A new concept (Figure 1) explaining molecular mechanisms of the communication in the gut microbiota - brain axis has postulated a role of bacterial mimetic proteins of neuropeptides (1). It was triggered by the key finding in patients with eating disorders of autoantibodies directed against α-MSH, an anorexigenic neuropeptide (2) and later complemented by discovery of the Escherichia coli protein ClpB responsible for the production of such antibodies (3). Moreover, a direct anorexigenic effect of ClpB was discovered (4), resulting in the development of the first probiotic to control appetite and body weight by the French start-up TargEDys (www.targedys.com). Our recent studies have extended this concept by discovery in Lactobacilli of a bacterial mimetic protein of oxytocin, a neuropeptide involved in regulation of stress and social behavior resulting in patent application and introduction by TargEDys of the new anti-stress probiotic preparation (5). Currently, we validate this protein as a putative molecular target in ASD in the frame of the H2020 European consortium GEMMA.

Figure 1. Postulated direct (1) and indirect (2) effects of ClpB in signaling satiety and regulation of body weight. As such, ClpB protein, having an α-MSH like epitope (depicted in red) may bind directly to MC4R or stimulate α-MSH cross-reactive IgG which, in turn, modulate α-MSH binding and activation of MC4R leading to stimulation of satiety. Figure modified from (1).

Moreover, a pathophysiological model of eating disorders has been proposed in which α-MSH-cross-reactive autoantibodies with altered capacity to bind α-MSH may play a key pathogenic role (6). Currently, we validate this model using the activity-based anorexia model in mice as well as clinical studies in the frame of the ERAnet consortium MIGBAN. Numerous experimental evidence has been obtained suggesting a role of neuropeptide-reactive IgG as a natural neuropeptide-carrier molecule which modulates the neuropeptide activation of its receptor (7). Our recent studies of oxytocin- and α-MSH- binding IgG further support such role of plasmatic IgG as a general phenomenon in peptidergic signaling.