Segmented filamentous bacteria prevent and cure rotavirus infection

Enteric viruses encounter epithelial cells amidst diverse microbiota. We hypothesized that our unintentional generation of rotavirus (RV)-resistant Rag1-KO mice reflected microbiota composition influencing RV infection. Accordingly, such RV-resistance was transferred by co-housing and fecal transplant. Interrogation of RV-protecting microbiotas via heat, filtration, and antimicrobial agents, followed by limiting dilution transplant to germfree mice and subsequent fecal DNA sequencing revealed a central role for segmented filamentous bacteria (SFB), which were sufficient to protect mice against RV infection and associated diarrhea. Such protection was independent of lymphocytes (innate and adaptive), interferon, IL-17, and IL-22. Colonization of ileum by SFB induced changes in host gene expression and accelerated epithelial cell turnover, which likely contributed to reducing RV burden. Yet, incubation of RV with SFB-containing feces reduced its infectivity in vitro, suggesting possible direct neutralization of RV. Thus, independent of immune cells, SFB confers protection against certain enteric viral infections and associated diarrheal disease.