Host Starvation and Female Sex Influence Enterobacterial ClpB Production: A Possible Link to the Etiology of Eating Disorders.

Jonathan Breton,Nathalie Connil,Pierre Déchelotte,Linda Yaker,Marc Feuilloley,Sergueï O Fetissov,Camille Leclerc,Justine Jacquemot

doi:10.3390/microorganisms8040530

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.

Highlights

Complex interactions between the host genome and bacterial metagenome may contribute to the risk factors to develop anorexia nervosa (AN) and bulimia nervosa (BN), two main forms of eating disorders (EDs) in humans [1]
In this light, altered signaling between gut bacteria and their host has recently been implicated in the pathophysiology of EDs, whereas the enterobacterial caseinolytic protease B (ClpB) protein may play a key role as an antigen mimetic of α-melanocyte-stimulating hormone (α-MSH), an anorexigenic neuropeptide [5,6]
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Summary

Introduction

Complex interactions between the host genome and bacterial metagenome may contribute to the risk factors to develop anorexia nervosa (AN) and bulimia nervosa (BN), two main forms of eating disorders (EDs) in humans [1]. A genetic predisposition for autoimmunity and its significant association with ED strongly support an autoimmune component in the mechanism of both AN and BN [2,3,4]. In this light, altered signaling between gut bacteria and their host has recently been implicated in the pathophysiology of EDs, whereas the enterobacterial caseinolytic protease B (ClpB) protein may play a key role as an antigen mimetic of α-melanocyte-stimulating hormone (α-MSH), an anorexigenic neuropeptide [5,6]. The mechanism of action of α-MSH-reactive IgG may include activation of MC4R by the immune complexes with α-MSH, which deregulates feeding behavior and emotions [9]

Methods

Results

Discussion

Conclusion