Abstract
This study aims to compare the gut microbiota and the profiles of human and microbial proteins in adolescents with bipolar depression (BD) and healthy controls (HCs), as well as to investigate the potential of gut-derived proteins as biomarkers for BD diagnosis. Fecal samples were collected from 15 adolescents with depressive episodes of BD and 58 healthy individuals, and fecal metaproteomics was used to assess changes in the gut environment. The results revealed an increased abundance of gut bacteria associated with lactate production and metabolism, such as Bifidobacteriaceae and Megasphaera, in BD patients. Additionally, there was a higher abundance of Alistipes, a bacterium linked to stress. Notably, the host proteins CELA2A, DEFA3, and KLK1 achieved high ROC-AUC values (0.905, 0.897, and 0.897) and PR-AUC values (0.978, 0.975, and 0.975),indicating their potential as diagnostic biomarkers for BD. In conclusion, we observed an increased abundance of Bifidobacteriaceae, Megasphaera, and Alistipes in adolescents with BD. We propose that CELA2A, DEFA3, and KLK1 could be potential biomarkers for BD, although further validation is required.
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Data availability
The mass spectrometry data generated in this study have been deposited in the Integrated Proteome Resources (iProX) database with the dataset identifier IPX0013607000. The data are publicly available at https://www.iprox.cn/page/project.html?id=IPX0013607000 and via the ProteomeXchange Consortium under the identifier PXD068942.
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ZZ and LY conceived and designed the study. YJ, FY, TY, YX, LX and LQ recruited participants and collected clinical samples. ZZ and TY performed data analysis and interpretation. ZZ drafted the original manuscript. YF, ZF and LY critically reviewed and revised the manuscript. LY supervised the study and acquired funding. All authors read and approved the final manuscript.
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All procedures performed in this study were conducted in accordance with the relevant guidelines and regulations. The study was approved by the Ethics Committee of The Fifth Affiliated Hospital of Sun Yat-sen University (Approval No. 2020-K32-1). Written informed consent was obtained from all participants and their legal guardians prior to participation in the study.
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Zhao, Z., Yang, F., Tan, Y. et al. Fecal metaproteomics reveals alterations in gut microbiota and intestinal proteins in adolescents with bipolar depression. Transl Psychiatry (2026). https://doi.org/10.1038/s41398-026-03899-6
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DOI: https://doi.org/10.1038/s41398-026-03899-6
