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Nat Commun. 2019 Dec 11;10(1):5650. doi: 10.1038/s41467-019-13538-y.

Flagellin-elicited adaptive immunity suppresses flagellated microbiota and vaccinates against chronic inflammatory diseases.

Author information

1
Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.
2
Department of Microbiome Science, Max Planck Institute for Developmental Biology, Tübingen, Germany.
3
Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA. benoit.chassaing@inserm.fr.
4
Neuroscience Institute, Georgia State University, Atlanta, GA, USA. benoit.chassaing@inserm.fr.
5
INSERM, U1016, team "Mucosal microbiota in chronic inflammatory diseases", Paris, France. benoit.chassaing@inserm.fr.
6
Université de Paris, Paris, France. benoit.chassaing@inserm.fr.

Abstract

Alterations in gut microbiota composition are associated with metabolic syndrome and chronic inflammatory diseases such as inflammatory bowel disease. One feature of inflammation-associated gut microbiotas is enrichment of motile bacteria, which can facilitate microbiota encroachment into the mucosa and activate pro-inflammatory gene expression. Here, we set out to investigate whether elicitation of mucosal anti-flagellin antibodies by direct administration of purified flagellin might serve as a general vaccine against subsequent development of chronic gut inflammation. We show, in mice, that repeated injection of flagellin elicits increases in fecal anti-flagellin IgA and alterations in microbiota composition, reduces fecal flagellin concentration, prevents microbiota encroachment, protects against IL-10 deficiency-induced colitis, and ameliorates diet-induced obesity. Flagellin's impact on the microbiota is B-lymphocyte dependent and, in humans, obese subjects exhibit increased levels of fecal flagellin and reduced levels of fecal flagellin-specific IgA, relative to normal weight subjects. Thus, administration of flagellin, and perhaps other pathobiont antigens, may confer some protection against chronic inflammatory diseases.

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