Systems and Synthetic Biology: “Mining human gut microbial metabolism through in vitro and in silico approaches”
Doctoral thesis, 2019
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.
in vitro co-cultures
short chain fatty acids
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
Metagenomic analysis of microbe-mediated vitamin metabolism in the human gut microbiome
BMC Genomics,; (2019)
Gut microbiota dysbiosis is associated with malnutrition and reduced plasma amino acid levels: Lessons from genome-scale metabolic modeling
Metabolic Engineering,; Vol. 49(2018)p. 128-142
In vitro co-cultures of human gut bacterial species as predicted from co-occurrence network analysis
PLoS ONE,; Vol. 13(2018)
For the evaluation of human gut microbiome, fecal samples are reasonable proxies among otherwise invasive procedures. In the past decade, large-scale efforts of culture-independent characterization of gut microbiome realized the microbial composition of a community. Current studies reveal that at a functional level, gut microbiota entails valuable resource of metabolic enzymes which are complementary to host capabilities. With the help of experimental characterization of gut microbial species, computational modeling, and bioinformatics approaches, multi-faceted datasets could be analyzed to extract biological message crucial in sustaining the host-microbiome mutualism.
From a systems biology perspective, this thesis focuses on the interplay between the host and bacterial microbiome. As a model system, fecal metagenomes from subjects with Malnutrition, Inflammatory bowel disease, and Type 2 diabetes were investigated for microbial metabolic potential as they integrate all aspects of host immunology at the interface between bacterial colonization and innate-immune-system activation. It also highlights the co-occurrence patterns between the commensal bacteria, how variation in microbiota’s metabolite production potential (such as short-chain fatty acids, amino acids, secondary bile acids, and vitamins) could contribute to multifactorial disorders.
Research findings in this thesis report three concurrent themes: first, environmental factors are pivotal drivers of species co-existence in a community; second, the metabolic potential of a community is country- and context-dependent; third, a combination and integration of in vitro multi-layered information is valuable in strengthening the computational in silico predictions.
Bioinformatics and Systems Biology
Doktorsavhandlingar vid Chalmers tekniska högskola. Ny serie: 4556
Chalmers University of Technology
Lecture Hall KC, Kemihuset, Kemigården 4
Opponent: Prof. Susanne Brix Pedersen, Technical University of Denmark (DTU), Denmark