The Microbiome

New sequencing tools and experimental approaches have brought novel insights into the mechanisms behind autoinflammatory processes. Indeed, it is now possible to find and identify thousands of bacteria (and their function), providing an unprecedented level of detail never before witnessed. Animal models of RA have shown the capacity of specific commensal bacteria to activate proinflammatory cells, which in turn initiate and perpetuate deleterious effects in the joint. The clinical implications of these discoveries, along with the idea that humans harbor distinct enterotypes, open a new perspective in rheumatic and autoimmune research. Well-characterized studies utilizing DNA-parallel sequencing, shotgun analyses, and animal models to elucidate possible dysbiosis states in RA and related conditions are in early stages.²³

If a distinct microbiota or enterotype is identified, it would then be possible to speculate whether a particular microbiome triggers or drives autoimmunity in genetically predisposed individuals. Identification of “pathogenic” commensal organisms could provide insights into the environmental triggers of diseases such as RA and lead to a new understanding of disease pathogenesis, perhaps leading to novel approaches for thereby. Proving causation, however, will require in-depth mechanistic studies involving “humanization” of mouse models to allow selective colonization with candidate bacteria and study of consequent host immune reaction to balance alteration. Perhaps van Leeuwenhoek’s animalcules were the answer all along.

And maybe, from time to time, the inhabitants of the microbiome, like Gulliver’s diminutive mortals described in Swift’s classic, may not tremble at the sight of such a prodigious creature.

Dr. Scher is clinical instructor of medicine at the New York University School of Medicine and director of the Microbiome Center for Rheumatology and Autoimmunity at NYU Hospital for Joint Diseases in New York. Dr. Abramson is professor of medicine and pathology and director of the division of rheumatology, New York University School of Medicine and NYU Hospital for Joint Diseases.

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