Integrative analysis reveals gut microbiota-associated host regulatory networks in liver fibrosis
4 affiliations
- 1Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
- 2Department of Gastroenterology, The First Affiliated Hospital of Shihezi University, Shihezi, Xinjiang, China
- 3Department of Infectious Diseases, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
- 4Department of Central Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
Abstract
Background: Gut microbiota-derived metabolites may contribute to liver fibrosis by affecting host inflammatory, metabolic, and epigenetic pathways. We aimed to identify microbiota-associated host genes shared across liver fibrosis of different etiologies.
Methods: Microbiota- and metabolite-associated host genes were obtained from gutMGene v2.0 and integrated with differentially expressed genes from two human liver transcriptomic datasets: GSE84044 for HBV-related fibrosis and GSE49541 for NAFLD-related fibrosis. Shared genes were analyzed using protein–protein interaction and functional enrichment analyses. Selected metabolite–protein interactions were assessed by molecular docking and molecular dynamics simulations. Two-sample Mendelian randomization was used to examine potential associations between candidate gene expression and liver fibrosis risk.
Results: Fourteen microbiota-associated genes were differentially expressed in both fibrosis cohorts, including CCL2, CCL20, CXCL6, PTGS2, HDAC2, HDAC3, ADRA2A, SOD1, PEMT, and GNMT. These genes were mainly associated with chemokine activity, histone deacetylation, and IL-17 and TNF signaling. Molecular docking suggested structural compatibility between phenylacetylglutamine and ADRA2A, while butyrate showed weaker predicted interactions with HDAC2 and HDAC3.Molecular dynamics analysis supported the stability of the ADRA2A–phenylacetylglutamine complex under the simulated conditions. Mendelian randomization identified nominal associations of HDAC3, CCL2, PTGS2, and VCL expression with liver fibrosis risk.
Conclusions: This study identified shared microbiota-associated host regulatory candidates in HBV- and NAFLD-related liver fibrosis.HDAC3 and ADRA2A may represent potential links between microbial metabolic signals and fibrotic responses, although further experimental validation is required.
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BibTeX
@article{peng2026integrative,
title = {{Integrative analysis reveals gut microbiota-associated host regulatory networks in liver fibrosis}},
author = {Shiyu Peng and Yingying Nie and Yuzhu Song and Han Ding and Huiling Cao and Hao Wu and Jianni Qi and Qiang Zhu},
journal = {Frontiers in Cellular and Infection Microbiology},
year = {2026},
month = oct,
doi = {10.3389/fcimb.2026.1963640},
url = {https://doi.org/10.3389/fcimb.2026.1963640},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Integrative analysis reveals gut microbiota-associated host regulatory networks in liver fibrosis
AU - Shiyu Peng
AU - Yingying Nie
AU - Yuzhu Song
AU - Han Ding
AU - Huiling Cao
AU - Hao Wu
AU - Jianni Qi
AU - Qiang Zhu
PY - 2026
DA - 2026/10/13
JO - Frontiers in Cellular and Infection Microbiology
DO - 10.3389/fcimb.2026.1963640
UR - https://doi.org/10.3389/fcimb.2026.1963640
AB - Background: Gut microbiota-derived metabolites may contribute to liver fibrosis by affecting host inflammatory, metabolic, and epigenetic pathways. We aimed to identify microbiota-associated host genes shared across liver fibrosis of different etiologies. Methods: Microbiota- and metabolite-associated host genes were obtained from gutMGene v2.0 and integrated with differentially expressed genes from two human liver transcriptomic datasets: GSE84044 for HBV-related fibrosis and GSE49541 for NAFLD-related fibrosis. Shared genes were analyzed using protein–protein interaction and functional enrichment analyses. Selected metabolite–protein interactions were assessed by molecular docking and molecular dynamics simulations. Two-sample Mendelian randomization was used to examine potential associations between candidate gene expression and liver fibrosis risk. Results: Fourteen microbiota-associated genes were differentially expressed in both fibrosis cohorts, including CCL2, CCL20, CXCL6, PTGS2, HDAC2, HDAC3, ADRA2A, SOD1, PEMT, and GNMT. These genes were mainly associated with chemokine activity, histone deacetylation, and IL-17 and TNF signaling. Molecular docking suggested structural compatibility between phenylacetylglutamine and ADRA2A, while butyrate showed weaker predicted interactions with HDAC2 and HDAC3.Molecular dynamics analysis supported the stability of the ADRA2A–phenylacetylglutamine complex under the simulated conditions. Mendelian randomization identified nominal associations of HDAC3, CCL2, PTGS2, and VCL expression with liver fibrosis risk. Conclusions: This study identified shared microbiota-associated host regulatory candidates in HBV- and NAFLD-related liver fibrosis.HDAC3 and ADRA2A may represent potential links between microbial metabolic signals and fibrotic responses, although further experimental validation is required.
SN - 2235-2988
ER -