Control of Pathogens and Pathobionts by the Gut Microbiota.pdf

Control of Pathogens and Pathobionts by the Gut Microbiota Nobuhiko Kamada, Department of Pathology and Comprehensive Cancer Center, University of Michigan, Ann Arbor 48109, USA Grace Y. Chen, Department of Internal Medicine and Comprehensive Cancer Center, University of Michigan, Ann Arbor 48109, USA Naohiro Inohara, and Department of Pathology, University of Michigan, Ann Arbor 48109, USA Gabriel Nú?ez Department of Pathology and Comprehensive Cancer Center, University of Michigan, Ann Arbor 48109, USA Nobuhiko Kamada: nkamada@umich.edu; Grace Y. Chen: gchenry@umich.edu; Naohiro Inohara: ino@umich.edu; Gabriel Nú?ez: gabriel.nunez@umich.edu Abstract A dense resident microbial community in the gut, referred as the commensal microbiota, co- evolved with the host, and is essential for many host physiological processes that include enhancement of the intestinal epithelial barrier, development of the immune system, and nutrient acquisition. A major function of the microbiota is protection against colonization by pathogens and overgrowth of indigenous pathobionts that can result from the disruption of the healthy microbial community. The mechanisms that regulate the ability of the microbiota to restrain pathogen growth are complex and include competitive metabolic interactions, localization to intestinal niches, and induction of host immune responses. Pathogens, in turn, have evolved strategies to escape from commensal-mediated colonization resistance. Thus, the interplay between commensals and pathogens or indigenous pathobionts is critical for controlling infection and disease. Understanding pathogen-commensal interactions may lead to new therapeutic approaches against infectious diseases. Structural composition of the gut microbiota Vertebrates harbor a densely populated resident microbial community, which consists of bacteria, viruses, and fungi, particularly in mucosal organs, such as the oral cavity and the intestine. This internal microbial community residing wit