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Coordinated changes of gut microbiome and lipidome differentiates nonalcoholic steatohepatitis (NASH) from isolated steatosis
Author(s) -
Qian Minyi,
Hu Haiyang,
Yao Ying,
Zhao Danyang,
Wang Shilei,
Pan Chuyue,
Duan Xubin,
Gao Yingsheng,
Liu Jun,
Zhang Yufei,
Yang Song,
Qi LianWen,
Wang Lirui
Publication year - 2020
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.14316
Subject(s) - steatosis , lipidome , steatohepatitis , nonalcoholic fatty liver disease , fatty liver , biology , gut flora , microbiome , bacteroides , medicine , endocrinology , biochemistry , lipidomics , bioinformatics , disease , genetics , bacteria
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, administration of Bacteroides uniformis increased specific TGs, and decreased hepatic injury and inflammation in diet‐induced mice. Conclusions Overall, through multi‐omics integration, we identified a microbiota‐lipid axis promoting the initiation of NASH from isolated steatosis, which might provide a novel perspective on NASH pathogenesis and treatment.