Changes in Microbiota and Bacterial Protein Caseinolytic Peptidase B During Food Restriction in Mice: Relevance for the Onset and Perpetuation of Anorexia Nervosa.

Manon Dominique,Fatima Leon,Marie Galmiche,Charlène Guérin,Jean-Luc Do Rego,Nicolas Lucas,Saïda Azhar,Romain Legrand,Séverine Nobis,Grégory Lambert,Pierre Déchelotte,Camille Deroissart

doi:10.3390/nu11102514

Abstract

Microbiota contributes to the regulation of eating behavior and might be implicated in the pathophysiology of anorexia nervosa. ClpB (Caseinolytic peptidase B) protein produced mainly by the Enterobacteriaceae family has been identified as a conformational mimetic of α-MSH, which could result in similar anorexigenic effects. The aim of this study was to highlight the role of the microbiome and the ClpB protein in deregulation and self-maintenance of anorexia pathology. Male C57Bl/6 mice were undergone to the ABA (Activity-Based Anorexia) protocol: after 5 days of acclimatization, both ABA and LFA (Limited Food Access) mice had progressively limited access to food until D17. At the end of protocol, the plasma ClpB concentration and Enterobacteriaceae DNA in colonic content were measured. As expected, dietary restriction induced lost weight in LFA and ABA mice. At D10, colonic permeability and plasma concentration of the ClpB protein were significantly increased in LFA and ABA mice vs. controls. At D17, plasma concentration of ClpB was increased in LFA and ABA mice and, it was correlated with proportion of Enterobacteriaceae in the faeces. These abnormally high ClpB concentrations and all associated factors, and therefore might contribute to the initiation and/or perpetuation of anorexia nervosa by interfering with satiety signaling.

Highlights

Eating Disorders (ED) are public health problems that have continued to worsen in recent years with a prevalence of 3.5% from 2000–2006 to 7.8% in 2013–2018 [1]
The Activity-Based Anorexia (ABA) and LFA mice lost significant weight compared to the control (** p < 0.01, D7, D8)
We highlighted that an increase of ClpB plasma concentration correlated with the

Summary

Introduction

Eating Disorders (ED) are public health problems that have continued to worsen in recent years with a prevalence of 3.5% from 2000–2006 to 7.8% in 2013–2018 [1]. Among these disorders, anorexia nervosa (AN) is characterized by a difficulty in maintaining a minimum weight and an obsession with weight and body shape [2], the pathophysiology of which is multifactorial and remains partially debated [3]. Are modulated at least in part by several gut-microbiota derived signals, among which bacterial products (e.g., peptides, neurotransmitters) have been shown to influence peripheral and central mechanisms of satiety, reward [11,12] and anxiety [13]. Microbiota composition is implicated in the regulation of body composition: dysbiosis has been reported both in obese individuals [14] and in patients with

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