The molecular mechanisms at the origin of eating disorders (EDs), including anorexia nervosa (AN), bulimia and binge-eating disorder (BED), are currently unknown. Previous data indicated that immunoglobulins (Igs) or autoantibodies (auto-Abs) reactive with α-melanocyte-stimulating hormone (α-MSH) are involved in regulation of feeding and emotion; however, the origin of such auto-Abs is unknown. Here, using proteomics, we identified ClpB heat-shock disaggregation chaperone protein of commensal gut bacteria Escherichia coli as a conformational antigen mimetic of α-MSH. We show that ClpB-immunized mice produce anti-ClpB IgG crossreactive with α-MSH, influencing food intake, body weight, anxiety and melanocortin receptor 4 signaling. Furthermore, chronic intragastric delivery of E. coli in mice decreased food intake and stimulated formation of ClpB- and α-MSH-reactive antibodies, while ClpB-deficient E. coli did not affect food intake or antibody levels. Finally, we show that plasma levels of anti-ClpB IgG crossreactive with α-MSH are increased in patients with AN, bulimia and BED, and that the ED Inventory-2 scores in ED patients correlate with anti-ClpB IgG and IgM, which is similar to our previous findings for α-MSH auto-Abs. In conclusion, this work shows that the bacterial ClpB protein, which is present in several commensal and pathogenic microorganisms, can be responsible for the production of auto-Abs crossreactive with α-MSH, associated with altered feeding and emotion in humans with ED. Our data suggest that ClpB-expressing gut microorganisms might be involved in the etiology of EDs.

Obesity, a worldwide health concern with a constantly rising prevalence, is a multifactorial chronic disease associated with a wide range of physiological disruptions, including energy imbalance, central appetite and food reward dysregulation, and hormonal alterations and gut dysbiosis. The gut microbiome is a well-recognized factor in the pathophysiology of obesity, and its influence on host physiology has been extensively investigated over the last decade. This review highlights the mechanisms by which gut dysbiosis can contribute to the pathophysiology of obesity. In particular, we discuss gut microbiota’s contribution to host energy homeostatic changes, low-grade inflammation, and regulation of fat deposition and bile acid metabolism via bacterial metabolites, such as short-chain fatty acids, and bacterial components, such as lipopolysaccharides, among others. Finally, therapeutic strategies based on next-generation probiotics aiming to re-shape the intestinal microbiota and reverse metabolic alterations associated with obesity are described.