On the origin of eating disorders: altered signaling between gut microbiota, adaptive immunity and the brain melanocortin system regulating feeding behavior

Research in the field of gut microbiota – brain axis may contribute to clarifying the origin of anorexia nervosa and bulimia, the two principal forms of eating disorders (ED). The initial key findings in ED patients of plasma immunoglobulins (Ig) that react with α-melanocyte-stimulating hormone (α-MSH), a neuropeptide in the brain signaling satiety, have initiated further studies leading to the discovery of the origin of such autoantibodies and to the understanding their possible functional role. An anorexigenic bacterial protein Escherichia coli caseinolytic protease B was recently found to be responsible for the production of α-MSH-cross-reactive autoantibodies and this protein was also detected in human plasma. Another recent study revealed enhanced activation of appetite-regulating the melanocortin type 4 receptor by immune complexes withα-MSH. Taken together, these data serve to build a pathophysiological model of ED presented in this article.