Alterations in fecal microbiota composition and cytokine expression profiles in adolescents with depression: a case-control study

Abstract Emerging evidence has highlighted that altered gut microbiota are associated with the onset and progression of depression via regulating the gut-brain axis. However, existing research has predominantly focused on children and adults, frequently neglecting adolescent depression. Given the ri...

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Main Authors: Yiwen Cheng, Zhangcheng Zhu, Zhi Yang, Xia Liu, Xiulian Qian, Juntao Zhu, Xinzhu Hu, Peijie Jiang, Tingting Cui, Yuwei Wang, Wenwen Ding, Wenhui Lei, Jie Gao, Jingchen Zhang, Yating Li, Li Shao, Zongxin Ling, Weiming Hu
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-97369-6
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author Yiwen Cheng
Zhangcheng Zhu
Zhi Yang
Xia Liu
Xiulian Qian
Juntao Zhu
Xinzhu Hu
Peijie Jiang
Tingting Cui
Yuwei Wang
Wenwen Ding
Wenhui Lei
Jie Gao
Jingchen Zhang
Yating Li
Li Shao
Zongxin Ling
Weiming Hu
author_facet Yiwen Cheng
Zhangcheng Zhu
Zhi Yang
Xia Liu
Xiulian Qian
Juntao Zhu
Xinzhu Hu
Peijie Jiang
Tingting Cui
Yuwei Wang
Wenwen Ding
Wenhui Lei
Jie Gao
Jingchen Zhang
Yating Li
Li Shao
Zongxin Ling
Weiming Hu
author_sort Yiwen Cheng
collection DOAJ
description Abstract Emerging evidence has highlighted that altered gut microbiota are associated with the onset and progression of depression via regulating the gut-brain axis. However, existing research has predominantly focused on children and adults, frequently neglecting adolescent depression. Given the rising prevalence and substantial impact of adolescent depression on functional impairment and suicidality, it is essential to focus more on this age group. In this study, we examined the fecal microbiota and inflammatory profiles of 99 depressed adolescents and 106 age-matched healthy controls using Illumina NovaSeq sequencing and multiplex immunoassays, respectively. Our findings revealed lower bacterial α-diversity and richness, alongside altered β-diversity in adolescents with depression. Gut dysbiosis associated with adolescent depression was characterized by increased pro-inflammatory genera such as Streptococcus and decreased anti-inflammatory genera like Faecalibacterium. These differential genera may serve as potential non-invasive biomarkers for adolescent depression, either individually or in combination. We also observed disruptions in the inferred microbiota functions in adolescent depression-associated microbiota, particularly in glycolysis and gluconeogenesis. Additionally, depressed adolescents exhibited systemic immune dysfunction, with elevated levels of pro-inflammatory cytokines and chemokines, which showed significant correlations with the differential genera. Our study bridges the gap between children and adults by providing new insights into the fecal microbiota characteristics and their links to immune system disruptions in depressed adolescents, which offer new targets for the diagnosis and treatment of depression in this age group.
