水蛭口服治疗通过逆转肝硬化相关肝脏基因失调改善纤维化。

IF 5.1 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2025-09-22 DOI:10.1016/j.lfs.2025.123979

Satya Priya Sharma , Min-Gi Cha , Goo-Hyun Kwon , Seol Hee Song , Jeong Ha Park , Min Ju Kim , Jung A Eom , Kyeong Jin Lee , Sang Jun Yoon , Hyunjoon Park , Sung-Min Won , Ki-Kwang Oh , Young Lim Ham , Gwang Ho Baik , Dong Joon Kim , Ki Tae Suk

{"title":"水蛭口服治疗通过逆转肝硬化相关肝脏基因失调改善纤维化。","authors":"Satya Priya Sharma , Min-Gi Cha , Goo-Hyun Kwon , Seol Hee Song , Jeong Ha Park , Min Ju Kim , Jung A Eom , Kyeong Jin Lee , Sang Jun Yoon , Hyunjoon Park , Sung-Min Won , Ki-Kwang Oh , Young Lim Ham , Gwang Ho Baik , Dong Joon Kim , Ki Tae Suk","doi":"10.1016/j.lfs.2025.123979","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div><em>Bacteroides</em>-centric gut dysbiosis reported to exacerbates liver cirrhosis via inflammation and fibrosis, therefore utilizing <em>Bacteroides</em> species as microbiome-based therapeutic logical to mitigate disease progression.</div></div><div><h3>Materials and methods</h3><div>Feces were collected from 52 Healthy and 144 Liver cirrhosis individuals for V3-V4 dependent 16rRNA-bsed comparative metagenomics analysis, followed a by microbiome depleted and non-depleted DDC mice model to explain the role of <em>Bacteroidetes</em> phylum classified microbial species <em>P. plebeius</em> in liver fibrosis pathophysiological pathways.</div></div><div><h3>Results</h3><div><em>Bacteroides</em> presented cirrhosis-dependent decrease in human and animal microbiome, and negatively correlated to key molecular pattern associated with cirrhosis. <em>P. plebeius</em> significantly reduced in abundance and identified as a microbial biomarker for cirrhosis (AUC = 0.73) and treatment with <em>P. plebeius</em> significantly improved the levels of cirrhosis-related phenotypical and biochemical markers in the microbiome-depleted cirrhosis group. <em>P. plebeius</em> decrease the expression of <em>S100a9</em>, <em>CCR1</em>, <em>ADAM8</em>, <em>TREM2</em>, <em>ITGAM</em>, and <em>MYO5A</em> which are primarily responsible for inducing inflammation in liver cirrhosis. <em>P. plebeius</em> downregulated the fibrosis related genes expression including <em>CD51</em>, <em>PLAT</em>, <em>ITGA3</em>, <em>CXCR4</em>, and <em>TGFBR1</em> and gene related to extracellular matrix formation including <em>COL1A1</em>, <em>LTBP2</em>, <em>S100A6</em>, and <em>SMCO2</em>. Additionally, <em>P. plebeius</em> treatment decreased the expression of hepatotoxicity-related genes including <em>LPL</em>, <em>KRT18</em>, <em>ALDOA</em>, and <em>MCM10</em>, and increased the expression of <em>FABP1</em> and <em>RDX</em>. Additionally, <em>P. plebeius</em> normalized the expression of genes connected to two pathophysiological process including <em>TIMP4</em>, <em>TGFB3</em>, <em>S100A8</em>, <em>PLSCR1</em>, <em>MMP8</em>, <em>CXCL4</em>, and <em>BMP</em>.</div></div><div><h3>Conclusions</h3><div>Our study revealed <em>P. plebeius</em> as a multifaceted bio-therapeutic candidate that normalized dysregulated gene expression and reversed hepatic inflammation, fibrogenesis, and hepatotoxicity.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"381 ","pages":"Article 123979"},"PeriodicalIF":5.1000,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Phocaeicola plebeius oral treatment improve fibrosis by reversing cirrhosis-related hepatic gene dysregulation\",\"authors\":\"Satya Priya Sharma , Min-Gi Cha , Goo-Hyun Kwon , Seol Hee Song , Jeong Ha Park , Min Ju Kim , Jung A Eom , Kyeong Jin Lee , Sang Jun Yoon , Hyunjoon Park , Sung-Min Won , Ki-Kwang Oh , Young Lim Ham , Gwang Ho Baik , Dong Joon Kim , Ki Tae Suk\",\"doi\":\"10.1016/j.lfs.2025.123979\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div><em>Bacteroides</em>-centric gut dysbiosis reported to exacerbates liver cirrhosis via inflammation and fibrosis, therefore utilizing <em>Bacteroides</em> species as microbiome-based therapeutic logical to mitigate disease progression.</div></div><div><h3>Materials and methods</h3><div>Feces were collected from 52 Healthy and 144 Liver cirrhosis individuals for V3-V4 dependent 16rRNA-bsed comparative metagenomics analysis, followed a by microbiome depleted and non-depleted DDC mice model to explain the role of <em>Bacteroidetes</em> phylum classified microbial species <em>P. plebeius</em> in liver fibrosis pathophysiological pathways.</div></div><div><h3>Results</h3><div><em>Bacteroides</em> presented cirrhosis-dependent decrease in human and animal microbiome, and negatively correlated to key molecular pattern associated with cirrhosis. <em>P. plebeius</em> significantly reduced in abundance and identified as a microbial biomarker for cirrhosis (AUC = 0.73) and treatment with <em>P. plebeius</em> significantly improved the levels of cirrhosis-related phenotypical and biochemical markers in the microbiome-depleted cirrhosis group. <em>P. plebeius</em> decrease the expression of <em>S100a9</em>, <em>CCR1</em>, <em>ADAM8</em>, <em>TREM2</em>, <em>ITGAM</em>, and <em>MYO5A</em> which are primarily responsible for inducing inflammation in liver cirrhosis. <em>P. plebeius</em> downregulated the fibrosis related genes expression including <em>CD51</em>, <em>PLAT</em>, <em>ITGA3</em>, <em>CXCR4</em>, and <em>TGFBR1</em> and gene related to extracellular matrix formation including <em>COL1A1</em>, <em>LTBP2</em>, <em>S100A6</em>, and <em>SMCO2</em>. Additionally, <em>P. plebeius</em> treatment decreased the expression of hepatotoxicity-related genes including <em>LPL</em>, <em>KRT18</em>, <em>ALDOA</em>, and <em>MCM10</em>, and increased the expression of <em>FABP1</em> and <em>RDX</em>. Additionally, <em>P. plebeius</em> normalized the expression of genes connected to two pathophysiological process including <em>TIMP4</em>, <em>TGFB3</em>, <em>S100A8</em>, <em>PLSCR1</em>, <em>MMP8</em>, <em>CXCL4</em>, and <em>BMP</em>.</div></div><div><h3>Conclusions</h3><div>Our study revealed <em>P. plebeius</em> as a multifaceted bio-therapeutic candidate that normalized dysregulated gene expression and reversed hepatic inflammation, fibrogenesis, and hepatotoxicity.</div></div>\",\"PeriodicalId\":18122,\"journal\":{\"name\":\"Life sciences\",\"volume\":\"381 \",\"pages\":\"Article 123979\"},\"PeriodicalIF\":5.1000,\"publicationDate\":\"2025-09-22\",\"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/S0024320525006150\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Life sciences","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0024320525006150","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

