Editors' ChoiceHost-Microbe Interactions

Bacteria give that full feeling

Sci. Signal.  23 Feb 2016:
Vol. 9, Issue 416, pp. ec37
DOI: 10.1126/scisignal.aaf5075

Microbes in the gut play important roles in the regulation of behavior of their host. Breton et al. examined if the bacterial proteome from exponentially growing bacteria or bacteria in the stationary phase influenced food intake in rats using Escherichia coli K12 as a model of a commensal bacteria. In culture, E. coli exhibited exponential growth following the addition of nutrient-rich medium that lasted 20 minutes and was followed by a stationary phase. Comparison of the proteome 10 minutes after nutrient supply (exponentially growing) with that 2 hours into the stationary phase showed that ~20 membrane and ~20 cytoplasmic proteins differed. The abundance of caseolytic protease B (ClpB), which is antigenically similar to α-melanocyte–stimulating hormone (α-MSH, a satiety hormone), was higher in samples from stationary phase bacteria than those from exponentially growing bacteria. Colonic infusion of nutrient-rich medium or water into rats also induced exponential bacterial growth lasting 20 minutes. Colonic infusion of proteins from exponentially growing bacteria stimulated an increase in plasma glucagon-like peptide-1 (GLP-1, a satiety hormone) 20 minutes after infusion. In contrast, infusion of proteins from stationary phase bacteria increased the amount of ClpB in the colonic mucosa, but not the circulation, and increased the amount of the satiety hormone peptide YY (PYY) in the circulation. Thus, proteins from both exponentially growing and stationary phase bacteria can stimulate an increase in circulating satiety hormones. Intraperitoneal injection of proteins from stationary phase bacteria reduced food intake for 2 hours compared with control rats, whereas injection of proteins from exponentially growing bacteria did not change food intake. Immunohistochemical analysis of the brain regions responsible for controlling food intake showed that the injection of proteins from stationary phase bacteria activated anorexigenic neurons, both in regions of the brain accessible to the circulation and those receiving synaptic input from the accessible regions. Although twice daily injections of bacterial proteins from either of the two growth phases did not change total food intake, the time of eating differed. Mice injected twice daily with proteins from exponentially growing bacteria exhibited increased food intake during the inactive period and decreased food intake during the active period, whereas mice receiving proteins from stationary phase bacteria had reduced food intake during the active period without any change during the inactive period. Application of ClpB to brain slice preparations from mice transgenically expressing a fluorescent reporter in neurons involved in feeding behavior increased the action potentials of the labeled neurons, confirming that bacterial proteins could directly affect the activity of the feeding circuit in the brain. Thus, regular meals not only feed the host but also feed the gut microbes, and these bacterial companions help their host feel full.

J. Breton, N. Tennoune, N. Lucas, M. Francois, R. Legrand, J. Jacquemot, A. Goichon, C. Guérin, J. Peltier, M. Pestel-Caron, P. Chan, D. Vaudry, J.-C. do Rego, F. Liénard, L. Pénicaud, X. Fioramonti, I. S. Ebenezer, T. Hökfelt, P. Déchelotte, S. O. Fetissov, Gut commensal E. coli proteins activate host satiety pathways following nutrient-induced bacterial growth. Cell Metab. 23, 324–334 (2016). [PubMed]