改良型柑橘果胶通过阿利斯特氏歧杆菌-烟酸-苏黎世蛋白激酶1轴，调控肝脏氧化还原平衡，缓解代谢功能障碍相关脂肪肝病变。

Abstract

Background Modified citrus pectin (MCP) is a bioactive functional component with potential metabolic benefits, but its therapeutic mechanisms in metabolic dysfunction-associated steatotic liver disease (MASLD) remain unclear. Purpose To determine whether MCP alleviates MASLD through gut microbiota remodelling and to identify the key microbial and metabolic mediators involved. Study design MASLD mouse models, multi-omics analyses, fecal microbiota transplantation (FMT), bacterial supplementation, and pharmacological inhibition were integrated to establish microbiota–metabolite–host causality. Methods MCP efficacy was evaluated by assessing hepatic steatosis, inflammation, oxidative stress, and lipid metabolism. Metagenomics and metabolomics were used to identify MCP-responsive microbes and metabolites. FMT, administration of live or heat-killed Alistipes dispar , validation in db/db mice, and SIRT1 knockdown and inhibition with EX-527 were performed to verify causality and mechanism. Results MCP markedly reduced hepatic lipid accumulation, inflammation, and oxidative stress. Metagenomics identified enrichment of A. dispar as a key microbial signature associated with MCP efficacy. Live, but not heat-killed, A. dispar reproduced the protective effects of MCP and improved metabolic abnormalities in db/db mice. Mechanistically, MCP promoted A. dispar proliferation and increased nicotinamide levels, activating hepatic nicotinamide salvage and the SIRT1/PGC-1α/PPARα/CPT1A axis to enhance fatty acid oxidation. This response also suppressed COX-2/HMGB1-mediated inflammation and activated Nrf2/HO-1 antioxidant defence. EX-527 abolished the beneficial effects of MCP and A. dispar . Conclusion MCP alleviates MASLD through an A. dispar –nicotinamide–SIRT1 axis that restores metabolic, inflammatory, and redox homeostasis. Download: Download high-res image (297KB) Download: Download full-size image