Bifidobacterium bifidum 1007478 derived indole-3-lactic acid alleviates NASH via an aromatic hydrocarbon receptor-dependent pathway in zebrafish

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2025-03-10 DOI:10.1016/j.lfs.2025.123557

Chao Tian , Shizhou Deng , Zhao Zhang , Kangdi Zheng , Lai Wei

{"title":"Bifidobacterium bifidum 1007478 derived indole-3-lactic acid alleviates NASH via an aromatic hydrocarbon receptor-dependent pathway in zebrafish","authors":"Chao Tian , Shizhou Deng , Zhao Zhang , Kangdi Zheng , Lai Wei","doi":"10.1016/j.lfs.2025.123557","DOIUrl":null,"url":null,"abstract":"<div><h3>Aims</h3><div>This study investigates the potential of <em>Bifidobacterium bifidum</em> 1007478 (BB478) and its metabolite indole-3-lactic acid (ILA) in alleviating non-alcoholic steatohepatitis (NASH) induced by a high-fat diet (HFD) and fructose exposure.</div></div><div><h3>Materials and methods</h3><div>A zebrafish model of NASH was established by exposure to HFD and fructose. BB478 was administered, and the effects on liver lipid accumulation, oxidative stress, and inflammation were assessed. ILA production by BB478 was confirmed, and its impact on hepatic lipogenesis and inflammatory pathways was evaluated. The involvement of the aromatic hydrocarbon receptor (AhR) was also examined using an AhR inhibitor.</div></div><div><h3>Key findings</h3><div>BB478 supplementation inhibited lipid accumulation in the liver, reduced triglycerides (TG) and total cholesterol (TC), and mitigated oxidative stress, as evidenced by lower levels of reactive oxygen species (ROS) and malondialdehyde (MDA). ILA, produced by BB478, could alleviate the hepatic damage and fat deposition in liver. Mechanistically, it suppressed hepatic lipogenesis by downregulating lipogenesis-related genes, including sterol response element binding protein 1 (SREBP1) and fatty acid synthase (FASN). ILA also inhibited the expression of pro-inflammatory cytokines to suppress inflammation. The therapeutic effects of ILA were reversed by the AhR inhibitor, indicating that ILA's actions are AhR-dependent.</div></div><div><h3>Significance</h3><div>These findings reveal the potential of ILA, produced by <em>Bifidobacterium bifidum</em>, as a therapeutic agent for NASH. The mechanistic insights into AhR-mediated effects provide a foundation for further exploration of ILA as a novel approach for managing liver diseases.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"369 ","pages":"Article 123557"},"PeriodicalIF":5.2000,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Life sciences","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0024320525001912","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}

引用次数: 0

Abstract

Aims

This study investigates the potential of Bifidobacterium bifidum 1007478 (BB478) and its metabolite indole-3-lactic acid (ILA) in alleviating non-alcoholic steatohepatitis (NASH) induced by a high-fat diet (HFD) and fructose exposure.

Materials and methods

A zebrafish model of NASH was established by exposure to HFD and fructose. BB478 was administered, and the effects on liver lipid accumulation, oxidative stress, and inflammation were assessed. ILA production by BB478 was confirmed, and its impact on hepatic lipogenesis and inflammatory pathways was evaluated. The involvement of the aromatic hydrocarbon receptor (AhR) was also examined using an AhR inhibitor.

Key findings

BB478 supplementation inhibited lipid accumulation in the liver, reduced triglycerides (TG) and total cholesterol (TC), and mitigated oxidative stress, as evidenced by lower levels of reactive oxygen species (ROS) and malondialdehyde (MDA). ILA, produced by BB478, could alleviate the hepatic damage and fat deposition in liver. Mechanistically, it suppressed hepatic lipogenesis by downregulating lipogenesis-related genes, including sterol response element binding protein 1 (SREBP1) and fatty acid synthase (FASN). ILA also inhibited the expression of pro-inflammatory cytokines to suppress inflammation. The therapeutic effects of ILA were reversed by the AhR inhibitor, indicating that ILA's actions are AhR-dependent.

Significance

These findings reveal the potential of ILA, produced by Bifidobacterium bifidum, as a therapeutic agent for NASH. The mechanistic insights into AhR-mediated effects provide a foundation for further exploration of ILA as a novel approach for managing liver diseases.

Abstract Image

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.