摘要

背景：据报道，以拟杆菌为中心的肠道生态失调会通过炎症和纤维化加剧肝硬化，因此利用拟杆菌作为基于微生物组的治疗逻辑来缓解疾病进展。材料与方法：收集52例健康和144例肝硬化患者的粪便，进行V3-V4依赖16rrna的比较宏基因组学分析，建立微生物组缺失和非缺失DDC小鼠模型，解释拟杆菌门分类微生物种plebeius在肝纤维化病理生理通路中的作用。结果：拟杆菌在人和动物微生物组中呈肝硬化依赖性减少，并与肝硬化相关的关键分子模式呈负相关。plebeius丰度显著降低，并被确定为肝硬化的微生物生物标志物（AUC = 0.73），在微生物组缺失的肝硬化组中，plebeius治疗显著改善了肝硬化相关表型和生化标志物的水平。P. plebeius降低了S100a9、CCR1、ADAM8、TREM2、ITGAM和MYO5A的表达，这些基因在肝硬化中主要负责诱导炎症。plebeius下调CD51、PLAT、ITGA3、CXCR4、TGFBR1等纤维化相关基因和COL1A1、LTBP2、S100A6、SMCO2等细胞外基质形成相关基因的表达。此外，plebeius处理降低了肝毒性相关基因LPL、KRT18、ALDOA和MCM10的表达，并增加了FABP1和RDX的表达。此外，plebeius还使TIMP4、TGFB3、S100A8、PLSCR1、MMP8、CXCL4和BMP等两个病理生理过程相关基因的表达正常化。结论：我们的研究揭示了plebeius是一种多方面的生物治疗候选者，可以使失调的基因表达正常化，逆转肝脏炎症、纤维化和肝毒性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Phocaeicola plebeius oral treatment improve fibrosis by reversing cirrhosis-related hepatic gene dysregulation

Background

Bacteroides-centric gut dysbiosis reported to exacerbates liver cirrhosis via inflammation and fibrosis, therefore utilizing Bacteroides species as microbiome-based therapeutic logical to mitigate disease progression.

Materials and methods

Feces were collected from 52 Healthy and 144 Liver cirrhosis individuals for V3-V4 dependent 16rRNA-bsed comparative metagenomics analysis, followed a by microbiome depleted and non-depleted DDC mice model to explain the role of Bacteroidetes phylum classified microbial species P. plebeius in liver fibrosis pathophysiological pathways.

Results

Bacteroides presented cirrhosis-dependent decrease in human and animal microbiome, and negatively correlated to key molecular pattern associated with cirrhosis. P. plebeius significantly reduced in abundance and identified as a microbial biomarker for cirrhosis (AUC = 0.73) and treatment with P. plebeius significantly improved the levels of cirrhosis-related phenotypical and biochemical markers in the microbiome-depleted cirrhosis group. P. plebeius decrease the expression of S100a9, CCR1, ADAM8, TREM2, ITGAM, and MYO5A which are primarily responsible for inducing inflammation in liver cirrhosis. P. plebeius downregulated the fibrosis related genes expression including CD51, PLAT, ITGA3, CXCR4, and TGFBR1 and gene related to extracellular matrix formation including COL1A1, LTBP2, S100A6, and SMCO2. Additionally, P. plebeius treatment decreased the expression of hepatotoxicity-related genes including LPL, KRT18, ALDOA, and MCM10, and increased the expression of FABP1 and RDX. Additionally, P. plebeius normalized the expression of genes connected to two pathophysiological process including TIMP4, TGFB3, S100A8, PLSCR1, MMP8, CXCL4, and BMP.

Conclusions

Our study revealed P. plebeius as a multifaceted bio-therapeutic candidate that normalized dysregulated gene expression and reversed hepatic inflammation, fibrogenesis, and hepatotoxicity.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

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.