Hydrogen inhalation ameliorates hepatic inflammation and modulates gut microbiota in rats with high-fat diet-induced non-alcoholic fatty liver disease

Boyan Liu, Jun-Li Xue, Min Zhao, Qianqian Gu, Shuchun Qin, Xiaoyi Zhang, Xiubin Jia, Yunbo Xie, Yunchao Liu

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DOI: 10.1016/j.ejphar.2023.175698 DOI is the universal ID for this study.

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Nonalcoholic fatty liver disease (NAFLD) is a multisystem metabolic disease associated with gut microflora dysbiosis and inflammation. Hydrogen (H2) is a novel and effective antiinflammatory agent. The present study was aimed to clarify the effects of 4% H2 inhalation on NAFLD and its mechanism of action. Sprague-Dawley rats were fed a high-fat diet for 10 weeks to induce NAFLD. Rats in treatment group inhaled 4% H2 each day for 2 h. The protective effects on hepatic histopathology, glucose tolerance, inflammatory markers, and intestinal epithelial tight junctions were assessed. Transcriptome sequencing of liver and 16 S-seq of cecal contents were also performed to explore the related mechanisms of H2 inhalation. H2 improved the hepatic histological changes and glucose tolerance, decreased the liver function parameters of plasma alanine aminotransferase and aspartate aminotransferase, and relieved liver inflammation. Liver transcriptomic data suggested that H2 treatment significantly downregulated inflammatory response genes, and the lipopolysaccharide (LPS)/Toll-like receptor (TLR) 4/nuclear transcription factor kappa B (NF-κB) signaling pathway might be involved, and the expressions of critical proteins were further validated. Meanwhile, the plasma LPS level was significantly decreased by the H2 intervention. H2 also improved the intestinal tight junction barrier by enhancing the expressions of zonula occludens-1 and occluding. Based on 16S rRNA sequencing, H2 altered the composition of gut microbiota, improving the relative abundance of Bacteroidetes-to-Firmicutes. Collectively, our data show that H2 could prevent NAFLD induced by high-fat diet, and the anti-NAFLD effect is associated with the modulation of gut microbiota and inhibition of LPS/TLR4/NF-κB inflammatory pathway.

Publish Year 2023
Country China
Rank Positive
Journal European Journal of Pharmacology
Primary Topic Liver
Secondary TopicLiver Disease
Model Rat
Tertiary TopicFatty Liver Disease (Nonalcoholic)
Vehicle Gas
pH N/A
Application Inhalation