The Microbiome: Beyond the Gut

Understanding of the world beneath—the seething, teeming microbial world that inhabits every orifice and surface of the body—has led to a whole new paradigm in the prevention and treatment of a range of diseases. Studies examining the gut microbiome led to an explosion of research that linked disruptions in the microbiota to conditions from atopy to cardiovascular disease. David A. Johnson, MD, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, predicts that over the next 20 years, the "gut microbiome effect on health and disease will become clearer. Identification of microbial dysbiosis and directed efforts to restore more normative equilibrium in microflora will transform our current approach to disease management—for gastrointestinal disease and beyond."

The Microbiome/Inflammation/Infection Link

Back in the day—pre-2000—a patient with a cough was categorized as having an infectious process or an inflammatory (ie, allergic) process. No longer. Disruptions in the microbiome are now recognized to play a pivotal role in the development of acute and chronic processes. The "microbiota hypothesis"[1] proposes that alterations in the microbiome disrupt host homeostasis and, therefore, affect disease risk in myriad ways, with manifestations ranging from alterations in immunity to changes in metabolism.

Recognizing, and learning to minimize, the many factors that can disrupt the microbiome will continue to be a focus of research. Antibiotics may be the best known of these disruptors, but numerous other environmental factors, including changes in population density, proximity to animals, pollution, and diet, are all now known to effect the transmission and maintenance of indigenous microbiota.

A Medscape reader predicted that the next two decades would bring a better "understanding of how and why microbes cause chronic inflammatory disease." Hand in hand with this improved understanding of the microbiome and its important role in maintaining health will be increased therapeutic use of bacteriophages, already widely used in agriculture,[1] that only minimally disrupt normal flora[2] in order to treat infections caused by resistant organisms.

The Microbiome/Chronic Disease Link

It is recognized that microbiota composition is altered in patients with various chronic inflammatory conditions. In addition to gastrointestinal conditions, such as Crohn disease,[3] ulcerative colitis,[4] and irritable bowel syndrome,[5] dysbiosis, or microbial imbalance, has been associated with psoriasis,[6] both type 1[7] and type 2[8] diabetes, and cardiovascular disease.[9] Dr Johnson commented that the emerging evidence strongly suggests that changes in the gut microbiota play a pivotal role in the regulation of energy homeostasis and the development and progression of obesity and its associated metabolic disorders. Myron Genel, MD, professor emeritus of pediatrics and senior research scientist at Yale Child Health Research Center, speculated that potential therapeutic interventions would be developed "on the basis of a better understanding of the pathophysiologic implications of microflora in body cavities." Dr Johnson added that although it appears that manipulation of the gut flora may be an avenue for potential new targeted therapies, further studies are necessary before introducing them into standard clinical practice. The hope is that this enhanced understanding will finally begin to yield results that will improve the management of chronic disorders, autoimmune disease, allergy, and even dental disease in the decades to come.

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