上海交通大学医学院贾伟团队取得一项新突破。他们发现了靶向微生物产生的乙醛以预防代谢功能障碍相关的脂肪变性肝病的进展。相关论文于2026年3月2日发表于国际顶尖学术期刊《细胞—代谢》杂志上。

研究小组证明，过量的饮食糖摄入，特别是果糖，通过微生物介导的内源性乙醛生产的扩增，加剧了肝脏疾病的进展。对来自英国生物银行的21万多名参与者的分析显示，糖消耗与肝脏相关死亡率之间存在剂量依赖性相关性，同时在MASH患者中伴随着有利于乙醛/乙醇发酵途径的微生物转变。从机制上说，肠源性乙醛通过上调基质金属蛋白酶-7（MMP7）激活肝星状细胞，促进纤维形成。为了减轻这种情况，研究团队设计了一种具有增强乙醛降解能力的益生菌Liilactobacillthem salivarithem HAM，它有效地阻止了饮食性肝病临床前模型中的纤维化进展。这些发现强调了以微生物群为目标的醛代谢调节是阻断从MASLD到MASH转变的有希望的治疗途径。

据介绍，从代谢功能障碍相关的脂肪性肝病（MASLD）到脂肪性肝炎（MASH）的进展伴随着快速的，通常是不可逆的肝损伤，强调了迫切需要创新的治疗策略。

附：英文原文

Title: Targeting microbiota-generated acetaldehyde to prevent progression of metabolic dysfunction-associated steatotic liver disease

Author: Yajun Tang, Junliang Kuang, Xixi Xia, Changliang Yao, Zile Zhou, Jiajian Liu, Zhenxing Ren, Keke Ding, Mengci Li, Yang Li, Fuxin Jiao, Dan Zheng, Tianlu Chen, Aihua Zhao, Xinjian Wan, Guang Ji, Shan Zhang, Xiaojiao Zheng, Wei Jia

Issue&Volume: 2026-03-02

Abstract: The progression from metabolic dysfunction-associated steatotic liver disease (MASLD) to steatohepatitis (MASH) entails rapid, often irreversible hepatic injury, underscoring the urgent need for innovative therapeutic strategies. Here, we demonstrate that excessive dietary sugar intake, particularly fructose, exacerbates liver disease progression through microbiota-mediated amplification of endogenous acetaldehyde production. Analysis of over 210,000 participants from the UK Biobank revealed a dose-dependent correlation between sugar consumption and liver-related mortality, accompanied by a microbial shift favoring acetaldehyde/ethanol fermentation pathways in MASH patients. Mechanistically, gut-derived acetaldehyde activates hepatic stellate cells via upregulation of matrix metalloproteinase-7 (MMP7), driving fibrogenesis. To mitigate this, we engineered Ligilactobacillus salivarius HAM, a probiotic strain with enhanced acetaldehyde-degrading capacity, which effectively halted fibrosis progression in preclinical models of diet-induced liver disease. These findings highlight microbiota-targeted modulation of aldehyde metabolism as a promising therapeutic avenue to intercept the transition from MASLD to MASH.

DOI: 10.1016/j.cmet.2026.01.021

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(26)00043-4