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

Abstract

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.

A High-Fat Diet Increases Gut Microbiota Biodiversity and Energy Expenditure Due to Nutrient Difference

“…The Rikenellaceae RC9 gut group and Mucispirillum were identified by VIP predictive and LEfSe as having a higher relative abundance in the HFD group. Previous studies have reported that HFD enriched the abundance of both the Rikenellaceae RC9 gut group and Mucispirillum in the cecum [ 35 , 36 ], with Mucispirillum being correlated positively with the presence of non-alcoholic steatohepatitis. Compared with cecal microbiota, there were more OTUs observed in the colonic microbiota.…”

919 Syrup Alleviates Postpartum Depression by Modulating the Structure and Metabolism of Gut Microbes and Affecting the Function of the Hippocampal GABA/Glutamate System

“…Mucispirillum schaedleri , the sole known member of the phylum Deferribacteres that is present in the gut microbiota of both mice and humans, is known to express secretion systems and effector proteins that can modify the gene expression of the host mucosa. This suggests that Mucispirillum schaedleri interacts intimately with the host and may play a role in inflammation ( Caruso et al., 2019 ; Herp et al., 2019 ; Liu et al., 2019 ; Wu et al., 2020 ), metabolic homeostasis ( Qian et al., 2020 ; Wu et al., 2020 ), and stress ( Liu et al., 2019 ). Its clinical manifestations are disparate.…”

Untargeted and targeted metabolomics profiling reveals the underlying pathogenesis and abnormal arachidonic acid metabolism in laying hens with fatty liver hemorrhagic syndrome

“…The lack of protein in the high-energy low-protein diet might be the main reason for the reduced tyrosine. LysoPC, the oxidation product of low-density lipoprotein, can induce inflammation, autoimmune response and oxidative stress in various diseases including cancer, atherosclerosis, hyperlipidemia and nonalcoholic steatohepatitis ( Hsu et al., 2011 ; Qian et al., 2020 ). Increased levels of LysoPC (14:0), LysoPC (16:0) and LysoPE (16:0) were observed in the liver from FLHS group, which might indicate the disturbance in glycerophospholipid metabolism and increase the risk of FLHS.…”