Revealing the impact of gut microbiota-derived metabolites on depression through network pharmacology
A total of 208 metabolites and 223 targets were initially extracted from the gutMGene v1.0 database. In addition, 1,630 and 1,321 targets were identified using the Similarity Ensemble Approach and Swiss Target Prediction databases, respectively, resulting in 921 overlapping targets. By integrating d...
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Taylor & Francis Group
2025-12-01
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| Series: | Artificial Cells, Nanomedicine, and Biotechnology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/21691401.2025.2531752 |
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| author | Si Su Tengarile A Ruhan A Riga Wu Lisi Wei La Ta Wenfeng Huo Lijun Tong Jing Zhang Rilebagen Hu Li Li |
| author_facet | Si Su Tengarile A Ruhan A Riga Wu Lisi Wei La Ta Wenfeng Huo Lijun Tong Jing Zhang Rilebagen Hu Li Li |
| author_sort | Si Su |
| collection | DOAJ |
| description | A total of 208 metabolites and 223 targets were initially extracted from the gutMGene v1.0 database. In addition, 1,630 and 1,321 targets were identified using the Similarity Ensemble Approach and Swiss Target Prediction databases, respectively, resulting in 921 overlapping targets. By integrating data from gutMGenev1.0, 13 core targets were finally identified. A microbiota–metabolite–target–signal pathway–disease network was constructed using Cytoscape 3.9.1, revealing 15 metabolites associated with the IL-17, TLR, and PI3K-Akt signalling pathways. Among these, five metabolites exhibited favourable drug similarity and acceptable toxicological profiles. Molecular docking confirmed the stable binding of two key metabolites—succinate and phenylacetylglutamine—to their respective targets. The results showed that succinate and phenylacetylglutamine demonstrated strong binding affinities to IL-1β and GSK3B, both involved in the IL-17, TLR, and PI3K-Akt signalling pathways. IL-17 and TLR4, as important pro-inflammatory cytokines, are closely associated with the development of depression, while the PI3K/AKT signalling pathway plays a key role in its pathogenesis. The present study reveals the potential mechanisms by which gut microbiota influence MDD and provides a scientific basis and a comprehensive research framework for future investigations. |
| format | Article |
| id | doaj-art-0f34693a8fb04b4fbe1ff5659491f863 |
| institution | DOAJ |
| issn | 2169-1401 2169-141X |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
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| series | Artificial Cells, Nanomedicine, and Biotechnology |
| spelling | doaj-art-0f34693a8fb04b4fbe1ff5659491f8632025-08-20T02:45:42ZengTaylor & Francis GroupArtificial Cells, Nanomedicine, and Biotechnology2169-14012169-141X2025-12-0153132734210.1080/21691401.2025.2531752Revealing the impact of gut microbiota-derived metabolites on depression through network pharmacologySi Su0Tengarile A1Ruhan A2Riga Wu3Lisi Wei4La Ta5Wenfeng Huo6Lijun Tong7Jing Zhang8Rilebagen Hu9Li Li10Faculty of Mongolian Medicine, Inner Mongolia Medical University, Hohhot, Inner Mongolia, ChinaFaculty of Mongolian Medicine, Inner Mongolia Medical University, Hohhot, Inner Mongolia, ChinaFaculty of Mongolian Medicine, Inner Mongolia Medical University, Hohhot, Inner Mongolia, ChinaFaculty of Mongolian Medicine, Inner Mongolia Medical University, Hohhot, Inner Mongolia, ChinaFaculty of Mongolian Medicine, Inner Mongolia Medical University, Hohhot, Inner Mongolia, ChinaFaculty of Mongolian Medicine, Inner Mongolia Medical University, Hohhot, Inner Mongolia, ChinaFaculty of Mongolian Medicine, Inner Mongolia Medical University, Hohhot, Inner Mongolia, ChinaFaculty of Mongolian Medicine, Inner Mongolia Medical University, Hohhot, Inner Mongolia, ChinaBasic Medical Faculty, Inner Mongolia Medical University, Hohhot, Inner Mongolia, ChinaFaculty of Mongolian Medicine, Inner Mongolia Medical University, Hohhot, Inner Mongolia, ChinaBasic Medical Faculty, Inner Mongolia Medical University, Hohhot, Inner Mongolia, ChinaA total of 208 metabolites and 223 targets were initially extracted from the gutMGene v1.0 database. In addition, 1,630 and 1,321 targets were identified using the Similarity Ensemble Approach and Swiss Target Prediction databases, respectively, resulting in 921 overlapping targets. By integrating data from gutMGenev1.0, 13 core targets were finally identified. A microbiota–metabolite–target–signal pathway–disease network was constructed using Cytoscape 3.9.1, revealing 15 metabolites associated with the IL-17, TLR, and PI3K-Akt signalling pathways. Among these, five metabolites exhibited favourable drug similarity and acceptable toxicological profiles. Molecular docking confirmed the stable binding of two key metabolites—succinate and phenylacetylglutamine—to their respective targets. The results showed that succinate and phenylacetylglutamine demonstrated strong binding affinities to IL-1β and GSK3B, both involved in the IL-17, TLR, and PI3K-Akt signalling pathways. IL-17 and TLR4, as important pro-inflammatory cytokines, are closely associated with the development of depression, while the PI3K/AKT signalling pathway plays a key role in its pathogenesis. The present study reveals the potential mechanisms by which gut microbiota influence MDD and provides a scientific basis and a comprehensive research framework for future investigations.https://www.tandfonline.com/doi/10.1080/21691401.2025.2531752Major depressive disorder (MDD)network pharmacologyprevotellaceaelachnospiraceaesuccinatephenylacetylglutamine |
| spellingShingle | Si Su Tengarile A Ruhan A Riga Wu Lisi Wei La Ta Wenfeng Huo Lijun Tong Jing Zhang Rilebagen Hu Li Li Revealing the impact of gut microbiota-derived metabolites on depression through network pharmacology Artificial Cells, Nanomedicine, and Biotechnology Major depressive disorder (MDD) network pharmacology prevotellaceae lachnospiraceae succinate phenylacetylglutamine |
| title | Revealing the impact of gut microbiota-derived metabolites on depression through network pharmacology |
| title_full | Revealing the impact of gut microbiota-derived metabolites on depression through network pharmacology |
| title_fullStr | Revealing the impact of gut microbiota-derived metabolites on depression through network pharmacology |
| title_full_unstemmed | Revealing the impact of gut microbiota-derived metabolites on depression through network pharmacology |
| title_short | Revealing the impact of gut microbiota-derived metabolites on depression through network pharmacology |
| title_sort | revealing the impact of gut microbiota derived metabolites on depression through network pharmacology |
| topic | Major depressive disorder (MDD) network pharmacology prevotellaceae lachnospiraceae succinate phenylacetylglutamine |
| url | https://www.tandfonline.com/doi/10.1080/21691401.2025.2531752 |
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