Cell Metab. 23, 324–334 (2016)

The gut microbiota is important in the metabolism of nutrients consumed by the host organism. It is thought that these bacteria can also influence host feeding behavior through the regulation of neuronal pathways responsible for appetite control and satiety. Several potential mechanisms for controlling food uptake exist, but it has not been known if bacterial-derived proteins could influence appetite-controlling pathways. Breton et al. first determined that the growth dynamics of regularly fed Escherichia coli K12 cells are associated with the host prandial and postprandial phases in rats and then used a proteomics approach to identify differences between proteins secreted by the bacteria after ten minutes (exponential phase of growth, Exp) and two hours (stationary phase, Stat). They found 20 differentially expressed membrane proteins and 20 differentially expressed cytoplasmic proteins, most of which have been implicated in anabolic or catabolic processes. One specific E. coli protein, ClpB, known to cause release of the satietogenic hormones GLP-1 and PYY, was increased in the Stat growth phase. The authors next introduced the E. coli proteins secreted during Exp- and Stat-phase growth into rats by colonic infusion and found that the Exp proteins increased plasma GLP-1 levels, whereas the Stat proteins increased plasma PYY as well as ClpB in the colonic mucosa. These results, as well as a set of electrophysiology experiments, suggest that bacterial proteins produced during nutrient-induced bacterial growth may control appetite via stimulation of satiety hormones locally in the gut and, after they reach the systemic circulation, via activation of central anorexigenic circuitries.