Helminth infection promotes colonization resistance via type 2 immunity

Science. 2016 Apr 29;352(6285):608-12. doi: 10.1126/science.aaf3229. Epub 2016 Apr 14.

Abstract

Increasing incidence of inflammatory bowel diseases, such as Crohn's disease, in developed nations is associated with changes to the microbial environment, such as decreased prevalence of helminth colonization and alterations to the gut microbiota. We find that helminth infection protects mice deficient in the Crohn's disease susceptibility gene Nod2 from intestinal abnormalities by inhibiting colonization by an inflammatory Bacteroides species. Resistance to Bacteroides colonization was dependent on type 2 immunity, which promoted the establishment of a protective microbiota enriched in Clostridiales. Additionally, we show that individuals from helminth-endemic regions harbor a similar protective microbiota and that deworming treatment reduced levels of Clostridiales and increased Bacteroidales. These results support a model of the hygiene hypothesis in which certain individuals are genetically susceptible to the consequences of a changing microbial environment.

Publication types

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

MeSH terms

  • Animals
  • Bacteroides / immunology*
  • Bacteroides Infections / immunology*
  • Clostridiales / immunology
  • Clostridium Infections / immunology
  • Crohn Disease / genetics*
  • Crohn Disease / immunology
  • Gastrointestinal Microbiome / immunology*
  • Genetic Predisposition to Disease
  • Hygiene Hypothesis
  • Intestines / immunology*
  • Intestines / microbiology
  • Intestines / parasitology
  • Mice
  • Mice, Mutant Strains
  • Nod2 Signaling Adaptor Protein / genetics*
  • Trichuriasis / immunology*
  • Trichuris / immunology*

Substances

  • Nod2 Signaling Adaptor Protein
  • Nod2 protein, mouse