Extracellular vesicles derived from gut microbiota, especially Akkermansia muciniphila, protect the progression of dextran sulfate sodium-induced colitis

PLoS One. 2013 Oct 24;8(10):e76520. doi: 10.1371/journal.pone.0076520. eCollection 2013.

Abstract

Gut microbiota play an important part in the pathogenesis of mucosal inflammation, such as inflammatory bowel disease (IBD). However, owing to the complexity of the gut microbiota, our understanding of the roles of commensal and pathogenic bacteria in the maintenance of immune homeostasis in the gut is evolving only slowly. Here, we evaluated the role of gut microbiota and their secreting extracellular vesicles (EV) in the development of mucosal inflammation in the gut. Experimental IBD model was established by oral application of dextran sulfate sodium (DSS) to C57BL/6 mice. The composition of gut microbiota and bacteria-derived EV in stools was evaluated by metagenome sequencing using bacterial common primer of 16S rDNA. Metagenomics in the IBD mouse model showed that the change in stool EV composition was more drastic, compared to the change of bacterial composition. Oral DSS application decreased the composition of EV from Akkermansia muciniphila and Bacteroides acidifaciens in stools, whereas increased EV from TM7 phylum, especially from species DQ777900_s and AJ400239_s. In vitro pretreatment of A. muciniphila-derived EV ameliorated the production of a pro-inflammatory cytokine IL-6 from colon epithelial cells induced by Escherichia coli EV. Additionally, oral application of A. muciniphila EV also protected DSS-induced IBD phenotypes, such as body weight loss, colon length, and inflammatory cell infiltration of colon wall. Our data provides insight into the role of gut microbiota-derived EV in regulation of intestinal immunity and homeostasis, and A. muciniphila-derived EV have protective effects in the development of DSS-induced colitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Secretion Systems / physiology*
  • Colitis / chemically induced
  • Colitis / microbiology*
  • Colitis / prevention & control*
  • Dextran Sulfate / adverse effects
  • Disease Models, Animal
  • Disease Progression
  • Female
  • Inflammatory Bowel Diseases / etiology
  • Inflammatory Bowel Diseases / microbiology
  • Inflammatory Bowel Diseases / prevention & control
  • Metagenome
  • Mice
  • Microbiota*
  • Secretory Vesicles / metabolism
  • Secretory Vesicles / ultrastructure
  • Verrucomicrobia / metabolism*

Substances

  • Bacterial Secretion Systems
  • Dextran Sulfate

Grant support

This study was supported by grants from the National Research Foundation of Korea Grant funded by the Korean Government (No. 2011-0000879 and No. 2012-0005634) and by a grant from KRIBB Research Initiative Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.