Melatonin alleviates necrotizing enterocolitis by reducing bile acid levels through the SIRT1/FXR signalling axis

• DOI: 10.1016/j.intimp.2023.111360
• Publication Date: 2024-01-04T10:07:55Z
• Authors: Jiahao Lai; Fei Li; Hongfu Li; Rong Huang; Fei Ma; Xia Gu; Yao Cai; Dabin Huang; Sitao Li; Shangjie Xiao; Hu Hao
• Keywords: Farnesoid X receptor; Sirtuin 1; Necrotizing Enterocolitis

Bile acids (BAs) have increasingly been implicated in the onset and progression of necrotizing enterocolitis (NEC); multiple findings demonstrated their ability to induce damage intestinal epithelium, thereby exacerbating disease severity. Although we previously showed that melatonin was able treat NEC by correcting Treg/Th17 imbalance, modulatory effect on BAs remains unclear. In this study, conducted transcriptome analysis tissues from patients with validated these findings. Subsequently, treated mice alone or combination an agonist/inhibitor Sirtuin 1 (SIRT1) assess faecal serum BA levels, expression levels transporters regulators, extent injury. Our results indicated dysregulation metabolism abnormal NEC, which were also observed our mouse model. Furthermore, exogenous found aggravate severity mice. Notably, effectively restored aberrant transporters, such as apical membrane sodium-dependent bile acid (ASBT), ileal acid-binding protein (IBABP), organic solute transporter-alpha (OST-α), upregulating SIRT1 while reducing farnesoid X receptor (FXR) acetylation, consequently leading decreased mitigated Thus, propose a potential mechanism through reduces via SIRT1/FXR signalling axis Collectively, highlight holds promise for represents promising therapeutic strategy treating NEC.