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

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

  • BMC Pediatr. 2025 Apr 12;25(1):286. doi: 10.1186/s12887-025-05635-3.
Yilin Zhao # 1 2,  Xiaodan Xu # 3,  Shaowen Liu 1 2,  Xueting Wang 4,  Jiayinaxi Musha 1 2 5,  Tengfei Li 1 2,  Liang Ge 2,  Yan Sun 2,  Shujian Zhang 2,  Li Zhao 6,  Jianghua Zhan 7
Affiliations

Affiliations

  • 1 Graduate College, Tianjin Medical University, Tianjin, China.
  • 2 Department of General Surgery, Tianjin Children's Hospital, LongYan Road 238, Beichen District, Tianjin, 300134, P. R. China.
  • 3 Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
  • 4 Department of Pediatric Surgery, Xinjiang Yili Friendship Hospital, Yili, China.
  • 5 Department of Pediatric Surgery, Urumqi First People's Hospital (Urumqi Children's Hospital), Xinjiang, China.
  • 6 Department of Pathology, Tianjin Children's Hospital, Tianjin, China.
  • 7 Department of General Surgery, Tianjin Children's Hospital, LongYan Road 238, Beichen District, Tianjin, 300134, P. R. China. zhanjianghuatj@163.com.
  • # Contributed equally.
PMID: 40221650 DOI: 10.1186/s12887-025-05635-3
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.

Keywords

Biliary atresia; Butyrate; Fibrosis; HDAC2; IL-6; STAT3.

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