Growth effects of N-acylethanolamines on gut bacteria reflect altered bacterial abundances in inflammatory bowel disease

Nat Microbiol. 2020 Mar;5(3):486-497. doi: 10.1038/s41564-019-0655-7. Epub 2020 Jan 20.

Abstract

Inflammatory bowel diseases (IBD) are associated with alterations in gut microbial abundances and lumenal metabolite concentrations, but the effects of specific metabolites on the gut microbiota in health and disease remain largely unknown. Here, we analysed the influences of metabolites that are differentially abundant in IBD on the growth and physiology of gut bacteria that are also differentially abundant in IBD. We found that N-acylethanolamines (NAEs), a class of endogenously produced signalling lipids elevated in the stool of IBD patients and a T-cell transfer model of colitis, stimulated growth of species over-represented in IBD and inhibited that of species depleted in IBD in vitro. Using metagenomic sequencing, we recapitulated the effects of NAEs in complex microbial communities ex vivo, with Proteobacteria blooming and Bacteroidetes declining in the presence of NAEs. Metatranscriptomic analysis of the same communities identified components of the respiratory chain as important for the metabolism of NAEs, and this was verified using a mutant deficient for respiratory complex I. In this study, we identified NAEs as a class of metabolites that are elevated in IBD and have the potential to shift gut microbiota towards an IBD-like composition.

Publication types

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

MeSH terms

  • Animals
  • Bacteria / drug effects*
  • Bacteria / genetics
  • Bacteria / growth & development*
  • Bacteroidetes / drug effects
  • Bacteroidetes / isolation & purification
  • Cohort Studies
  • Disease Models, Animal
  • Dysbiosis
  • Ethanolamines / pharmacology*
  • Feces / microbiology
  • Female
  • Gastrointestinal Microbiome / drug effects*
  • Gastrointestinal Microbiome / genetics
  • Gastrointestinal Microbiome / physiology
  • Gene Expression Profiling
  • Humans
  • Inflammatory Bowel Diseases / drug therapy*
  • Inflammatory Bowel Diseases / microbiology
  • Male
  • Metagenome
  • Mice
  • Mice, Inbred C57BL
  • Microbiota / drug effects
  • Proteobacteria / drug effects
  • Proteobacteria / isolation & purification
  • Tandem Mass Spectrometry
  • Whole Genome Sequencing

Substances

  • Ethanolamines
  • N-acylethanolamines