Butyrate inhibits histone deacetylase 2 expression to alleviate liver fibrosis in biliary atresia.

IF 2 3区医学 Q2 PEDIATRICS

BMC Pediatrics Pub Date : 2025-04-12 DOI:10.1186/s12887-025-05635-3

Yilin Zhao, Xiaodan Xu, Shaowen Liu, Xueting Wang, Jiayinaxi Musha, Tengfei Li, Liang Ge, Yan Sun, Shujian Zhang, Li Zhao, Jianghua Zhan

{"title":"Butyrate inhibits histone deacetylase 2 expression to alleviate liver fibrosis in biliary atresia.","authors":"Yilin Zhao, Xiaodan Xu, Shaowen Liu, Xueting Wang, Jiayinaxi Musha, Tengfei Li, Liang Ge, Yan Sun, Shujian Zhang, Li Zhao, Jianghua Zhan","doi":"10.1186/s12887-025-05635-3","DOIUrl":null,"url":null,"abstract":"Background: Previous studies have found a reduction in butyrate-producing bacteria in the gut microbiota of infants with biliary atresia (BA). Butyrate is also an important inhibitor of histone deacetylase 2 (HDAC2). This study aims to explore how butyrate alleviates liver fibrosis in BA through HDAC2.Methods: Fibrosis-related pathways associated with butyrate were analyzed using the GSE46960 database. BA liver sections were used to validate factor expression. The effects of HDAC2 and butyrate and the pathway were performed in vitro experiments. Butyrate intervention was performed in bile duct ligation (BDL) mice, and alterations in the gut microbiota were analyzed using fecal 16S rRNA sequencing. The impact of butyrate and related pathways on liver fibrosis in BDL mice was further evaluated.Results: The IL-6/STAT3 pathway showed a clear correlation with butyrate in BA. HDAC2 promoted LX-2 activation via the IL-6/STAT3 pathway, while butyrate inhibited LX-2 activation by suppressing HDAC2. Butyrate not only alleviated liver fibrosis but also improved the gut microbiota structure in BDL mice.Conclusion: Butyrate may improve liver fibrosis in BA by regulating HDAC2 expression and modulating the IL-6/STAT3 pathway. Therefore, butyrate could serve as a promising therapeutic option for mitigating liver fibrosis in BA.","PeriodicalId":9144,"journal":{"name":"BMC Pediatrics","volume":"25 1","pages":"286"},"PeriodicalIF":2.0000,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11992845/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Pediatrics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12887-025-05635-3","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PEDIATRICS","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Previous studies have found a reduction in butyrate-producing bacteria in the gut microbiota of infants with biliary atresia (BA). Butyrate is also an important inhibitor of histone deacetylase 2 (HDAC2). This study aims to explore how butyrate alleviates liver fibrosis in BA through HDAC2.

Methods: Fibrosis-related pathways associated with butyrate were analyzed using the GSE46960 database. BA liver sections were used to validate factor expression. The effects of HDAC2 and butyrate and the pathway were performed in vitro experiments. Butyrate intervention was performed in bile duct ligation (BDL) mice, and alterations in the gut microbiota were analyzed using fecal 16S rRNA sequencing. The impact of butyrate and related pathways on liver fibrosis in BDL mice was further evaluated.

Results: The IL-6/STAT3 pathway showed a clear correlation with butyrate in BA. HDAC2 promoted LX-2 activation via the IL-6/STAT3 pathway, while butyrate inhibited LX-2 activation by suppressing HDAC2. Butyrate not only alleviated liver fibrosis but also improved the gut microbiota structure in BDL mice.

Conclusion: Butyrate may improve liver fibrosis in BA by regulating HDAC2 expression and modulating the IL-6/STAT3 pathway. Therefore, butyrate could serve as a promising therapeutic option for mitigating liver fibrosis in BA.

查看原文本刊更多论文

丁酸抑制组蛋白去乙酰化酶2表达减轻胆道闭锁肝纤维化。

背景：先前的研究发现，胆道闭锁（BA）婴儿肠道微生物群中产生丁酸盐的细菌减少。丁酸盐也是组蛋白去乙酰化酶2 （HDAC2）的重要抑制剂。本研究旨在探讨丁酸盐如何通过HDAC2减轻BA肝纤维化。方法：使用GSE46960数据库分析与丁酸盐相关的纤维化相关通路。BA肝切片用于验证因子表达。体外实验考察了HDAC2和丁酸盐的作用及其途径。对胆管结扎（BDL）小鼠进行丁酸干预，并通过粪便16S rRNA测序分析肠道微生物群的变化。进一步评价丁酸酯及其相关通路对BDL小鼠肝纤维化的影响。结果：BA中IL-6/STAT3通路与丁酸盐有明显的相关性。HDAC2通过IL-6/STAT3途径促进LX-2的激活，而丁酸盐通过抑制HDAC2抑制LX-2的激活。丁酸盐不仅能减轻BDL小鼠的肝纤维化，还能改善肠道菌群结构。结论：丁酸盐可能通过调节hdac - 2表达和IL-6/STAT3通路改善BA大鼠肝纤维化。因此，丁酸盐可作为缓解BA肝纤维化的一种有前景的治疗选择。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

BMC Pediatrics PEDIATRICS-

CiteScore

3.70

自引率

4.20%

发文量

683

审稿时长

3-8 weeks

期刊介绍： BMC Pediatrics is an open access journal publishing peer-reviewed research articles in all aspects of health care in neonates, children and adolescents, as well as related molecular genetics, pathophysiology, and epidemiology.