T cell-mediated regulation of the microbiota protects against obesity

Science. 2019 Jul 26;365(6451):eaat9351. doi: 10.1126/science.aat9351.

Abstract

The microbiota influences obesity, yet organisms that protect from disease remain unknown. During studies interrogating host-microbiota interactions, we observed the development of age-associated metabolic syndrome (MetS). Expansion of Desulfovibrio and loss of Clostridia were key features associated with obesity in this model and are present in humans with MetS. T cell-dependent events were required to prevent disease, and replacement of Clostridia rescued obesity. Inappropriate immunoglobulin A targeting of Clostridia and increased Desulfovibrio antagonized the colonization of beneficial Clostridia. Transcriptional and metabolic analysis revealed enhanced lipid absorption in the obese host. Colonization of germ-free mice with Clostridia, but not Desulfovibrio, down-regulated genes that control lipid absorption and reduced adiposity. Thus, immune control of the microbiota maintains beneficial microbial populations that constrain lipid metabolism to prevent MetS.

Publication types

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

MeSH terms

  • Animals
  • Antibiosis
  • Clostridium / immunology*
  • Desulfovibrio / immunology*
  • Host Microbial Interactions
  • Intestinal Absorption
  • Lipid Metabolism
  • Metabolic Syndrome / immunology
  • Metabolic Syndrome / microbiology
  • Mice
  • Mice, Mutant Strains
  • Microbiota / immunology*
  • Myeloid Differentiation Factor 88 / genetics
  • Obesity / immunology*
  • Obesity / microbiology*
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88