IgA regulates the composition and metabolic function of gut microbiota by promoting symbiosis between bacteria

J Exp Med. 2018 Aug 6;215(8):2019-2034. doi: 10.1084/jem.20180427. Epub 2018 Jul 24.

Abstract

Immunoglobulin A (IgA) promotes health by regulating the composition and function of gut microbiota, but the molecular requirements for such homeostatic IgA function remain unknown. We found that a heavily glycosylated monoclonal IgA recognizing ovalbumin coats Bacteroides thetaiotaomicron (B. theta), a prominent gut symbiont of the phylum Bacteroidetes. In vivo, IgA alters the expression of polysaccharide utilization loci (PUL), including a functionally uncharacterized molecular family provisionally named Mucus-Associated Functional Factor (MAFF). In both mice and humans, MAFF is detected predominantly in mucus-resident bacteria, and its expression requires the presence of complex microbiota. Expression of the MAFF system facilitates symbiosis with other members of the phylum Firmicutes and promotes protection from a chemically induced model of colitis. Our data reveal a novel mechanism by which IgA promotes symbiosis and colonic homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Antibodies, Monoclonal / metabolism
  • Bacteria / genetics
  • Bacteria / metabolism*
  • Bacteroides / genetics
  • Bacteroides / physiology
  • Colon / metabolism
  • DNA-Binding Proteins
  • Female
  • Gastrointestinal Microbiome*
  • Gene Expression Regulation, Bacterial
  • Glycosylation
  • Homeostasis
  • Humans
  • Immunoglobulin A / metabolism*
  • Lipopolysaccharides / metabolism
  • MafF Transcription Factor / metabolism
  • Male
  • Mice, Inbred C57BL
  • Middle Aged
  • Models, Biological
  • Mucus / metabolism
  • Nuclear Proteins / metabolism
  • Ovalbumin / metabolism
  • Phenotype
  • Symbiosis*

Substances

  • Antibodies, Monoclonal
  • DNA-Binding Proteins
  • Immunoglobulin A
  • Lipopolysaccharides
  • MafF Transcription Factor
  • Maff protein, mouse
  • Nuclear Proteins
  • Ovalbumin