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 David Patterson, Peter J. Turnbaugh, Ajay Chawla

Research output: Contribution to journalArticle

3 Citations (Scopus)

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

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Microbiota
Eating
Appetite Regulation
Food
Body Weight
Dysbiosis
Metabolic Diseases
Myeloid Cells
Immunoglobulin A
Insulin Resistance
Mammals
Immunity
Homeostasis
Obesity
Diet
Inflammation
Phenotype
Gastrointestinal Microbiome
Lactobacillus johnsonii
mechanistic target of rapamycin complex 1

All Science Journal Classification (ASJC) codes

  • Physiology
  • Molecular Biology
  • Cell Biology

Cite this

Chagwedera, D. N., Ang, Q. Y., Bisanz, J. E., Leong, Y. A., Ganeshan, K., Cai, J., ... Chawla, A. (2019). Nutrient Sensing in CD11c Cells Alters the Gut Microbiota to Regulate Food Intake and Body Mass. Cell Metabolism, 30(2), 364-373.e7. https://doi.org/10.1016/j.cmet.2019.05.002
Chagwedera, D. Nyasha ; Ang, Qi Yan ; Bisanz, Jordan E. ; Leong, Yew Ann ; Ganeshan, Kirthana ; Cai, Jingwei ; Patterson, Andrew David ; Turnbaugh, Peter J. ; Chawla, Ajay. / Nutrient Sensing in CD11c Cells Alters the Gut Microbiota to Regulate Food Intake and Body Mass. In: Cell Metabolism. 2019 ; Vol. 30, No. 2. pp. 364-373.e7.
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Chagwedera, DN, Ang, QY, Bisanz, JE, Leong, YA, Ganeshan, K, Cai, J, Patterson, AD, Turnbaugh, PJ & Chawla, A 2019, 'Nutrient Sensing in CD11c Cells Alters the Gut Microbiota to Regulate Food Intake and Body Mass', Cell Metabolism, vol. 30, no. 2, pp. 364-373.e7. https://doi.org/10.1016/j.cmet.2019.05.002

Nutrient Sensing in CD11c Cells Alters the Gut Microbiota to Regulate Food Intake and Body Mass. / Chagwedera, D. Nyasha; Ang, Qi Yan; Bisanz, Jordan E.; Leong, Yew Ann; Ganeshan, Kirthana; Cai, Jingwei; Patterson, Andrew David; Turnbaugh, Peter J.; Chawla, Ajay.

In: Cell Metabolism, Vol. 30, No. 2, 06.08.2019, p. 364-373.e7.

Research output: Contribution to journalArticle

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T1 - Nutrient Sensing in CD11c Cells Alters the Gut Microbiota to Regulate Food Intake and Body Mass

AU - Chagwedera, D. Nyasha

AU - Ang, Qi Yan

AU - Bisanz, Jordan E.

AU - Leong, Yew Ann

AU - Ganeshan, Kirthana

AU - Cai, Jingwei

AU - Patterson, Andrew David

AU - Turnbaugh, Peter J.

AU - Chawla, Ajay

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Y1 - 2019/8/6

N2 - 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.

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Chagwedera DN, Ang QY, Bisanz JE, Leong YA, Ganeshan K, Cai J et al. Nutrient Sensing in CD11c Cells Alters the Gut Microbiota to Regulate Food Intake and Body Mass. Cell Metabolism. 2019 Aug 6;30(2):364-373.e7. https://doi.org/10.1016/j.cmet.2019.05.002