Helicobacter spp. are prevalent in wild mice and protect from lethal Citrobacter rodentium infection in the absence of adaptive immunity.

Transfer of the gut microbiota from wild to laboratory mice alters the host's immune status and enhances resistance to infectious and metabolic diseases, but understanding of which microbes and how they promote host fitness is only emerging. Our analysis of metagenomic sequencing data reveals that Helicobacter spp. are enriched in wild compared with specific-pathogen-free (SPF) and conventionally housed mice, with multiple species commonly co-colonizing their hosts. We create laboratory mice harboring three non-SPF Helicobacter spp. to evaluate their effect on mucosal immunity and colonization resistance to the enteropathogen Citrobacter rodentium. Our experiments reveal that Helicobacter spp. interfere with C. rodentium colonization and attenuate C. rodentium-induced gut inflammation in wild-type (WT) mice, even preventing lethal infection in Rag2 SPF mice. Further analyses suggest that Helicobacter spp. interfere with tissue attachment of C. rodentium, putatively by reducing the availability of mucus-derived sugars. These results unveil pivotal protective functions of wild mouse microbiota constituents against intestinal infection.