ORIGINAL RESEARCH article
Front. Neurosci.
Sec. Gut-Brain Axis
Volume 19 - 2025 | doi: 10.3389/fnins.2025.1623165
This article is part of the Research TopicImpact of oral and gut microbiome on health and diseasesView all 22 articles
Altered Gut Microbial Networks and Metabolic Pathways in Multiple System Atrophy: A Comparative 16S rRNA Study
Provisionally accepted
- 1Cathay General Hospital, Taipei, Taiwan
- 2Department of Neurology, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan
- 3Graduate Institute of Biomedical Electronics and Bioinformatics, College of Electrical Engineering and Computer Science, National Taiwan University, Taipei, Taiwan
- 4Department of Computer Science and Information Engineering, College of Electrical Engineering and Computer Science, National Taiwan University, Taipei, Taiwan
- 5Department of Medicine, National Taiwan University Cancer Center, Taipei, Taiwan
- 6College of Medicine, National Taiwan University, Taipei, Taiwan
- 7Neurobiology and Cognitive Science Center, National Taiwan University, Taipei, Taiwan
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Introduction: The alterations in the gut microbial network in multiple system atrophy (MSA) remain poorly understood. This study aimed to identify key gut microbial interaction networks in MSA through comprehensive multimodal analyses. Methods: Demographic information and frozen fecal specimens were collected from 119 participants (MSA, n = 26; Parkinson’s disease (PD), n = 66; healthy control (HC), n = 27). Raw amplicons of the bacterial 16S rRNA V3-V4 gene region were processed using two methods: DADA2-denoising and clustering into operational taxonomic units. We conducted univariate and multivariable analyses to assess the differential abundance of bacterial genera and predicted metabolic pathways using four statistical methods: ANCOM, ANCOM-BC, ALDEx2, and MaAsLin 2. Interbacterial interactions were assessed using four correlation and two network analyses. Results: We consistently observed lower levels of Fusicatenibacter in MSA patients and lower levels of Butyricicoccus in PD patients compared with HCs (q < 0.05), both before and after adjusting for comorbidities, diet, and constipation status. The random forest classifiers effectively differentiated between MSA and PD, achieving high AUCs (0.75-0.78) in 5-fold cross-validation. A significant positive interbacterial interaction between Ruminococcus gnavus group and Erysipelatoclostridium was uniquely observed in MSA. Additionally, we identified an increase in the ARGORNPROST-PWY pathway (L-arginine degradation, q = 0.003) and a decrease in the PWY-6478 pathway (GDP-D-glycero-α-D-manno-heptose biosynthesis, q = 0.015) in MSA patients compared with HC. Conclusion: Future studies are warranted to determine whether fecal microbiome-derived signatures can serve as reliable biomarkers for MSA.
Keywords: Multiple System Atrophy, Parkinson ' s disease, gut microbiome, 16S rRNA, differential abundance analyses, correlation and network analyses
Received: 06 May 2025; Accepted: 18 Jul 2025.
Copyright: © 2025 Liu, Cheng, Li, Wang, Tseng and Kuo. 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: Ming-Che Kuo, Department of Medicine, National Taiwan University Cancer Center, Taipei, Taiwan
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