T cell–mediated regulation of the microbiota protects against obesity

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 <i>Desulfovibrio</i> 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 <i>Desulfovibrio</i> 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 <i>Desulfovibrio</i>, 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.