Systems and Synthetic Biology: ​“Mining human gut microbial metabolism through in vitro and in silico approaches”

Abstract: The human gut microbiome is a consequence of mutual co-evolutionary interaction between the eukaryotic and prokaryotic parts of the mammalian holobiont. Based on the environmental and dietary inputs, there is a succession of microorganisms living inside the human colon. They have evolved to perform metabolic tasks that are not possible by the human host — for example, they breakdown complex polysaccharides and produce bioactive molecules such as short-chain fatty acids. They have the potential to transform human generated metabolites (e.g., primary bile acids) to signaling compounds such as secondary bile acids. They also produce several of B-vitamins, which otherwise human host derive through dietary means. Cognate receptors in various host cells could sense these bioactive metabolites and contribute to a wide variety of physiological function through signaling system in the host. An imbalance between the microbial activity and their effect on the host system could lead to the development of metabolic diseases. Provided the critical role of gut microbial metabolism, this thesis presents the evaluation of metabolic genes of gut microbiota such as bile acid, vitamin, and short-chain fatty acid metabolism using metabolic reconstructions and bioinformatics analysis in different states of health. Fecal metagenomes of subjects with inflammatory bowel diseases, type 2 diabetes and malnutrition were analyzed for such functional analyses. Furthermore, abundant gut microbial species were characterized to study their growth and metabolism in in vitro co-cultures using network analysis. The findings explained here  show the gut microbial metabolic diversity in various cohorts and conditions. It also includes a discussion on the challenges and future perspectives in a broader context of its potential application. The efforts undertaken in this work aims to inspire how the interplay between gut microbial metabolism and the host health status could contribute to the overall well-being of an individual.