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Cell. 2019 Oct 17;179(3):644-658.e13. doi: 10.1016/j.cell.2019.09.028. Epub 2019 Oct 10.

Segmented Filamentous Bacteria Prevent and Cure Rotavirus Infection.

Author information

1
Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.
2
Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.
3
Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
4
Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
5
Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, USA.
6
Department of Microbiology and Immunology, Oregon Health Sciences University, Portland, OR, USA.
7
Department of Pediatrics, University of Pittsburgh School of Medicine and UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
8
Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA; Neuroscience Institute, GSU, Atlanta, GA, USA.
9
Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA. Electronic address: agewirtz@gsu.edu.

Abstract

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.

KEYWORDS:

fecal transplant; germ-free mice; infectious diarrhea; microbiota-virus interactions; rotavirus; segmented filamentous bacteria; viral gastroenteritis

PMID:
31607511
DOI:
10.1016/j.cell.2019.09.028

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