Long-Term Dynamics of Serum α-MSH and α-MSH-Binding Immunoglobulins with a Link to Gut Microbiota Composition in Patients with Anorexia Nervosa

Neuroendocrinology. 2024;114(10):907-920. doi: 10.1159/000539316. Epub 2024 Jun 8.

Abstract

Introduction: Immunoglobulins (Ig) reactive with α-melanocyte-stimulating hormone (α-MSH), an anorexigenic neuropeptide, are present in humans and were previously associated with eating disorders. In this longitudinal study involving patients with anorexia nervosa (AN), we determined whether α-MSH in serum is bound to IgG and analyzed long-term dynamics of both α-MSH peptide and α-MSH-reactive Ig in relation to changes in BMI and gut microbiota composition.

Methods: The study included 64 adolescents with a restrictive form of AN, whose serum samples were collected at hospital admission, discharge, and during a 1-year follow-up visit and 41 healthy controls, all females.

Results: We found that in both study groups, approximately 40% of serum α-MSH was reversibly bound to IgG and that levels of α-MSH-reactive IgG but not of α-MSH peptide in patients with AN were low at hospital admission but recovered 1 year later. Total IgG levels were also low at admission. Moreover, BMI-standard deviation score correlated positively with α-MSH IgG in both groups studied but negatively with α-MSH peptide only in controls. Significant correlations between the abundance of specific bacterial taxa in the gut microbiota and α-MSH peptide and IgG levels were found in both study groups, but they were more frequent in controls.

Conclusion: We conclude that IgG in the blood plays a role as an α-MSH-binding protein, whose characteristics are associated with BMI in both patients with AN and controls. Furthermore, the study suggests that low production of α-MSH-reactive IgG during the starvation phase in patients with AN may be related to altered gut microbiota composition.

Keywords: Autoantibodies; Eating disorders; Gut microbiota-brain axis; Regulatory peptides; α-Melanocyte-stimulating hormone.

MeSH terms

  • Adolescent
  • Anorexia Nervosa* / blood
  • Anorexia Nervosa* / microbiology
  • Body Mass Index
  • Female
  • Gastrointestinal Microbiome* / physiology
  • Humans
  • Immunoglobulin G* / blood
  • Longitudinal Studies
  • Young Adult
  • alpha-MSH* / blood

Substances

  • alpha-MSH
  • Immunoglobulin G

Grants and funding

This study was supported by the ERANET Neuron MiGBAN consortium (01EW1906A-01 EW1906B), “Microbiome Gut-Brain Axis in Anorexia Nervosa,” funded by the European Union (EU), the German Ministry for Education and Research (BMBF), and the French Agence Nationale de la Recherche (ANR). S.O.F. research was also supported by the PTM2 program, in Inserm, France.