Enterobacterial caseinolytic protease B (ClpB) and ClpB antibodies in adolescents with anorexia nervosa

Caseinolytic protease B (ClpB) produced by the gut enterobacteria displays anorexigenic effects possibly due to its molecular mimicry with α-melanocyte-stimulating hormone (α-MSH), an anorexigenic neuropeptide. ClpB is known to induce α-MSH cross-reactive antibodies previously associated with eating disorders. In the present study we analyzed whether long-term changes of serum ClpB, anti-ClpB antibodies and fecal clpB gene content can be associated with disease progression in anorexia nervosa (AN). For this purpose, female adolescents diagnosed with the restrictive type of AN according to DSM-5 were studied at hospital admission, discharge, and at a 1-year follow up visit, while age-matched healthy female participants served as a control group. We found that ClpB protein was detected at variable levels in sera of all study participants without significant group differences. However, anti-ClpB IgG were low in adolescents with AN at the acute phase of disease and were characterized by increased affinity. Long-term individual dynamics of serum ClpB revealed that its increase after hospital discharge was associated with disease relapse. In healthy adolescents, serum ClpB correlated negatively with BMI-SDS. Fecal clpB DNA levels were low in patients at hospital admission and discharge correlating positively with the abundance of Enterobacteriaceae in gut microbiota. Thus, in healthy adolescents enterobacterial ClpB appears as a physiological microbiota-derived factor associated with lower body weight within the normal range. Low levels of anti-ClpB IgG in adolescents with AN may cause insufficient immune control of ClpB, possibly promoting ClpB anorexigenic effects which can be relevant to the pathophysiology of AN.