代谢功能障碍相关的脂肪肝病(MASLD),以前称为非酒精性脂肪肝病(NAFLD),是由肝脏代谢改变引起的。作为一种关键的代谢功能调节剂,烟酰胺腺嘌呤二核苷酸(NAD)目前已被证实可有效治疗饮食诱导的 MASLD 小鼠模型。此外,据报道,肠道微生物群有可能通过膳食 NAD 前体与哺乳动物一起代谢来预防 MASLD。然而,其根本机制仍不清楚。在这篇综述中,我们假设 NAD 增强线粒体活性可能会重塑特定的微生物群特征,并改善粪便微生物群移植所证明的 MASLD 进展。在此,本综述特别关注微生物群-肠-肝轴以及 NAD 代谢对 MASLD 进展的机制。值得注意的是,我们发现某些 MASLD 患者肠道微生物组特征中与 NAD 相关的显着变化。通过最近的研究,我们还推断,它不仅可以通过促进碳代谢来调节NAD池的水平,而且在调节支链氨基酸(BCAA)相关的脂肪酸代谢途径中发挥着重要作用。总而言之,我们的结果支持这样的观点,即肠道微生物群有助于 MASLD 发展中的膳食 NAD 前体代谢,并且膳食 NAD 前体与某些肠道微生物群一起可能是 MASLD 管理中的预防或治疗策略。
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NAD metabolic therapy in metabolic dysfunction-associated steatotic liver disease: Possible roles of gut microbiota
Metabolic dysfunction–associated steatotic liver disease (MASLD), formerly named non-alcoholic fatty liver disease (NAFLD), is induced by alterations of hepatic metabolism. As a critical metabolites function regulator, nicotinamide adenine dinucleotide (NAD) nowadays has been validated to be effective in the treatment of diet-induced murine model of MASLD. Additionally, gut microbiota has been reported to have the potential to prevent MASLD by dietary NAD precursors metabolizing together with mammals. However, the underlying mechanism remains unclear. In this review, we hypothesized that NAD enhancing mitochondrial activity might reshape a specific microbiota signature, and improve MASLD progression demonstrated by fecal microbiota transplantation. Here, this review especially focused on the mechanism of Microbiota-Gut-Liver Axis together with NAD metabolism for the MASLD progress. Notably, we found significant changes in associated with NAD in a gut microbiome signature of certain MASLD patients. With the recent researches, we also inferred that can not only regulate the level of NAD pool by boosting the carbon metabolism, but also play a vital part in regulating the branched-chain amino acid (BCAA)-related fatty acid metabolism pathway. Altogether, our results support the notion that the gut microbiota contribute to the dietary NAD precursors metabolism in MASLD development and the dietary NAD precursors together with certain gut microbiota may be a preventive or therapeutic strategy in MASLD management.