Coordinated changes of gut microbiome and lipidome differentiates nonalcoholic steatohepatitis (NASH) from isolated steatosis

作者：Minyi Qian, Hai Hu, Ying Yao, Danyang Zhao, Shilei Wang, Chuyue Pan, Xubin Duan, Yingsheng Gao, Jun Liu, Yufei Zhang, Song Yang, Lian‐Wen Qi, Lirui Wang · 发表于：Liver International · 年份：2019 · DOI：10.1111/liv.14316 · 被引用次数：54 · 研究领域：Liver Disease Diagnosis and Treatment、Gut microbiota and health、Diet and metabolism studies

BACKGROUND & AIMS: Nonalcoholic fatty liver disease encompasses isolated steatosis or nonalcoholic fatty liver and nonalcoholic steatohepatitis (NASH). NASH develops from isolated steatosis with obscure driving forces. We aim to identify key factors promoting this transition. METHODS: Following 21-week of high-fat diet feeding, obese mice were classified into two groups termed as isolated steatosis and NASH based on hematoxylin-eosin staining of liver histology. The integrated multi-omics analysis of lipidome, transcriptome and gut microbiome were performed in mice with isolated steatosis and NASH, and confirmed in human samples. RESULTS: Livers in mice with NASH lost most lipids, and the transcriptional landscape was also changed dramatically in mice with NASH in relative to mice with isolated steatosis. Plasma lipidome analysis demonstrated a very clear difference between these two groups of mice, which was partially recapitulated in serum of patients with isolated steatosis and NASH. The microbiota composition revealed that Bacteroides genus and Bacteroides uniformis species decreased while Mucispirillum genus and Mucispirillum schaedleri species increased largely in mice with NASH. More importantly, we found that Bacteroides uniformis correlated positively with triglycerides (TGs) and negatively with free fatty acids (FFAs) and PE(18:1/20:4), while Mucispirillum schaedleri correlated positively with FFAs, LysoPC(20:3), LysoPC(20:4) and DG(16:1/18:2). Mechanically, adminis...