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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity*
  • Animals
  • Antibodies, Bacterial / immunology
  • Bacterial Vaccines / administration & dosage
  • Bacterial Vaccines / genetics
  • Bacterial Vaccines / immunology*
  • Colitis / genetics
  • Colitis / immunology
  • Colitis / microbiology
  • Colitis / prevention & control*
  • Feces / microbiology
  • Flagellin / administration & dosage
  • Flagellin / genetics
  • Flagellin / immunology*
  • Gastrointestinal Microbiome*
  • Humans
  • Immunoglobulin A / immunology
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / microbiology
  • Male
  • Mice, Inbred C57BL
  • Obesity / genetics
  • Obesity / immunology
  • Obesity / microbiology
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / immunology


  • Antibodies, Bacterial
  • Bacterial Vaccines
  • Immunoglobulin A
  • Flagellin
  • Interleukin-10