Nutrient Sensing in CD11c Cells Alters the Gut Microbiota to Regulate Food Intake and Body Mass

D. Nyasha Chagwedera, Qi Yan Ang, Jordan E. Bisanz, Yew Ann Leong, Kirthana Ganeshan, Jingwei Cai, Andrew D. Patterson, Peter J. Turnbaugh, Ajay Chawla

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Microbial dysbiosis and inflammation are implicated in diet-induced obesity and insulin resistance. However, it is not known whether crosstalk between immunity and microbiota also regulates metabolic homeostasis in healthy animals. Here, we report that genetic deletion of tuberous sclerosis 1 (Tsc1) in CD11c+ myeloid cells (Tsc1f/fCD11cCre mice) reduced food intake and body mass in the absence of metabolic disease. Co-housing and fecal transplant experiments revealed a dominant role for the healthy gut microbiota in regulation of body weight. 16S rRNA sequencing, selective culture, and reconstitution experiments further confirmed that selective deficiency of Lactobacillus johnsonii Q1-7 contributed to decreased food intake and body mass in Tsc1f/fCD11cCre mice. Mechanistically, activation of mTORC1 signaling in CD11c cells regulated production of L. johnsonii Q1-7-specific IgA, allowing for its stable colonization in the gut. Together, our findings reveal an unexpected transkingdom immune-microbiota feedback loop for homeostatic regulation of food intake and body mass in mammals. Chagwedera et al. report that mTORC1 activation in CD11c cells reduces food intake and body weight in lean mice. The transfer of microbiota from control animals, in particular L. johnsonii Q1-7, rescues the phenotype, suggesting the existence of transkingdom immune-microbiota circuits for homeostatic regulation of food intake and body mass in response to nutrient sensing in healthy mice.

Original languageEnglish (US)
Pages (from-to)364-373.e7
JournalCell Metabolism
Volume30
Issue number2
DOIs
StatePublished - Aug 6 2019

All Science Journal Classification (ASJC) codes

  • Physiology
  • Molecular Biology
  • Cell Biology

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