title: Bacterial ClpB heat-shock protein, an antigen-mimetic of the anorexigenic peptide α-MSH, at the origin of eating disorders.
abstract: The molecular mechanisms at the origin of eating disorders (EDs), including anorexia nervosa (AN), bulimia and binge-eating disorder (BED), are currently unknown. Previous data indicated that immunoglobulins (Igs) or autoantibodies (auto-Abs) reactive with α-melanocyte-stimulating hormone (α-MSH) are involved in regulation of feeding and emotion; however, the origin of such auto-Abs is unknown. Here, using proteomics, we identified ClpB heat-shock disaggregation chaperone protein of commensal gut bacteria Escherichia coli as a conformational antigen mimetic of α-MSH. We show that ClpB-immunized mice produce anti-ClpB IgG crossreactive with α-MSH, influencing food intake, body weight, anxiety and melanocortin receptor 4 signaling. Furthermore, chronic intragastric delivery of E. coli in mice decreased food intake and stimulated formation of ClpB- and α-MSH-reactive antibodies, while ClpB-deficient E. coli did not affect food intake or antibody levels. Finally, we show that plasma levels of anti-ClpB IgG crossreactive with α-MSH are increased in patients with AN, bulimia and BED, and that the ED Inventory-2 scores in ED patients correlate with anti-ClpB IgG and IgM, which is similar to our previous findings for α-MSH auto-Abs. In conclusion, this work shows that the bacterial ClpB protein, which is present in several commensal and pathogenic microorganisms, can be responsible for the production of auto-Abs crossreactive with α-MSH, associated with altered feeding and emotion in humans with ED. Our data suggest that ClpB-expressing gut microorganisms might be involved in the etiology of EDs.
authors.affiliation: 1] Inserm UMR1073, Nutrition, Gut and Brain Laboratory, Rouen, France [2] Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen, France.
authors.forename: N
authors.initials: N
authors.lastname: Tennoune
authors.affiliation: 1] Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen, France [2] PISSARO Proteomic Platform, Mont-Saint-Aignan, France.
authors.forename: P
authors.initials: P
authors.lastname: Chan
authors.affiliation: 1] Inserm UMR1073, Nutrition, Gut and Brain Laboratory, Rouen, France [2] Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen, France.
authors.forename: J
authors.initials: J
authors.lastname: Breton
authors.affiliation: 1] Inserm UMR1073, Nutrition, Gut and Brain Laboratory, Rouen, France [2] Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen, France.
authors.forename: R
authors.initials: R
authors.lastname: Legrand
authors.affiliation: 1] Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen, France [2] Polymères, Biopolymères, Surfaces, UMR 6270 CNRS, Mont-Saint-Aignan, France.
authors.forename: Y N
authors.initials: YN
authors.lastname: Chabane
authors.affiliation: Department of Psychology, Estonian Centre of Behavioural and Health Sciences, Tartu, Estonia.
authors.forename: K
authors.initials: K
authors.lastname: Akkermann
authors.affiliation: Tartu University Clinics, Psychiatric Hospital, University of Tartu, Tartu, Estonia.
authors.forename: A
authors.initials: A
authors.lastname: Järv
authors.affiliation: 1] Inserm UMR1073, Nutrition, Gut and Brain Laboratory, Rouen, France [2] Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen, France.
authors.forename: W
authors.initials: W
authors.lastname: Ouelaa
authors.affiliation: 1] Inserm UMR1073, Nutrition, Gut and Brain Laboratory, Rouen, France [2] Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen, France.
authors.forename: K
authors.initials: K
authors.lastname: Takagi
authors.affiliation: 1] Inserm UMR1073, Nutrition, Gut and Brain Laboratory, Rouen, France [2] Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen, France.
authors.forename: I
authors.initials: I
authors.lastname: Ghouzali
authors.affiliation: 1] Inserm UMR1073, Nutrition, Gut and Brain Laboratory, Rouen, France [2] Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen, France.
authors.forename: M
authors.initials: M
authors.lastname: Francois
authors.affiliation: 1] Inserm UMR1073, Nutrition, Gut and Brain Laboratory, Rouen, France [2] Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen, France.
authors.forename: N
authors.initials: N
authors.lastname: Lucas
authors.affiliation: 1] Inserm UMR1073, Nutrition, Gut and Brain Laboratory, Rouen, France [2] Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen, France.
authors.forename: C
authors.initials: C
authors.lastname: Bole-Feysot
authors.affiliation: 1] Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen, France [2] Microbiology Laboratory GRAM, EA2656, Rouen, France [3] Rouen University Hospital, CHU Charles Nicolle, Rouen, France.
authors.forename: M
authors.initials: M
authors.lastname: Pestel-Caron
authors.affiliation: 1] Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen, France [2] Animal Behavior Platform (SCAC), Rouen, France.
authors.forename: J-C
authors.initials: JC
authors.lastname: do Rego
authors.affiliation: 1] Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen, France [2] PISSARO Proteomic Platform, Mont-Saint-Aignan, France.
authors.forename: D
authors.initials: D
authors.lastname: Vaudry
authors.affiliation: Department of Psychology, Estonian Centre of Behavioural and Health Sciences, Tartu, Estonia.
authors.forename: J
authors.initials: J
authors.lastname: Harro
authors.affiliation: 1] Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen, France [2] Polymères, Biopolymères, Surfaces, UMR 6270 CNRS, Mont-Saint-Aignan, France.
authors.forename: E
authors.initials: E
authors.lastname: Dé
authors.affiliation: 1] Inserm UMR1073, Nutrition, Gut and Brain Laboratory, Rouen, France [2] Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen, France [3] Rouen University Hospital, CHU Charles Nicolle, Rouen, France.
authors.forename: P
authors.initials: P
authors.lastname: Déchelotte
authors.affiliation: 1] Inserm UMR1073, Nutrition, Gut and Brain Laboratory, Rouen, France [2] Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen, France.
authors.forename: S O
authors.initials: SO
authors.lastname: Fetissov
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D049071:Endopeptidase Clp; D004926:Escherichia coli / Q000276:immunology*; D029968:Escherichia coli Proteins / Q000276:immunology*; D001068:Feeding and Eating Disorders / Q000097:blood* / Q000276:immunology*; D005260:Female; D006360:Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D015151:Immunoblotting; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055815:Young Adult; D000521:alpha-MSH / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D029968:Escherichia coli Proteins; D006360:Heat-Shock Proteins; D000521:alpha-MSH; D049071:Endopeptidase Clp; C069775:ClpB protein, E coli