Gut microbiota metabolites and chromatin regulation

Denboba Lab

Epigenetic regulators in every cell require appropriate substrates and cofactors to modify chromatin structure and function, and gut microbiota produces several metabolites that feed into this regularity mechanism. For example, folate and other B vitamins (known methyl donors) are produced by numerous bacteria in the gut, such as Bifidobacterium and Lactobacillus species. The gut bacteria not only produce these metabolites, but also compete directly with the host. For instance, choline-consuming bacteria deplete methyl-donor metabolites in the host, resulting in alterations to host global DNA methylation patterns and increased susceptibility to metabolic disease. SCFAs, major products of gut bacterial fermentation, modify the epigenetic state of cells by inhibiting histone deacetylases (HDACs) activity and promoting cellular production of acetyl coenzyme A (acetyl donor). Manipulating the gut microbiota also led to global changes in H3K27me3/H3K36me0 in the colon, liver and adipose tissues. Gut bacteria can also metabolize methionine into S-adenosylmethionine (SAM), which may influence DNA and histone methylation status in the host as the gut microbial composition changes. It is evident from these studies that gut microbiota produce several metabolites that regulate host epigenetic mechanisms. However, the mechanisms through which gut microbial communities influence mammalian epigenetic regulators remain poorly understood.

To tackle these biological questions, we combine high-throughput cell culture systems with cutting-edge culturomics methods to identify gut microbiota and their metabolites that regulate epigenetic mechanisms. We are currently investigating gut bacteria that produce substrates, cofactors, and regulators of chromatin function.

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