Center Affiliation and Expertise: Associate Member, Inflammation and Innate Immunity Thematic Area
The major goal of my research is to understand the interaction between gut microbiota, environmental contaminant(s) and immune response and how these interactions can influence the development of diseases. Recent studies on gut microbiota suggest that microbiome and/or their metabolites play an essential role in maintaining homeostasis at mucosal as well as peripheral organs. My research program focuses on two interconnected themes: (i) to determine how environmental factors can modulate the normal gut microbiota which might result in predisposition/precipitation of diseases; and (ii) to identify gut microbiota with therapeutic ability and/or identify critical pathways in pathogenic microbiota for precision targeting without affecting the whole gut microbiota (e.g., antibiotic treatment deplete all flora). Our research group was the first in the USA to show that MS patients had distinct gut microbiota with depletion of some bacteria whereas enrichment of others (PMID: 27346372). The gut microbiota help in maintaining our health by regulating various functions, including food metabolism, energy homeostasis, maintenance of the intestinal barrier, inhibition of colonization by pathogenic organisms and shaping of both the mucosal and systemic immune responses. Alteration of the gut microbiota and resulting changes in its metabolic network perturb this homeostasis, often leading to intestinal and systemic disorders such as MS, obesity and metabolic syndrome. Our microbiome study showed that MS patients have an alteration in gut bacteria involved in the metabolism of phytoestrogens, fibers/carbohydrates, bile acids and tryptophans. Therefore, multiple projects in the laboratory are investigating the mechanism through which gut bacteria regulate host physiology, e.g., numbers of bacteria responsible for the metabolism of phytoestrogens (specifically Prevotella, Parabacteroides, and Adlercreutzia) are depleted in MS patients. As a proof of concept, we isolated Prevotella histicola from a healthy individual (one of the bacteria linked with phytoestrogen metabolism) and observed that it could induce regulatory CD4 T cells as well as suppress disease in experimental autoimmune encephalomyelitis (EAE), an animal model of MS (PMID: 28793252). Based on these two observations we are testing the hypothesis that a decrease in microbial flora associated with metabolism of plant lignan and isoflavone might be responsible for pro-inflammatory state and predisposition to disease. In another project, through a pilot funding from EHSRC, we are investigating how environmental contaminants/toxins can have an adverse impact on human health through perturbation of gut microbiota composition. In summary, my research program focuses on determining the role of gut microbiota in maintaining human health and factors (environmental, diet, and genetics) which can affect the composition of gut microbiota leading/ predisposing to the development of diseases. A better understanding of these interactions will lead to the identification of gut microbiota with therapeutic ability and/or identification of critical pathways in pathogenic microbiota for precision targeting without affecting the whole gut microbiota (e.g., antibiotic treatment deplete all flora).