Genetic Control of Gut Microbial Diversity Enhances Host Resistance to Pathogenic Infections in C. elegans

Intestinal bacteria play crucial roles in maintaining host health and regulating disease. While much of the current research has focused on how changes in the gut microbiota affect various physiological functions of the host, little is known about how the host's genetic factors shape gut microbiota diversity or how gut-dominant bacteria influence host innate immunity and lifespan. In this study, we demonstrated that a mutation in the Caenorhabditis elegans ERK-encoding gene, mpk-1, promotes the enrichment of Raoultella planticola in the gut of worms, and the bacterium confers resistance to infection by the pathogenic bacterium Pseudomonas aeruginosa PA14 (PA14) in worms. Mechanistically, a compromised immune response, which is dependent on the let-60-mpk-1 pathway, promotes the colonization of R. planticola in mpk-1 mutants. Importantly, R. planticola induces autophagy, thereby enhancing nematode resistance to PA14 infection and extending its lifespan. Our findings shed light on how immune-compromised mpk-1 mutants increase colonization permissiveness and utilize R. planticola to bolster their antibacterial immunity against pathogenic P. aeruginosa, offering new insights into the regulatory mechanisms of host-microbiota interactions. These results emphasize the complex interplay between host genetics, the microbiota, and immune responses, providing potential therapeutic strategies to modulate the microbiota for improved health outcomes.