Autoantibodies against appetite-regulating peptide hormones and neuropeptides: putative modulation by gut microflora.
OBJECTIVE
Peptide hormones synthesized in gastrointestinal and adipose tissues in addition to neuropeptides regulate appetite and body weight. Previously, autoantibodies directed against melanocortin peptides were found in patients with eating disorders; however, it remains unknown whether autoantibodies directed against other appetite-regulating peptides are present in human sera and whether their levels are influenced by gut-related antigens.


METHODS
Healthy women were studied for the presence of immunoglobulin (Ig) G and IgA autoantibodies directed against 14 key appetite-regulating peptides. The concept of molecular mimicry was applied to search in silico whether bacteria, viruses, or fungi contain proteins with amino acid sequences identical to appetite-regulating peptides. In addition, autoantibodies serum levels were studied in germ-free and specific pathogen-free rats.


RESULTS
We found these IgG and IgA autoantibodies directed against leptin, ghrelin, peptide YY, neuropeptide Y, and other appetite-regulating peptides are present in human sera at levels of 100-900 ng/mL. Numerous cases of sequence homology with these peptides were identified among commensal and pathogenic micro-organisms including Lactobacilli, bacteroides, Helicobacter pylori, Escherichia coli, and Candida species. Decreased levels of IgA autoantibodies directed against several appetite-regulating peptides and increased levels of antighrelin IgG were found in germ-free rats compared with specific pathogen-free rats.


CONCLUSIONS
Healthy humans and rats display autoantibodies directed against appetite-regulating peptide hormones and neuropeptides, suggesting that these autoantibodies may have physiologic implications in hunger and satiety pathways. Gut-related antigens including the intestinal microflora may influence production of theses autoantibodies, suggesting a new link between the gut and appetite control.
Fetissov
Sergueï O
SO
Digestive System and Nutrition Laboratory (ADEN EA3234), Institute of Biomedical Research, Rouen University and Hospital, IFRMP23, Rouen, France. Serguei.Fetissov@univ-rouen.fr
Hamze Sinno
Maria
M
Coëffier
Moïse
M
Bole-Feysot
Christine
C
Ducrotté
Philippe
P
Hökfelt
Tomas
T
Déchelotte
Pierre
P
D000328:Adult; D000818:Animals; D001069:Appetite Regulation / Q000502:physiology*; D001323:Autoantibodies / Q000032:analysis / Q000097:blood*; D001835:Body Weight / Q000502:physiology; D004064:Digestive System / Q000382:microbiology*; D005260:Female; D054439:Ghrelin / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D009479:Neuropeptides / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms
D001323:Autoantibodies; D054439:Ghrelin; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D009479:Neuropeptides