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Transl Psychiatry. 2014 Oct 7;4:e458. doi: 10.1038/tp.2014.98.

Bacterial ClpB heat-shock protein, an antigen-mimetic of the anorexigenic peptide α-MSH, at the origin of eating disorders.

Author information

1
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.
2
1] Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen, France [2] PISSARO Proteomic Platform, Mont-Saint-Aignan, France.
3
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.
4
Department of Psychology, Estonian Centre of Behavioural and Health Sciences, Tartu, Estonia.
5
Tartu University Clinics, Psychiatric Hospital, University of Tartu, Tartu, Estonia.
6
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.
7
1] Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen, France [2] Animal Behavior Platform (SCAC), Rouen, France.
8
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.

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.

PMID:
25290265
PMCID:
PMC4350527
DOI:
10.1038/tp.2014.98
[Indexed for MEDLINE]
Free PMC Article

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