Pien Tze Huang Protects Against Non-Alcoholic Steatohepatitis by Modulating the Gut Microbiota and Metabolites in Mice

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外文摘要：Non-alcoholic steatohepatitis(NASH)is a severe form of non-alcoholic fatty liver disease without effec-tive treatment.The traditional Chinese medicine formulation Pien Tze Huang(PTH)can suppress inflam-matory diseases.Here,we evaluate the effects of PTH on the evolution of NASH and its underlying mechanisms.We found that PTH prevented the development of steatohepatitis induced by various diet-ary models,including a high-fat high-cholesterol(HFHC)diet,choline-deficient high-fat diet(CD-HFD),and methionine-and choline-deficient(MCD)diet,along with significant suppression of liver injury,hepa-tic triglyceride,and lipid peroxidation.Moreover,ten days of PTH treatment after the onset of NASH sig-nificantly ameliorated MCD diet-induced steatosis and liver injury in mice.Through the metagenomic sequencing of stool samples,we found that PTH administration restored the gut microbiota with enrich-ment of probiotics including Lactobacillus acidophilus(L.acidophilus),Lactobacillus plantarum,Lactococcus lactis,and Bacillus subtilis.The enriched L.acidophilus prevented MCD diet-induced steatohepatitis.In addition,PTH restored the gut barrier function in mice with steatohepatitis,as evidenced by reduced intestinal permeability,decreased serum lipopolysaccharides(LPS)level,and increased epithelial tight-junction protein E-cadherin expression.Our metabolomic analysis via liquid chromatography-mass spec-trometry profiling identified the alteration in the metabolism of bile acids in the portal vein of PTH-treated mice.We further confirmed that an intact gut microbiota is necessary for PTH to exhibit anti-steatohepatitis effects.In conclusion,PTH protects against steatohepatitis development by modulating the gut microbiota and metabolites.PTH is a potential promising prophylactic and therapeutic option for patients with NASH.

外文关键词：

Pien Tze HuangNon-alcoholic steatohepatitisGut barrier functionGut microbiota

作者：

Xianyi Zeng、Xiang Zhang、Hao Su、Hongyan Gou、Harry Cheuk-Hay Lau、Xiaoxu Hu、Ziheng Huang、Yan Li、Jun Yu

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作者单位：

Shenzhen Research Institute,The Chinese University of Hong Kong,Shenzhen 518057,China

Department of Medicine and Therapeutics,Institute of Digestive Disease,State Key Laboratory of Digestive Disease,Li Ka Shing Institute of Health Sciences,The Chinese University of Hong Kong,Hong Kong 999077,China

基金：

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaResearch Grants Council-General Research FundResearch Grants Council-General Research FundHealth and Medical Research Fund,Hong KongVice-Chancellor's Discretionary Fund CUHK

项目编号：

8210335582222901RGC-GRF1411742208191336

出版年：

2024

DOI：

10.1016/j.eng.2022.10.010

工程(英文)

CSTPCDEI

ISSN：2095-8099

年,卷(期)：2024.35(4)