Somdutta Saha
GlaxoSmithKline, USA
Title: Computational approaches for the identification of gut microbiome modulators and immunomodulatory Metabolites
Biography
Biography: Somdutta Saha
Abstract
The human body is the habitat of trillions of microbes co-existing in a symbiotic relationship. The knowledge of the importance of this relationship has led to the opening of new avenues in scientific discoveries, exploring the co-evolution of the host-microbiome for many patho-physiological events. In this mutually beneficial association, the host provide a nutrient-rich environment for the microbiota to thrive and they, in turn, contribute to the fitness of the host through the production of certain small molecules called metabolites. Recent studies suggest that these bacteria-derived metabolites interact with specific human gut receptors and have immuno-modulatory properties. These chemical messengers initiate a cascade of mechanistic events in the host and are imperative to linking this to phenotypic changes under disease conditions. However, the full extent of cross-talk networks is still poorly understood. In order to elucidate potential crosstalk networks, we searched the GSK pharmaceutical collection of ~4 million compounds with the chemical structures of 10 known bacterial metabolites or substrates and looked for significant activity against ~150 human receptors from associated in-house assay information. The metabolite-like compounds revealed novel mechanistic insight for microbial metabolites utilizing the notion of structural similarity to infer mechanistic principles for microbial metabolite classes. Our investigations revealed both known metabolite-receptor interactions as well as novel pathways for further study. Such metabolite-mimic drugs are potentially highly tolerable in the human system. Aassessing the functional activities of candidate metabolite mimics in phenotypic in vitro assays and in vivo models relevant to immune and metabolic-related diseases is in progress.