Chronic stress is associated with altered gut microbiota profile and relevant metabolites in adolescents

Abstract Background Gut microbiota and microbiota-derived metabolites have been implicated in the regulation of stress-related diseases, yet their associations with chronic stress in adolescents remain unclear. Multi-omics studies on this topic in adolescents are still limited. This study aimed to c...

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Main Authors: Li Ying, Wang Yuhao, He Yafang, Lan Jiao, Dang Lina, Song Qinze, Yang Chenghai, Zhao Shaoxiong, Gu Yuexi, Shen Mingwang, Cai Zelin, Wang Chuangchuang, Guo Zihan, Liu Xin, Ma Lu, Zhang Lei
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Language:English
Published: BMC 2025-07-01
Series:BMC Microbiology
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Online Access:https://doi.org/10.1186/s12866-025-04094-1
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author Li Ying
Wang Yuhao
He Yafang
Lan Jiao
Dang Lina
Song Qinze
Yang Chenghai
Zhao Shaoxiong
Gu Yuexi
Shen Mingwang
Cai Zelin
Wang Chuangchuang
Guo Zihan
Liu Xin
Ma Lu
Zhang Lei
author_facet Li Ying
Wang Yuhao
He Yafang
Lan Jiao
Dang Lina
Song Qinze
Yang Chenghai
Zhao Shaoxiong
Gu Yuexi
Shen Mingwang
Cai Zelin
Wang Chuangchuang
Guo Zihan
Liu Xin
Ma Lu
Zhang Lei
author_sort Li Ying
collection DOAJ
description Abstract Background Gut microbiota and microbiota-derived metabolites have been implicated in the regulation of stress-related diseases, yet their associations with chronic stress in adolescents remain unclear. Multi-omics studies on this topic in adolescents are still limited. This study aimed to characterize gut microbiota and metabolites in adolescents under chronic stress. Methods In this cross-sectional study, we assessed chronic stress in 124 adolescents aged 12–16 years using the Adolescent Life Events Scale and the Study Stress Scale. Participants were stratified by stress level into low (n = 42), medium (n = 41), and high stress (n = 41) groups. Fecal samples were collected from all participants for 16S rRNA gene sequencing. Subsequently, a subset of 30 adolescents with high stress and 29 low stress adolescents underwent metagenomic sequencing and untargeted metabolomics. Results Adolescents experiencing high-chronic stress showed lower alpha diversity, differential beta diversity, and a more complicated microbial network compared to those experiencing lower stress. Spearman’s rank correlation and Kruskal-Wallis test identified five genera with decreased abundances in high stress adolescents, including Faecalibacterium, Bacteroides, Akkermansia, Lachnospiraceae unclassified, and Ruminococcus (P fdr<0.05). Additionally, 12 species showed decreased abundances and 5 increased abundances, and logistic regression analysis further revealed that the relative abundances of Bifidobacterium catenulatum, Streptococcus suis, Ruminococcus sp. CAG 108, and Phascolarctobacterium faecium were associated with chronic stress (P fdr<0.05), after adjusting for sex, age, fruit consumption, and body mass index. We identified 21 differential metabolites, predominantly enriched in metabolic pathways based on KEGG analysis. Moreover, 19 out of these metabolites were significantly correlated with at least one of the four species significantly associated with chronic stress. These metabolites may explain health effects of species associated with chronic stress. Conclusions Chronic stress in adolescents is associated with altered gut microbiota composition and metabolite profiles, providing insights into possible mechanisms underlying stress-related diseases and highlighting the importance of longitudinal studies to clarify temporal and causal relationships.
