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Inflammation, dysbiosis, and chronic disease

Wednesday, March 18, 2015

Speaker

Richard Flavell, Ph.D., F.R.S.
Sterling Professor and Chairman of Immunobiology
HHMI Investigator
Yale University

Dr. Flavell’s laboratory studies the molecular and cellular basis of the immune response and has discovered the role of several receptor families in the innate immune response, including Toll-like receptors and intracellular Nod-like receptor families (NLRs). His lab has established the connection between inflammasomes, microbial homeostasis and chronic diseases. He showed that dysbiosis of the microbiota leads to IBD and Metabolic Syndrome, including Obesity Fatty Liver disease and Type 2 diabetes. Most recently, his group has developed a new microbiota-profiling strategy that allows his group to identify the specific bacterial species that are involved in driving inflammatory diseases in both mice and humans; in particular, this strategy utilizes the host’s own immune response as a guide to identify specific intestinal bacteria that preferentially impact immunity and disease. 

Summary

Dysregulation of the immune system and host-microbiota interaction has been associated with the development of a variety of inflammatory as well as metabolic diseases such as obesity and diabetes. Recent studies in Dr. Flavell's laboratory have elucidated the important function of inflammasomes as steady-state sensors and regulators of the gut microbiota. Mice with a disrupted inflammasome pathway have been shown to develop a colitogenic microbial community, which results in exacerbation of chemical-induced colitis and diet-induced steatohepatitis, obesity and type 2 diabetes.

These disease phenotypes have been associated with dysbiosis resulting from the expansion of "pathobionts" which are believed to be causally driving pathogenesis. A key issue is to identify and isolate such problematic organisms. Dr. Flavell will discuss a new way that he and his colleagues have developed to identify and isolate such organisms from mice and humans. Using this approach, his lab has shown that predicted "pathobionts" from human patients with inflammatory bowel diseases (IBD) that they isolated by this approach can drive susceptibility to severe IBD in germ-free mice, whereas predicted harmless microbes from the same patients do not. These data suggest a significant involvement of such microbes in human disease.


The page was last updated on Thursday, March 26, 2015 - 6:00pm