Gut microbiota, one-carbon metabolism, epigenetic programming

Denboba Lab

Parental exposure during critical periods of vulnerability (before conception and in utero) can disrupt early life programming, presumably by altering epigenetic information. One-carbon (1C) metabolism is a vital component of early life development, serving as a nutrient sensor and integrator of the parental environment with epigenetic programming. This metabolic process provides the 1C units necessary for DNA, protein, and lipid biosynthesis and epigenetic modification in mammals. One of the key processes in 1C metabolism is the synthesis of S-adenosylmethionine (SAM), which is the source of most of the daily methyl transfer reactions in the cell.

There are several metabolic pathways involved in 1C metabolism, including folate cycle, methionine cycle, and transsulfuration pathway. Gut microbiota provides a number of micronutrients that feed into these metabolic pathways, including choline, riboflavin, folate, B12 and acetyl-CoA. Our research aims to identify and validate gut microbiota that regulate epigenetic programming through 1C metabolic pathways. Here, a combined diet-microbiome approach will be utilized to investigate the regulatory role of candidates gut bacteria or synthetic bacteria (e.g. methyl & acetyl donors) using a germ-free mouse model. In this project, we also aim to establish microbiome-induced epigenetically susceptible mouse models.