Anxiety-related gut microbiota alterations in Parkinson’s disease: distinct associations compared to healthy individuals

Background and objectivesAnxiety affects 25–49% of Parkinson’s disease (PD) patients, exacerbating non-motor symptoms and significantly reducing quality of life. Growing evidence suggests that gut microbiota plays a role in anxiety, but whether its impact differs between PD and non-PD populations re...

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Main Authors: Sheng-Hsuan Lin, Ru-Jen Lin, Kai-Yu Chan, Chia-Ling Chu, Yan-Lin Chen, Shih-Chen Fu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Cellular and Infection Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2025.1594152/full
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author Sheng-Hsuan Lin
Sheng-Hsuan Lin
Sheng-Hsuan Lin
Sheng-Hsuan Lin
Ru-Jen Lin
Kai-Yu Chan
Kai-Yu Chan
Chia-Ling Chu
Yan-Lin Chen
Shih-Chen Fu
author_facet Sheng-Hsuan Lin
Sheng-Hsuan Lin
Sheng-Hsuan Lin
Sheng-Hsuan Lin
Ru-Jen Lin
Kai-Yu Chan
Kai-Yu Chan
Chia-Ling Chu
Yan-Lin Chen
Shih-Chen Fu
author_sort Sheng-Hsuan Lin
collection DOAJ
description Background and objectivesAnxiety affects 25–49% of Parkinson’s disease (PD) patients, exacerbating non-motor symptoms and significantly reducing quality of life. Growing evidence suggests that gut microbiota plays a role in anxiety, but whether its impact differs between PD and non-PD populations remains unclear. This study explores the heterogeneity of gut microbiota-associated anxiety in PD and non-PD individuals.MethodsParticipants from the NeuroGenetics Research Consortium provided clinical data, including PD status, anxiety status, and stool samples analyzed via 16S rRNA sequencing. After excluding nine participants with missing anxiety data, 322 individuals were included (193 PD, 129 non-PD). We assessed α-diversity, β-diversity, taxonomic composition, and functional pathways to compare microbial differences between anxious and non-anxious individuals within and across PD and non-PD groups.ResultsBeta diversity analysis revealed significant microbial differences between anxious and non-anxious PD patients (p = 0.043 in Bray-Curtis index) but not in the non-PD group. Escherichia-Shigella was significantly enriched in non-anxious PD patients (p = 0.011). Functional pathway analysis identified distinct metabolic alterations associated with anxiety in PD and non-PD individuals. In non-PD participants, anxiety was linked to increased activity in glycosphingolipid biosynthesis, sphingolipid metabolism, other glycan degradation, glycosphingolipid biosynthesis, and glycosaminoglycan degradation. In contrast, PD patients with anxiety exhibited enrichment in indole alkaloid biosynthesis, linoleic acid metabolism, and polyketide sugar unit biosynthesis.ConclusionGut microbiota-associated anxiety differs between PD and non-PD populations, suggesting distinct pathophysiological mechanisms. These findings underscore the potential of microbiome-targeted interventions as novel therapeutic strategies for anxiety in PD patients.
