Segmented Filamentous Bacteria Prevent and Cure Rotavirus Infection

• Published in: Cell Vol. 179; no. 3; pp. 644 - 658.e13
• Main Authors: Shi, Zhenda, Zou, Jun, Zhang, Zhan, Zhao, Xu, Noriega, Juan, Zhang, Benyue, Zhao, Chunyu, Ingle, Harshad, Bittinger, Kyle, Mattei, Lisa M., Pruijssers, Andrea J., Plemper, Richard K., Nice, Timothy J., Baldridge, Megan T., Dermody, Terence S., Chassaing, Benoit, Gewirtz, Andrew T.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17-10-2019
• Subjects: Adaptive Immunity - genetics; Animals; Anti-Infective Agents - pharmacology; Bacteria - genetics; Bacteria - metabolism; Diarrhea - microbiology; Diarrhea - prevention & control; Diarrhea - virology; fecal transplant; Feces - microbiology; Gene Expression Regulation - genetics; germ-free mice; Humans; Ileum - microbiology; Ileum - pathology; Ileum - virology; infectious diarrhea; Interferons - genetics; Interleukin-17 - genetics; Interleukin-22; Interleukins - genetics; Intestinal Mucosa - microbiology; Intestinal Mucosa - pathology; Intestinal Mucosa - virology; Mice; Microbiota - genetics; microbiota-virus interactions; rotavirus; Rotavirus - pathogenicity; Rotavirus Infections - microbiology; Rotavirus Infections - prevention & control; Rotavirus Infections - virology; segmented filamentous bacteria; viral gastroenteritis; segmented filamentous bacteria; viral gastroenteritis; rotavirus; fecal transplant; microbiota-virus interactions; infectious diarrhea; germ-free mice
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2019.09.028

Rotavirus (RV) encounters intestinal epithelial cells amidst diverse microbiota, opening possibilities of microbes influencing RV infection. Although RV clearance typically requires adaptive immunity, we unintentionally generated RV-resistant immunodeficient mice, which, we hypothesized, reflected select microbes protecting against RV. Accordingly, such RV resistance was transferred by co-housing and fecal transplant. RV-protecting microbiota were interrogated by heat, filtration, and antimicrobial agents, followed by limiting dilution transplant to germ-free mice and microbiome analysis. This approach revealed that segmented filamentous bacteria (SFB) were sufficient to protect mice against RV infection and associated diarrhea. Such protection was independent of previously defined RV-impeding factors, including interferon, IL-17, and IL-22. Colonization of the ileum by SFB induced changes in host gene expression and accelerated epithelial cell turnover. Incubation of RV with SFB-containing feces reduced infectivity in vitro, suggesting direct neutralization of RV. Thus, independent of immune cells, SFB confer protection against certain enteric viral infections and associated diarrheal disease.
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•Some mouse colonies developed spontaneous resistance to rotavirus (RV) infection•Fecal microbial transplantation transfers RV resistance•Protection against RV was mediated by segmented filamentous bacteria (SFB)•SFB impeded RV by increasing epithelial cell turnover
A bacterium can protect against rotavirus infection in mice independent of the immune system.