The current goal of our research is to learn enough about the physiology and ecology of microbes and microbial communities in the gut that we are able to engineer the gut microbiome to improve human health. The first target of our engineering is the production of butyrate – a common fermentation product of some gut microbes that is essential for human health. Butyrate is the preferred energy source for mitochondria in the epithelial cells lining the gut and it also regulates their gene expression.
One of the most effective ways to influence the composition and metabolism of the gut microbiota is through diet. In an interventional study, we have tracked responses in the composition and fermentative metabolism of the gut microtiota in >800 healthy individuals. Emerging patterns suggest several configurations of the microbiome that can result in increased production of butyrate acid. We have isolated the microbes that form an anaerobic food web to convert dietary fiber to butyrate and continue to make discoveries about their physiology and interactions. Based on these results, we have initiated a clinical trial in which we are hoping to prevent the development of Graft versus Host Disease following bone marrow transplants by managing butyrate production by the gut microbiota.
We are also beginning to track hundreds of other metabolites from the gut microbiome that may influence human health. We use metagenomes and metabolomes to identify patterns that link the microbiota with their metabolites and then test those models in human organoids and gnotobiotic mice colonized with synthetic communities of microbes. This blend of wet-lab research in basic microbiology, data science and in ecology is moving us closer to engineering the gut microbiome to improve human health.