced by genetics, diet and certain prescription medications such as antibiotics and proton-pump inhibitors 16 appear to play a predominant role in shaping the microbiota and promoting obesity-associated dysbiosis. 17 The Standard American Diet, for example, is low in many of the components that contribute to a healthy gut microbiome including but not limited to fiber, pre-/probiotics (found in most fibrous vegetables, fruits, whole grains, nuts, seeds, and legumes), certain vitamins and minerals, and fermented matter (eg, sauerkraut, kimchi, fermented teas, kombucha). The typical American diet is also high in overall energy, fat, certain proteins, and simple sugar, which are collectively associated with lower intestinal mucus layer thickness, lower microbial diversity, decreased antimicrobial defense, larger gaps in tight junctions, and overall increased intestinal permeability to pathogens/bacteria. 18 Populations with the healthiest and highest levels of gut microbiota eat diets rich in fruits and vegetables, plant proteins, whole grains, and healthy fats, which contain larger amounts of pre-/probiotics, fiber, vitamins and minerals, antioxidants, and anti-inflammatory properties. Their gut microbiota subsequently aids in the reduction of inflammation, obesity, type 2 diabetes, 19 and cardiovascular disease.
Of particular interest in the gut microbiome research is its connection to obesity and comorbid conditions. Much research has been done to understand the connection between the ecosystem of the gut and obesity, but cause-and-effect relationships remain somewhat unclear. What is known is that obesity, as opposed to leanness, is associated with phylum-level changes in the microbiota, reduced bacterial diversity, and altered representation of bacterial genes and metabolic pathways, including those involved in nutrient harvest. 20 Variations in the microbiome can also alter metabolic responses to foods and dietary patterns, which may play a role in obesity.
The primary cause of obesity is energy intake of the host that exceeds energy expenditure. An intriguing hypothesis of how the gut bacteria may also play a role in obesity stems from studies that show that individuals with microbiomes that are more efficient at extracting energy from the diet or that promote adiposity through manipulation of host genes and metabolism are predisposed to obesity. This theory expects obese and lean individuals to have distinct microbiotas, with measurable differences in energy extraction and fat deposition from diet. 20
Another theory of how the gut microbiome contributes to obesity is through the gut microbiome’s influence on the host’s appetite and eating behaviors. Both human and animal research has found links between specific species of microbes and increased intake of nutrients that those microbes prefer, meaning that specific cravings and feelings of hunger could possibly be due to the microbes that populate the gut and not the host themselves. The metabolites that our microbes produce and the neurochemicals that they influence also impact secretions of satiety-promoting hormones. This may explain how certain eating patterns—both healthy and unhealthy—may not only populate the gut with a specific set of microbes but that those microbes may promote certain eating patterns of the host through cravings and/or hunger/satiety signaling. It is suspected that through similar pathways, microbes can also influence taste, smell, thoughts, impulsivity, and compulsivity about food. 18 This microbial influence, along with biological food-seeking predispositions, neurotransmitter reward systems, food environment, marketing, and social factors, may contribute to the difficulties that obese and/or overweight humans find in making eating-related habit and behavior changes.
The Gut–Brain Connection
We have known for many years that human nutrition has a strong impact on the development and functioning of the brain. Nutritional mechanisms and their effect on the brain show that they are involved in almost every facet of neurological functioning, including alterations in neurogenesis, neurotrophic factors, neural pathways, and neuroplasticity. Since nutrition has such a strong impact on neurological functioning, it makes sense that gut health, or lack thereof, would also interplay closely with brain health and functioning.
There is now mounting evidence that shows a bidirectional relationship of the gut microbiome and the central nervous system. This connection between the gut and the brain is known as the gut–brain axis, which has more recently been found to extend beyond these 2 systems into the endocrine, neural, and immune pathways. 21 Although there is still much to learn about how a gut microbiome–directed intervention might impact the cognitive functioning and behavior of individuals, interventions involving the gut–brain axis are seen as potential new strategies for addressing a multitude of mental health issues, including depression, anxiety, Parkinson, Attention-Deficit/Hyperactivity Disorder, and Alzheimer disease. 22 Robust preclinical animal research is available in this area, but there remains a lack of clinical human data to support any causal relationships or definitive treatments. Nevertheless, there is promise that modulating the gut microbiome via dietary changes, prebiotics and probiotics, and fecal transplantations may improve several mental health issues. 22
Food as Medicine
The microbiome is unique to each person, and parts of it are constantly evolving depending greatly on the lifestyle of the host. A healthy gut microbiota is achieved largely by increasing the ratio of “good” bacteria, which can be done in a variety of ways.