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spelling doaj-art-21ec582617954149a3e38de97d48060e2025-08-20T02:35:51ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-06-011510.3389/fcimb.2025.15941521594152Anxiety-related gut microbiota alterations in Parkinson’s disease: distinct associations compared to healthy individualsSheng-Hsuan Lin0Sheng-Hsuan Lin1Sheng-Hsuan Lin2Sheng-Hsuan Lin3Ru-Jen Lin4Kai-Yu Chan5Kai-Yu Chan6Chia-Ling Chu7Yan-Lin Chen8Shih-Chen Fu9Institute of Statistics, National Yang Ming Chiao Tung University, Hsinchu, TaiwanInstitute of Data Science and Engineering, National Yang Ming Chiao Tung University, Hsinchu, TaiwanDepartment of Applied Mathematics, National Dong Hwa University, Hualien, TaiwanDepartment of Biochemistry and Molecular Medicine, National Dong Hwa University, Hualien, TaiwanDepartment of Neurology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, TaiwanDepartment of Biochemistry and Molecular Medicine, National Dong Hwa University, Hualien, TaiwanGraduate Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung, TaiwanInstitute of Statistics, National Yang Ming Chiao Tung University, Hsinchu, TaiwanInstitute of Statistics, National Yang Ming Chiao Tung University, Hsinchu, TaiwanDepartment of Biochemistry and Molecular Medicine, National Dong Hwa University, Hualien, TaiwanBackground and objectivesAnxiety affects 25–49% of Parkinson’s disease (PD) patients, exacerbating non-motor symptoms and significantly reducing quality of life. Growing evidence suggests that gut microbiota plays a role in anxiety, but whether its impact differs between PD and non-PD populations remains unclear. This study explores the heterogeneity of gut microbiota-associated anxiety in PD and non-PD individuals.MethodsParticipants from the NeuroGenetics Research Consortium provided clinical data, including PD status, anxiety status, and stool samples analyzed via 16S rRNA sequencing. After excluding nine participants with missing anxiety data, 322 individuals were included (193 PD, 129 non-PD). We assessed α-diversity, β-diversity, taxonomic composition, and functional pathways to compare microbial differences between anxious and non-anxious individuals within and across PD and non-PD groups.ResultsBeta diversity analysis revealed significant microbial differences between anxious and non-anxious PD patients (p = 0.043 in Bray-Curtis index) but not in the non-PD group. Escherichia-Shigella was significantly enriched in non-anxious PD patients (p = 0.011). Functional pathway analysis identified distinct metabolic alterations associated with anxiety in PD and non-PD individuals. In non-PD participants, anxiety was linked to increased activity in glycosphingolipid biosynthesis, sphingolipid metabolism, other glycan degradation, glycosphingolipid biosynthesis, and glycosaminoglycan degradation. In contrast, PD patients with anxiety exhibited enrichment in indole alkaloid biosynthesis, linoleic acid metabolism, and polyketide sugar unit biosynthesis.ConclusionGut microbiota-associated anxiety differs between PD and non-PD populations, suggesting distinct pathophysiological mechanisms. These findings underscore the potential of microbiome-targeted interventions as novel therapeutic strategies for anxiety in PD patients.https://www.frontiersin.org/articles/10.3389/fcimb.2025.1594152/fullgut microbiotaParkinson’s diseaseanxietymicrobial diversityfunctional pathways16S rRNA sequencing
spellingShingle Sheng-Hsuan Lin
Sheng-Hsuan Lin
Sheng-Hsuan Lin
Sheng-Hsuan Lin
Ru-Jen Lin
Kai-Yu Chan
Kai-Yu Chan
Chia-Ling Chu
Yan-Lin Chen
Shih-Chen Fu
Anxiety-related gut microbiota alterations in Parkinson’s disease: distinct associations compared to healthy individuals
Frontiers in Cellular and Infection Microbiology
gut microbiota
Parkinson’s disease
anxiety
microbial diversity
functional pathways
16S rRNA sequencing
title Anxiety-related gut microbiota alterations in Parkinson’s disease: distinct associations compared to healthy individuals
title_full Anxiety-related gut microbiota alterations in Parkinson’s disease: distinct associations compared to healthy individuals
title_fullStr Anxiety-related gut microbiota alterations in Parkinson’s disease: distinct associations compared to healthy individuals
title_full_unstemmed Anxiety-related gut microbiota alterations in Parkinson’s disease: distinct associations compared to healthy individuals
title_short Anxiety-related gut microbiota alterations in Parkinson’s disease: distinct associations compared to healthy individuals
title_sort anxiety related gut microbiota alterations in parkinson s disease distinct associations compared to healthy individuals
topic gut microbiota
Parkinson’s disease
anxiety
microbial diversity
functional pathways
16S rRNA sequencing
url https://www.frontiersin.org/articles/10.3389/fcimb.2025.1594152/full
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