Butyrate inhibits histone deacetylase 2 expression to alleviate liver fibrosis in biliary atresia
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 thr...
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BMC
2025-04-01
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| Series: | BMC Pediatrics |
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| Online Access: | https://doi.org/10.1186/s12887-025-05635-3 |
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| author | Yilin Zhao Xiaodan Xu Shaowen Liu Xueting Wang Jiayinaxi Musha Tengfei Li Liang Ge Yan Sun Shujian Zhang Li Zhao Jianghua Zhan |
| author_facet | Yilin Zhao Xiaodan Xu Shaowen Liu Xueting Wang Jiayinaxi Musha Tengfei Li Liang Ge Yan Sun Shujian Zhang Li Zhao Jianghua Zhan |
| author_sort | Yilin Zhao |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d9f2c0f557ff4358b11baebf24f95201 |
| institution | OA Journals |
| issn | 1471-2431 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Pediatrics |
| spelling | doaj-art-d9f2c0f557ff4358b11baebf24f952012025-08-20T02:16:07ZengBMCBMC Pediatrics1471-24312025-04-0125111210.1186/s12887-025-05635-3Butyrate inhibits histone deacetylase 2 expression to alleviate liver fibrosis in biliary atresiaYilin Zhao0Xiaodan Xu1Shaowen Liu2Xueting Wang3Jiayinaxi Musha4Tengfei Li5Liang Ge6Yan Sun7Shujian Zhang8Li Zhao9Jianghua Zhan10Graduate College, Tianjin Medical UniversityDepartment of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyGraduate College, Tianjin Medical UniversityDepartment of Pediatric Surgery, Xinjiang Yili Friendship HospitalGraduate College, Tianjin Medical UniversityGraduate College, Tianjin Medical UniversityDepartment of General Surgery, Tianjin Children’s HospitalDepartment of General Surgery, Tianjin Children’s HospitalDepartment of General Surgery, Tianjin Children’s HospitalDepartment of Pathology, Tianjin Children’s HospitalDepartment of General Surgery, Tianjin Children’s HospitalAbstract 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.https://doi.org/10.1186/s12887-025-05635-3Biliary atresiaFibrosisButyrateHDAC2IL-6STAT3 |
| spellingShingle | Yilin Zhao Xiaodan Xu Shaowen Liu Xueting Wang Jiayinaxi Musha Tengfei Li Liang Ge Yan Sun Shujian Zhang Li Zhao Jianghua Zhan Butyrate inhibits histone deacetylase 2 expression to alleviate liver fibrosis in biliary atresia BMC Pediatrics Biliary atresia Fibrosis Butyrate HDAC2 IL-6 STAT3 |
| title | Butyrate inhibits histone deacetylase 2 expression to alleviate liver fibrosis in biliary atresia |
| title_full | Butyrate inhibits histone deacetylase 2 expression to alleviate liver fibrosis in biliary atresia |
| title_fullStr | Butyrate inhibits histone deacetylase 2 expression to alleviate liver fibrosis in biliary atresia |
| title_full_unstemmed | Butyrate inhibits histone deacetylase 2 expression to alleviate liver fibrosis in biliary atresia |
| title_short | Butyrate inhibits histone deacetylase 2 expression to alleviate liver fibrosis in biliary atresia |
| title_sort | butyrate inhibits histone deacetylase 2 expression to alleviate liver fibrosis in biliary atresia |
| topic | Biliary atresia Fibrosis Butyrate HDAC2 IL-6 STAT3 |
| url | https://doi.org/10.1186/s12887-025-05635-3 |
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