An Epigenomic Meta-Analysis of Differentially Methylated Sites in Pre- and Post-Metabolic/Bariatric Surgery Adult Female Patients.

Background/objectives: Metabolic/bariatric surgery is currently the most successful treatment for patients with obesity; however, a fifth of patients undergoing surgery may not lose enough weight to be considered successful. Recent studies have shown that bariatric/metabolic surgery alters the epigenome and may explain postoperative improvements in metabolic health. The primary objective is to consolidate published differentially methylated CpG sites in pre- and post-metabolic/bariatric surgery female patients and associate them with the respective genes and pathways.

Methods: This systematic review adhered to the PRISMA-P guidelines and was registered with the PROSPERO (CRD42023421852). Following an initial screening of 541 studies using COVIDENCE, six studies were selected, comprising three epigenome-wide association studies (EWAS) and three candidate gene methylation studies. The published studies collected DNA samples from female patients with obesity before and after surgery (3 months, 6 months, 9-31 months, and 2 years). KEGG pathway analysis was performed on genes where the extracted CpG sites were located.

Results: The meta-analysis showed that 11,456 CpG sites are differentially methylated after a successful weight loss surgery, with 109 sites mapped to genes involved in key metabolic pathways, including FoxO, mTOR, insulin, cAMP, adipocytokine, Toll-like receptor, and PI3K-Akt.

Conclusion: The highlighted differentially methylated CpG sites can be further used to predict the molecular signature associated with successful metabolic/bariatric surgery.