ABSTRACT
Altered signaling between gut bacteria and their host has recently been implicated in the pathophysiology of eating disorders, whereas the enterobacterial caseinolytic protease B (ClpB) may play a key role as an antigen mimetic of α-melanocyte-stimulating hormone, an anorexigenic neuropeptide. Here, we studied whether ClpB production by gut bacteria can be modified by chronic food restriction and female sex, two major risk factors for the development of eating disorders. We found that food restriction increased ClpB DNA in feces and ClpB protein in plasma in both male and female rats, whereas females displayed elevated basal ClpB protein levels in the lower gut and plasma as well as increased ClpB-reactive immunoglobulins (Ig)M and IgG. In contrast, direct application of estradiol in E. coli cultures decreased ClpB concentrations in bacteria, while testosterone had no effect. Thus, these data support a mechanistic link between host-dependent risk factors of eating disorders and the enterobacterial ClpB protein production.
ABSTRACT
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.