| Title: | Targeting microbiota-generated acetaldehyde to prevent progression of metabolic dysfunction-associated steatotic liver disease |
| Journal: | Cell Metabolism |
| Published: | 2 Mar 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41775257/ |
| DOI: | https://doi.org/10.1016/j.cmet.2026.01.021 |
Publication 17550
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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.</p>
19 Authors
- 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
Enabling scientific discoveries that improve human health