Arguably the easiest, most cost-effective, and powerful method of improving the gut microbiome is through manipulating the diet of the host. Diet is a particularly important factor in determining the microbiota composition of the gut, and the microbiome has been shown to change rapidly in response to dietary changes. 23 In other words, food truly is medicine for promoting and maintaining a healthy microbiome.
Some foods humans consume that are most beneficial to the gut microbiome have been categorized as prebiotic and probiotic foods. Prebiotics are nondigestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon and thus improve host health. 24 These are essentially the foods that feed and nourish the good bacteria in the gut. In general, eating high-fiber plant-based foods is a good foundation for a prebiotic-rich diet. Some foods that have been shown to be particularly helpful in improving the gut microbiome include asparagus, artichokes, onions, garlic, leeks, oatmeal, bananas, chicory root, cruciferous vegetables, and beans. 25
In addition to feeding a healthy gut flora, both soluble and insoluble dietary fibers found in plant-based foods are important for reducing the risk of chronic disease. Properties of dietary fiber, such as fermentability and viscosity, are thought to be important driving factors. Other compounds in foods containing dietary fiber, such as flavonoids, may also modulate the gut microbiota. 26 Higher intakes of dietary fiber reduce the risk of developing several chronic diseases, such as cardiovascular disease, type 2 diabetes, and some cancers, and have been associated with lower body weights. Moreover, population studies indicate that groups who consume more dietary fiber have less chronic disease. Perhaps this protection from chronic disease can be explained by the fact that fiber-rich prebiotic foods contain antioxidants, anti-inflammatory factors, phytonutrients, vitamins, minerals, and water—all of which have a variety of health benefits and disease-fighting potential.
Probiotics are live, active microorganisms that when ingested help maintain or alter the GI flora in ways that benefit health. In the gut, probiotics compete with harmful bacteria for adhesion sites to either rid the body of pathogens or increase the host’s immune system. Benefits of probiotics were first recognized when people started eating fermented foods. Examples of probiotic rich foods include sauerkraut, fermented vegetables, miso, tempeh, kimchi, kefir, green olives, wine, natto, sourdough bread, pickles, and kombucha. 27
The potential benefits of probiotics are widespread, but to date, there is no standardized application for practice. The umbrella of probiotics includes hundreds of species of bacteria with even more strains, each performing a specific function or having a benefit when applied alone and/or in combination with another strain. The most commonly researched probiotic genera include Lactobacillus, Bifidobacterium, and Streptococcus along with yeast varieties that include Saccharomyces boulardii. 27 Strains of Lactobacillus have demonstrated to improve health in a variety of ways including but not limited to helping certain vaginal conditions, treating diarrhea, boosting immunity, improving anxiety and depression, reducing infection risk, improving psychological health, improving symptoms of autism, decreasing allergy symptoms in children, reducing inflammation, preventing dental caries, and improving neurological health. Bifidobacterium has shown to reduce inflammation through the stimulation of immune cells, improve eczema in infants, improve anxiety/depression, and reduce inflammation. Saccharomyces boulardii, found in the yeast used to make kombucha, has been used for almost 30 years to treat several GI conditions including C difficile infection and diarrhea.
Lifestyle Medicine as Treatment for Gut Dysbiosis
The concept of eating to fuel your microbiome makes rational sense, and the evidence to date on the gut microbiome adds another layer of evidence to support lifestyle medicine. As more research on the influence of the gut microbiome on psychological health and chronic diseases becomes available, new and novel intervention strategies that target specific disease states will also come to light, providing lifestyle medicine practitioners with more tools in their toolbox to educate and care for the populations they serve. Even before we know all the minute mechanisms of action related to the gut microbiome, however, we must appreciate that the long-standing fundamentals of lifestyle medicine are not likely to change: Enough is already known to corroborate the basis of our work. As lifestyle medicine practitioners, it is our duty to educate and support those with whom we work in their quest to seek healthy gut microbiomes. One of the fundamental steps in achieving that goal is consuming diets that are high fiber and prebiotic and probiotic rich. In addition, we should remind them of the benefits of stress reduction, proper sleep, and consistent physical activity for maintaining not only good gut health but good overall health.
Indeed, the prescription for improving the health of the gut microbiome and its host, as with most modern-day health ailments, points directly to lifestyle medicine.