The Human Microbiome

Over the past few decades, medical researchers have begun to shine a light on a largely uncharted and complex world: the human gut. In a dizzying number of studies, the gut microbiome has been linked to clinical fields beyond gastroenterology, including immunology, oncology and diabetes. Estimates of how many microbes the human gut plays host to vary considerably, some as high as 400 trillion. It was once thought that microbes outnumber cells in the body by 10 to 1. However, this factoid was recently exposed to have been erroneously calculated in an earlier study.

The microbiome is composed primarily of bacteria but also archaea (single-cell organisms), fungi, viruses, and protozoa, and its delicate ecologic balance has given rise to the theory that modern hygienic practices (e.g. overuse of antibiotics, improved sanitation) have been detrimental to health by reducing exposure to bacteria on which humans thrived for millennia. Isolated hunter-gatherer tribes in South America actually have considerably more diverse microbiomes than people in industrialized societies. In an ironic twist, the very same progress that may be hurting us has also given us the means to unravel the reasons why – and potentially intervene to correct it.

The first theories of the microbiome’s role in maintaining health were proposed by Metchnikoff (1845-1916). A Russian scientist working in Louis Pasteur’s laboratory, Metchnikoff won a Nobel Prize in 1908 for helping to pioneer cellular and humoral immunology. Late in his life, Metchnikoff embarked on a personal quest to research methods of staving off senility and other markers of aging. Noticing that some economically- disadvantaged people nonetheless experienced longer lives, he studied their diet and lifestyle choices. This led to his theory that aging-related illnesses were the result of phagocytes being transformed from protective to destructive via bacteria in the colon. He believed that regular consumption of lactic acid bacteria in fermented dairy products would reverse this action and promote longevity, perhaps the first instance in which probiotics (the practice of introducing microorganisms for their health benefits) were offered as a medical solution.

In the first decade of the present century, multiple studies appeared in quick succession that would reshape our concept of the gut microbiome’s role in health and illness. One of the first crucial discoveries came in a 2005 gene-sequencing study of colonic samples from healthy subjects. It noted that a majority of newly-discovered microorganisms had little overlap from patient to patient and there were slight differences from place to place. A comparative study then determined that lean and obese subjects had different groupings of microbes present in their gut, and that an obese person’s profile changed upon weight loss on a lower-calorie diet, giving tangible evidence of the value of even moderate adjustments to eating habits.

One of the most interesting recent findings has been that the microbiome communicates with the brain indirectly (via hormones or the immune system) and directly (via neurotransmitters in the gut), and has been linked to several neurologic conditions. Autism spectrum disorders have a potential association with changes in the gut microbiome, while the inflammatory- state changes noted in schizophrenia and bipolar disorder indicate a similar link. This connectivity has inspired new treatments for psychological and neurologic conditions. Participants given probiotics were shown to experience a reduction in aggressive thoughts, and probiotics were observed to decrease stress in those undergoing laryngeal cancer surgery. Another study observed that long-term, broad-spectrum antibiotics decreased plaques that contribute to Alzheimer’s disease.

It should be noted that the overwhelming attention given to the microbiome has not been without critics. A review in the journal Nature expressed this concern: ‘The hype surrounding microbiome research is dangerous, for individuals who might make ill-informed decisions, and for the scientific enterprise, which needs to develop better experimental methods to generate hypotheses and evaluate conclusions.’ The article’s author also referenced companies that, similar to those conducting individual human genetic profiling, offer to provide a microbial portrait using fecal samples, and expressed concern about the varying and imprecise results that can come from such an analysis. The research community must consider the question of whether the tools pivotal to this research – the use of germ-free laboratory mice – truly reflect the real-world diversity of the human microbiome.

If the microbiome was a largely undiscovered territory twenty years ago, it is now awash with pioneers. I believe more discoveries are to come. These will draw more researchers looking to produce crucial interventions, as well as healthcare companies hoping to convert that work into healthy returns. While clinicians await proven therapeutic options, they can take steps to positively affect patients’ microbiomes, beginning with dietary and lifestyle recommendations. Although these involve re-iterating current recommendations, they now come with new robust data to back up their utility. Such established strategies include shifting patients toward fiber-rich diets, and promoting immunity and intestinal health by modifying sleep patterns.