The Human Microbiome

In 2011, at the Society for Integrative Oncology’s international meeting in Cleveland, Ohio, Francis Collins, PhD, head of the National Institutes of Health, shocked the audience when he asserted that although his work in the human genome was exciting, he was more impressed by the potential represented by the National Institutes of Health’s investment in the Human Microbiome Project. “This is the future,” he stated with great certainty. Surprisingly, this is also the past. More than 100 years earlier in 1908, Ilya Ilyich Metchnikov, co-winner of the 1908 Nobel Prize for Medicine, noted that “the dependence of the intestinal microbes on the food makes it possible to adapt measures to modify the flora in our bodies and to replace harmful microbes by useful microbes.”1 He coined the term dysbiosis to describe microbial ecological imbalance in the gut. What happened between 1908 and 2011? Until recently, clinicians and scientists, blinded by the discovery of antibiotics, seemingly forgot this perspective. And the bacteria that make up the human microbiome could not be cultured outside the gut using classical microbiological techniques. Moreover, one cannot grow the human microbiome in a Petri dish— the relationships are too complex and interdependent. However, researchers are now able to identify bacterial species without culture through the eyes of highthroughput screening that can catalogue million of sequences at a time looking for ribosomal RNA segments specific for bacteria (16S rRNA). Supercomputers can manage and analyze the immense data generated. The result is that scientists are now able to describe both normal and abnormal micobiota per anatomical site on the body. And clinician researchers are now successfully transplanting new microbiota as a therapy for refractory Clostridium difficile infection.2 What we have learned may shock humans who believe in autonomy. The fact is that although we humans comprise approximately one trillion cells, our gut microbiota consists of approximately 10 to 100 times more cells. And although we humans comprise approximately 20 000 genes, our intestinal microbiome has approximately 150 times more genes. In fact, scientists can now state with irrefutable evidence that our microbiome influences our metabolism, physiology, and gene expression in multiple ways relevant to mood, energy, and immune function. We humans possess an “extended genome” and function not as autonomous beings but as a complex biologic “superorganism.”3 This revolution in understanding our microbial symbionts promises equally author affiliations