Cell Metabolism
Volume 23, Issue 2, 9 February 2016, Pages 324-334
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Article
Gut Commensal E. coli Proteins Activate Host Satiety Pathways following Nutrient-Induced Bacterial Growth

https://doi.org/10.1016/j.cmet.2015.10.017Get rights and content
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Highlights

  • Regular nutrition stabilizes the E. coli exponential (Exp) growth for 20 min

  • E. coli proteome changes in the stationary (Stat) phase

  • Exp and Stat E. coli proteins intra-GI tract stimulate GLP-1 and PYY, respectively

  • Stat E. coli proteins i.p. activate anorexigenic neurons in the brain

Summary

The composition of gut microbiota has been associated with host metabolic phenotypes, but it is not known if gut bacteria may influence host appetite. Here we show that regular nutrient provision stabilizes exponential growth of E. coli, with the stationary phase occurring 20 min after nutrient supply accompanied by bacterial proteome changes, suggesting involvement of bacterial proteins in host satiety. Indeed, intestinal infusions of E. coli stationary phase proteins increased plasma PYY and their intraperitoneal injections suppressed acutely food intake and activated c-Fos in hypothalamic POMC neurons, while their repeated administrations reduced meal size. ClpB, a bacterial protein mimetic of α-MSH, was upregulated in the E. coli stationary phase, was detected in plasma proportional to ClpB DNA in feces, and stimulated firing rate of hypothalamic POMC neurons. Thus, these data show that bacterial proteins produced after nutrient-induced E. coli growth may signal meal termination. Furthermore, continuous exposure to E. coli proteins may influence long-term meal pattern.

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