Infection trains the microbiota for enhanced resistance to pathogens

The microbiota shields the host against infections in a process known as colonization resistance. How infections themselves shape this fundamental process remains largely unknown. Here, we show that gut microbiota from previously infected hosts display enhanced resistance to infections. This long-term functional remodeling is associated with altered bile acid metabolism leading to the expansion of taxa that utilize the sulfonic acid taurine. Notably, supplying exogenous taurine alone is sufficient to induce this alteration in microbiota function and enhance resistance. Mechanistically, taurine potentiates microbiota production of sulfide, an inhibitor of cellular respiration, which is key to host invasion by numerous pathogens. As such, pharmaceutical sequestration of sulfide perturbs microbiota composition and promotes pathogen invasion. Together, this work reveals a process, akin to the capacity of the immune system for training, by which the host can deploy taurine as a prebiotic to nourish and educate the microbiota, promoting its resistance to infection.