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spelling doaj-art-ee24b4cdf32d476a9a3782b6c364adb72025-08-20T03:42:23ZengBMCBMC Microbiology1471-21802025-07-0125111510.1186/s12866-025-04094-1Chronic stress is associated with altered gut microbiota profile and relevant metabolites in adolescentsLi Ying0Wang Yuhao1He Yafang2Lan Jiao3Dang Lina4Song Qinze5Yang Chenghai6Zhao Shaoxiong7Gu Yuexi8Shen Mingwang9Cai Zelin10Wang Chuangchuang11Guo Zihan12Liu Xin13Ma Lu14Zhang Lei15Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong UniversityLaboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F UniversitySpecially Life Technology Co., LtdShaanxi University of Chinese MedicineThe Second Affiliated Hospital of Shaanxi University of Chinese MedicineShaanxi University of Chinese MedicineSchool of Public Health, Xi’an Jiaotong University Health Science CenterShaanxi University of Chinese MedicineSchool of Mathematics and Statistics, Xi’an Jiaotong UniversitySchool of Public Health, Xi’an Jiaotong University Health Science CenterXi’an Jiaotong University Health Science CenterXi’an Jiaotong University Health Science CenterSchool of Public Health, Xi’an Jiaotong University Health Science CenterSchool of Public Health, Xi’an Jiaotong University Health Science CenterSchool of Public Health, Xi’an Jiaotong University Health Science CenterChina-Australia Joint Research Center for Infectious Diseases, School of Public Health, Xi’an Jiaotong University Health Science CenterAbstract Background Gut microbiota and microbiota-derived metabolites have been implicated in the regulation of stress-related diseases, yet their associations with chronic stress in adolescents remain unclear. Multi-omics studies on this topic in adolescents are still limited. This study aimed to characterize gut microbiota and metabolites in adolescents under chronic stress. Methods In this cross-sectional study, we assessed chronic stress in 124 adolescents aged 12–16 years using the Adolescent Life Events Scale and the Study Stress Scale. Participants were stratified by stress level into low (n = 42), medium (n = 41), and high stress (n = 41) groups. Fecal samples were collected from all participants for 16S rRNA gene sequencing. Subsequently, a subset of 30 adolescents with high stress and 29 low stress adolescents underwent metagenomic sequencing and untargeted metabolomics. Results Adolescents experiencing high-chronic stress showed lower alpha diversity, differential beta diversity, and a more complicated microbial network compared to those experiencing lower stress. Spearman’s rank correlation and Kruskal-Wallis test identified five genera with decreased abundances in high stress adolescents, including Faecalibacterium, Bacteroides, Akkermansia, Lachnospiraceae unclassified, and Ruminococcus (P fdr<0.05). Additionally, 12 species showed decreased abundances and 5 increased abundances, and logistic regression analysis further revealed that the relative abundances of Bifidobacterium catenulatum, Streptococcus suis, Ruminococcus sp. CAG 108, and Phascolarctobacterium faecium were associated with chronic stress (P fdr<0.05), after adjusting for sex, age, fruit consumption, and body mass index. We identified 21 differential metabolites, predominantly enriched in metabolic pathways based on KEGG analysis. Moreover, 19 out of these metabolites were significantly correlated with at least one of the four species significantly associated with chronic stress. These metabolites may explain health effects of species associated with chronic stress. Conclusions Chronic stress in adolescents is associated with altered gut microbiota composition and metabolite profiles, providing insights into possible mechanisms underlying stress-related diseases and highlighting the importance of longitudinal studies to clarify temporal and causal relationships.https://doi.org/10.1186/s12866-025-04094-1Gut microbiotaChronic stressAdolescents16S rRNAMetagenomicsMetabolism
spellingShingle Li Ying
Wang Yuhao
He Yafang
Lan Jiao
Dang Lina
Song Qinze
Yang Chenghai
Zhao Shaoxiong
Gu Yuexi
Shen Mingwang
Cai Zelin
Wang Chuangchuang
Guo Zihan
Liu Xin
Ma Lu
Zhang Lei
Chronic stress is associated with altered gut microbiota profile and relevant metabolites in adolescents
BMC Microbiology
Gut microbiota
Chronic stress
Adolescents
16S rRNA
Metagenomics
Metabolism
title Chronic stress is associated with altered gut microbiota profile and relevant metabolites in adolescents
title_full Chronic stress is associated with altered gut microbiota profile and relevant metabolites in adolescents
title_fullStr Chronic stress is associated with altered gut microbiota profile and relevant metabolites in adolescents
title_full_unstemmed Chronic stress is associated with altered gut microbiota profile and relevant metabolites in adolescents
title_short Chronic stress is associated with altered gut microbiota profile and relevant metabolites in adolescents
title_sort chronic stress is associated with altered gut microbiota profile and relevant metabolites in adolescents
topic Gut microbiota
Chronic stress
Adolescents
16S rRNA
Metagenomics
Metabolism
url https://doi.org/10.1186/s12866-025-04094-1
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