Biochemical Mechanisms of Pathogen Restriction by Intestinal Bacteria

The intestine is a highly complex ecosystem where many bacterial species interact with each other and host cells to influence animal physiology and susceptibility to pathogens. Genomic methods have provided a broad framework for understanding how alterations in microbial communities are associated with host physiology and infection, but the biochemical mechanisms of specific intestinal bacterial species are only emerging. In this review, we focus on recent studies that have characterized the biochemical mechanisms by which intestinal bacteria interact with other bacteria and host pathways to restrict pathogen infection. Understanding the biochemical mechanisms of intestinal microbiota function should provide new opportunities for therapeutic development towards a variety of infectious diseases. Intestinal bacteria can directly antagonize enteric pathogens by competing for resources, producing antimicrobials, and interfering with virulence mechanisms. Intestinal bacteria also affect host physiology and immunity through metabolic regulation, modulation of local intestinal immune responses, and signaling to other tissues. A biochemical understanding of microbiota function should reveal fundamental mechanisms of host–microbe interactions and inspire new therapeutics for infectious diseases.