Bacterial ClpB heat-shock protein, an antigen-mimetic of the anorexigenic peptide α-MSH, at the origin of eating disorders
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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.
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Chronic intragastric delivery of ClpB-expressing E. coli in mice stimulated production of α-MSH-reactive antibodies and decreased food intake.
“chronic intragastric delivery of ClpB-expressing E. coli in mice stimulated the production of α-MSH-reactive antibodies and decreased food intake (Breton et al., 2016b;Tennoune et al., 2014).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Tennoune et al., 2014
Autoantibody-induced interference with the central melanocortin system is one of the key microbiota-gut-brain mechanisms contributing to dysregulated appetite control in eating disorders.
“Finally, data on the bacterial protein C1pB (produced by both commensal and pathogenic microorganisms) as a mimetic of α-MSH and its effects on activating host satiety pathways in rodents [47], as well as the elevated plasma concentration of anti-C1pB IgG that is cross-reactive with α-MSH in patients with eating disorders [48], accord with the notion that autoantibody-induced interference with the”
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Self-citation
- Authors
- Tennoune, N., Chan, P., Breton, J., Legrand, R., Chabane, Y. N., Akkermann, K., Järv, A., Ouelaa, W., Takagi, K., Ghouzali, I., Francois, M., Lucas, N., Bole-Feysot, C., Pestel-Caron, M., do Rego, J.-C., Vaudry, D., Harro, J., Dé, E., Déchelotte, P., & Fetissov, S. O.
- Affiliations
- Inserm (FR)
- Institute for Research and Innovation in Biomedicine (FR)
- Centre National de la Recherche Scientifique (FR)
- Tartu University Hospital (EE)
- Corresponding author
- Fetissov, S O
- ORCID
- Venue
- Translational Psychiatry
- Published
- 2014-10-07
- Volume
- 4
- Issue
- 10
- Pages
- e458-e458
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC4350527
- OpenAlex
- W2151670857
- Cited by
- 218
- References
- 48
- Citations by year
- 2026: 14 · 2025: 17 · 2024: 27 · 2023: 21 · 2022: 21 · 2021: 22 · 2020: 15 · 2019: 16 · 2018: 13 · 2017: 15 · 2016: 17 · 2015: 18 · 2014: 2
- FWCI
- 20.91
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Translational Psychiatry (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- European Commission
- Région Normandie
- Langley Research Center
- Japan Society for the Promotion of Science (25670355)
- Interreg
- Topics
- Social Sciences › Psychology › Clinical Psychology › Eating Disorders and Behaviors
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Psychiatry and Mental health › Child Nutrition and Feeding Issues
- Keywords
- alpha-melanocyte-stimulating hormone, autoantibodies, antigen mimicry, eating disorders, anorexia nervosa, bulimia nervosa, binge eating disorder, Escherichia coli, gut commensal bacteria, anxiety, dietary intake, gut microbiota, autoimmunity
- MeSH terms
- Adolescent, Adult, alpha-MSH, Animals, Feeding and Eating Disorders, Autoantibodies, Disease Models, Animal, Electrophoresis, Polyacrylamide Gel, Escherichia coli, Female, Heat-Shock Proteins, Humans, Male, Mice, Inbred C57BL, Immunoblotting, Escherichia coli Proteins, Endopeptidase Clp, Mice, Young Adult
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