BACMETH: Bacterial methylation of the human gut microbiome in response to diet for improvement of cardiometabolic health

Obesity and metabolic disease are a global health challenge and major risk factors for cardiovascular disease. Diet is a key modifiable risk factor for cardiometabolic disease but is challenging to study partly because metabolic response to diet is highly personalised. Diet exerts a major influence on the community of microbes in the human gut, the gut microbiota, which in turn plays a key role in metabolic health and disease. Understanding the links between diet, gut microbiota, and cardiometabolic health is crucial to provide tools to tackle the obesity crisis and its clinical consequences.

Although diet-induced changes to the human gut microbiota have been identified in metabolic health and disease, our understanding of the bacterial molecular processes mediating these effects remains limited. DNA methylation of bacteria in our gut could play a key mechanistic role. Bacterial methylation has been under-explored at genome-wide scale, but recent developments in sequencing show that methylation is wide-spread, plays important roles including in regulation of bacterial gene function, and may provide a valuable stable biomarker of gene regulation.

This project will characterise human gut bacterial methylation as a novel tool to uncover molecular pathways mediating diet impacts on cardiometabolic health. The hypothesis is that diet induces changes in bacterial methylation, which have functional consequences on the intestinal environment and its microbial community, and affect human health. The workflow includes 1/ diet intervention trials, 2/ large well-characterised cohorts, and 3/ functional experiments. The project will assess if diet-induced bacterial methylation marks together with bacterial methylation signatures of cardiometabolic traits can explain the inter-individual variability in metabolic response to diet, and its downstream effect on health. These novel mechanistic insights and tools will help to promote and optimise cardiometabolic disease prevention.