ORIGINAL RESEARCH article
Front. Psychiatry
Sec. Mood Disorders
This article is part of the Research TopicGut Microbiome Influences in Mood Disorders: Unveiling the Gut-Brain AxisView all 8 articles
Gut Microbiota and Metabolic Characteristics in Subthreshold Depression Based on Multi-Omics
Provisionally accepted
Jin Xian1,2
Ling Wang1RuPing Shang1
Mi Sun1
Xin Zhang1Hui-Juan Yu1
Cheng Bin2Shi-Jun Wang1*
Qi-wen Tan1,2*- 1Shandong University of Traditional Chinese Medicine, Jinan, China
- 2Shandong University of Traditional Chinese Medicine Affiliated Hospital, Jinan, China
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Background: Subthreshold depression (SD) is an intermediate state between normal mood and major depressive disorder (MDD), but its biological underpinnings remain insufficiently understood. Increasing evidence suggests that gut microbiota and host metabolic alterations may contribute to early depressive pathophysiology. Methods: We performed full-length 16S rRNA gene sequencing and LC–MS-based untargeted metabolomics on stool and plasma samples obtained from SD subjects and healthy controls. Microbial diversity, taxonomic composition, metabolic pathway alterations, and gut microbiota–metabolite associations were analyzed using bioinformatics pipelines, KEGG annotation, and Spearman correlation analysis. Results: SD patients exhibited marked gut microbial disturbances, including reduced microbial diversity and altered abundances of key genera such as decreased Eubacterium hallii group, Blautia, Dorea, and Agathobacter, and increased Escherichia–Shigella, Monoglobus, and Lachnoclostridium. Metabolomic profiling identified widespread metabolic perturbations, mainly affecting lipid metabolism, steroid hormone biosynthesis, and amino acid pathways. Exploratory correlation analysis indicated that beneficial taxa (e.g., Eubacterium hallii group and Blautia) were positively associated with specific glycerophospholipid and steroid hormone metabolites, whereas inverse associations were observed for other lipid-related metabolites. Conclusion: This integrative microbiome–metabolome analysis demonstrates that SD is accompanied by early disruptions in gut microbial composition and systemic metabolism, particularly within lipid-related pathways. These findings suggest that gut microbiota dysbiosis may reflect early metabolic dysregulation and depression-related biological vulnerability in SD and highlight the gut microbiota as a candidate biological target for early identification and intervention.
Keywords: gut brain axis, Gut Microbiota, Lipid Metabolism, microbiota–metabolite axis, Subthreshold depression
Received: 04 Dec 2025; Accepted: 30 Jan 2026.
Copyright: © 2026 Xian, Wang, Shang, Sun, Zhang, Yu, Bin, Wang and Tan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Shi-Jun Wang
Qi-wen Tan
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