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


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.

SUBMITTER: Chagwedera DN 

PROVIDER: S-EPMC6687538 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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

Chagwedera D Nyasha DN   Ang Qi Yan QY   Bisanz Jordan E JE   Leong Yew Ann YA   Ganeshan Kirthana K   Cai Jingwei J   Patterson Andrew D AD   Turnbaugh Peter J PJ   Chawla Ajay A  

Cell metabolism 20190523 2


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<sup>+</sup> myeloid cells (Tsc1<sup>f/f</sup>CD11c<sup>Cre</sup> mice) reduced food intake and body mass in the absence of metabolic disease. Co-housing and fecal transplant experiments reve  ...[more]

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