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spelling doaj-art-8015b2f1f85249a89a00d21adaf2a6572025-08-20T02:28:05ZengNature PortfolioScientific Reports2045-23222025-04-0115111510.1038/s41598-025-97369-6Alterations in fecal microbiota composition and cytokine expression profiles in adolescents with depression: a case-control studyYiwen Cheng0Zhangcheng Zhu1Zhi Yang2Xia Liu3Xiulian Qian4Juntao Zhu5Xinzhu Hu6Peijie Jiang7Tingting Cui8Yuwei Wang9Wenwen Ding10Wenhui Lei11Jie Gao12Jingchen Zhang13Yating Li14Li Shao15Zongxin Ling16Weiming Hu17Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang UniversityDepartment of Preventive Medicine, School of Public Health and Management, Wenzhou Medical UniversityDepartment of Psychiatry, Quzhou Third HospitalDepartment of Intensive Care Unit, The First Affiliated Hospital, School of Medicine, Zhejiang UniversityDepartment of Psychiatry, Quzhou Third HospitalDepartment of Psychiatry, Quzhou Third HospitalDepartment of Psychiatry, Quzhou Third HospitalDepartment of Psychiatry, Quzhou Third HospitalDepartment of Psychiatry, Quzhou Third HospitalDepartment of Psychiatry, Quzhou Third HospitalDepartment of Anesthesiology, Affiliated Hospital of Nantong UniversityJinan Microecological Biomedicine Shandong LaboratoryCollaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang UniversityDepartment of Intensive Care Unit, The First Affiliated Hospital, School of Medicine, Zhejiang UniversityCollaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang UniversitySchool of Clinical Medicine, Institute of Hepatology and Metabolic Diseases, Hangzhou Normal University, The Affiliated Hospital of Hangzhou Normal UniversityCollaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang UniversityDepartment of Psychiatry, Quzhou Third HospitalAbstract Emerging evidence has highlighted that altered gut microbiota are associated with the onset and progression of depression via regulating the gut-brain axis. However, existing research has predominantly focused on children and adults, frequently neglecting adolescent depression. Given the rising prevalence and substantial impact of adolescent depression on functional impairment and suicidality, it is essential to focus more on this age group. In this study, we examined the fecal microbiota and inflammatory profiles of 99 depressed adolescents and 106 age-matched healthy controls using Illumina NovaSeq sequencing and multiplex immunoassays, respectively. Our findings revealed lower bacterial α-diversity and richness, alongside altered β-diversity in adolescents with depression. Gut dysbiosis associated with adolescent depression was characterized by increased pro-inflammatory genera such as Streptococcus and decreased anti-inflammatory genera like Faecalibacterium. These differential genera may serve as potential non-invasive biomarkers for adolescent depression, either individually or in combination. We also observed disruptions in the inferred microbiota functions in adolescent depression-associated microbiota, particularly in glycolysis and gluconeogenesis. Additionally, depressed adolescents exhibited systemic immune dysfunction, with elevated levels of pro-inflammatory cytokines and chemokines, which showed significant correlations with the differential genera. Our study bridges the gap between children and adults by providing new insights into the fecal microbiota characteristics and their links to immune system disruptions in depressed adolescents, which offer new targets for the diagnosis and treatment of depression in this age group.https://doi.org/10.1038/s41598-025-97369-6AdolescentDepressionGut microbiotaImmune dysfunctionFaecalibacterium
spellingShingle Yiwen Cheng
Zhangcheng Zhu
Zhi Yang
Xia Liu
Xiulian Qian
Juntao Zhu
Xinzhu Hu
Peijie Jiang
Tingting Cui
Yuwei Wang
Wenwen Ding
Wenhui Lei
Jie Gao
Jingchen Zhang
Yating Li
Li Shao
Zongxin Ling
Weiming Hu
Alterations in fecal microbiota composition and cytokine expression profiles in adolescents with depression: a case-control study
Scientific Reports
Adolescent
Depression
Gut microbiota
Immune dysfunction
Faecalibacterium
title Alterations in fecal microbiota composition and cytokine expression profiles in adolescents with depression: a case-control study
title_full Alterations in fecal microbiota composition and cytokine expression profiles in adolescents with depression: a case-control study
title_fullStr Alterations in fecal microbiota composition and cytokine expression profiles in adolescents with depression: a case-control study
title_full_unstemmed Alterations in fecal microbiota composition and cytokine expression profiles in adolescents with depression: a case-control study
title_short Alterations in fecal microbiota composition and cytokine expression profiles in adolescents with depression: a case-control study
title_sort alterations in fecal microbiota composition and cytokine expression profiles in adolescents with depression a case control study
topic Adolescent
Depression
Gut microbiota
Immune dysfunction
Faecalibacterium
url https://doi.org/10.1038/s41598-025-97369-6
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