Genomic and functional diversity of cholesterol metabolism by human gut microbes

• Applicant: Professorin Dr. Mathilde Poyet
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms ; Microbial Ecology and Applied Microbiology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 564414829

The human gut microbiome is associated with comorbidities of cardiovascular diseases, such as Type 2 diabetes and obesity, which are linked to perturbations in lipid and cholesterol metabolism. Recent work showed that specific gut bacteria that are negatively associated with phenotypes of these diseases can metabolize intestinal cholesterol, suggesting a role of the gut microbiome in shaping host lipidic parameters. However, our knowledge of the scope of bacteria, genes and metabolites that are involved in the metabolism of intestinal cholesterol, and their capacity to influence host lipid levels, is limited. This project aims to illuminate the genomic and functional diversity of cholesterol metabolism by gut microbes and its impact on host physiology. Specifically, we seek to: (1) characterize cholesterol-metabolizing taxa and pathways, with a focus on Eubacterium coprostanoligenes and Oscillospiraceae species; (2) discover novel bacteria, genes, and metabolic pathways involved in cholesterol conversion; and (3) investigate how these microbial functions vary across human populations and influence host physiological outcomes such as blood cholesterol levels. To achieve these goals, we will use anaerobic culturing, genomics, metabolomics, and gnotobiology methodologies. We will leverage samples from a unique cohort and biobank, the Global Microbiome Conservancy, which contains microbial resources from worldwide human populations of differentiated lifestyles. The project will deliver novel functional annotations of taxa and genes involved in the microbial metabolism of intestinal cholesterol, and provide a deeper understanding of how the microbiome shapes host cholesterol levels and lipid metabolism.

• DFG Programme: Priority Programmes
• Subproject of: SPP 2474: Illuminating gene functions in the human gut microbiome