Dietary sugar silences a colonization factor in a mammalian gut symbiont

The composition of the gut microbiota is largely determined by environmental factors including the host diet. Dietary components are believed to influence the composition of the gut microbiota by serving as nutrients to a subset of microbes, thereby favoring their expansion. However, we now report that dietary fructose and glucose, which are prevalent in the Western diet, specifically silence a protein that is necessary for gut colonization, but not for utilization of these sugars, by the human gut commensal Bacteroides thetaiotaomicron. Silencing by fructose and glucose requires the 5' leader region of the mRNA specifying the protein, designated Roc for regulator of colonization. Incorporation of the roc leader mRNA in front of a heterologous gene was sufficient for fructose and glucose to turn off expression of the corresponding protein. An engineered strain refractory to Roc silencing by these sugars outcompeted wild-type B. thetaiotaomicron in mice fed a diet rich in glucose and sucrose (a disaccharide composed of glucose and fructose), but not in mice fed a complex polysacchariderich diet. Our findings underscore a role for dietary sugars that escape absorption by the host intestine and reach the microbiota: regulation of gut colonization by beneficial microbes independently of supplying nutrients to the microbiota.