Elucidating the consequences of dietary sugar consumption on the gut microbiota

Project Summary The gut microbiota is a critical determinant of human health and development. Diets rich in the refined sugars glucose and fructose can modulate gut microbial abundance and metabolism thereby increasing disease susceptibility. However, the mechanisms governing microbial responses to dietary sugar in the gut remain poorly understood. We have demonstrated that host dietary sugar consumption silences expression of a colonization factor called Roc in Bacteroides thetaiotaomicron, an abundant gut bacterium associated with lean, healthy individuals. We determined that a conserved transcription factor is necessary to synthesize Roc and regulates additional bacterial factors that mediate critical host-microbial interactions, including an immunomodulatory protein and fucose utilization genes. We hypothesize that the activity of this transcription factor is governed by a putative intracellular metabolite that is differentially synthesized according to host diet composition and dramatically reduced upon sugar-rich diet consumption. We have identified critical molecular players governing the activity of this transcription factor and propose to 1.) elucidate the mechanisms governing its activation, 2.) determine how dietary sugar consumption silences its activity, and 3.) characterize the consequences of host sugar-rich diet consumption on microbial product synthesis in vivo. We believe that this work will reveal a conserved pathway that is disrupted by host sugar consumption resulting in aberrant gut microbial activities. Furthermore, this work has uncovered a molecular target for modulation of microbial abundance and metabolism in the host and can be exploited for rational manipulation of the gut microbiota to treat diseases.