Reevaluation of the gastrointestinal methanogenic archaeome in multiple sclerosis and its association with treatment

ABSTRACT The role of the gut archaeal microbiome (archaeome) in health and disease remains poorly understood. Methanogenic archaea have been linked to multiple sclerosis (MS), but prior studies were limited by small cohorts and inconsistent methodologies. To address this, we re-evaluated the associa...

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Main Authors: Pei Yee Woh, Yehao Chen, Christina Kumpitsch, Rokhsareh Mohammadzadeh, Laura Schmidt, Christine Moissl-Eichinger
Format: Article
Language:English
Published: American Society for Microbiology 2025-04-01
Series:Microbiology Spectrum
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Online Access:https://journals.asm.org/doi/10.1128/spectrum.02183-24
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author Pei Yee Woh
Yehao Chen
Christina Kumpitsch
Rokhsareh Mohammadzadeh
Laura Schmidt
Christine Moissl-Eichinger
author_facet Pei Yee Woh
Yehao Chen
Christina Kumpitsch
Rokhsareh Mohammadzadeh
Laura Schmidt
Christine Moissl-Eichinger
author_sort Pei Yee Woh
collection DOAJ
description ABSTRACT The role of the gut archaeal microbiome (archaeome) in health and disease remains poorly understood. Methanogenic archaea have been linked to multiple sclerosis (MS), but prior studies were limited by small cohorts and inconsistent methodologies. To address this, we re-evaluated the association between methanogenic archaea and MS using metagenomic data from the International Multiple Sclerosis Microbiome Study. We analyzed gut microbiome profiles from 115 MS patients and 115 healthy household controls across Buenos Aires (27.8%), Edinburgh (33.9%), New York (10.4%), and San Francisco (27.8%). Metagenomic sequences were taxonomically classified using kraken2/bracken and a curated profiling database to detect archaea, specifically Methanobrevibacter species. Most MS patients were female (80/115), aged 25–72 years (median: 44.5), and 70% were undergoing treatment, including dimethyl fumarate (n = 21), fingolimod (n = 20), glatiramer acetate (n = 14), interferon (n = 18), natalizumab (n = 6), or ocrelizumab/rituximab (n = 1). We found no significant differences in overall archaeome profiles between MS patients and controls. However, treated MS patients exhibited higher abundances of Methanobrevibacter smithii and M. sp900766745 compared to untreated patients. Notably, M. sp900766745 abundance correlated with lower disease severity scores in treated patients. Our results suggest that gut methanogens are not directly associated with MS onset or progression but may reflect microbiome health during treatment. These findings highlight potential roles for M. smithii and M. sp900766745 in modulating treatment outcomes, warranting further investigation into their relevance to gut microbiome function and MS management.IMPORTANCEMultiple sclerosis (MS) is a chronic neuroinflammatory disease affecting the central nervous system, with approximately 2.8 million people diagnosed worldwide, mainly young adults aged 20–30 years. While recent studies have focused on bacterial changes in the MS microbiome, the role of gut archaea has been less explored. Previous research suggested a potential link between methanogenic archaea and MS disease status, but these findings remained inconclusive. Our study addresses this gap by investigating the gut archaeal composition in MS patients and examining how it changes in response to treatment. By focusing on methanogens, we aim to uncover novel insights into their role in MS, potentially revealing new biomarkers or therapeutic targets. This research is crucial for enhancing our understanding of the gut microbiome’s impact on MS and improving patient management.
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spelling doaj-art-779db14a264544be96daf65ff30a3bd82025-08-20T01:53:57ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972025-04-0113410.1128/spectrum.02183-24Reevaluation of the gastrointestinal methanogenic archaeome in multiple sclerosis and its association with treatmentPei Yee Woh0Yehao Chen1Christina Kumpitsch2Rokhsareh Mohammadzadeh3Laura Schmidt4Christine Moissl-Eichinger5Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Hong Kong, ChinaDepartment of Food Science and Nutrition, The Hong Kong Polytechnic University, Hong Kong, ChinaDiagnostic and Research Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, AustriaDiagnostic and Research Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, AustriaDiagnostic and Research Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, AustriaDiagnostic and Research Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, AustriaABSTRACT The role of the gut archaeal microbiome (archaeome) in health and disease remains poorly understood. Methanogenic archaea have been linked to multiple sclerosis (MS), but prior studies were limited by small cohorts and inconsistent methodologies. To address this, we re-evaluated the association between methanogenic archaea and MS using metagenomic data from the International Multiple Sclerosis Microbiome Study. We analyzed gut microbiome profiles from 115 MS patients and 115 healthy household controls across Buenos Aires (27.8%), Edinburgh (33.9%), New York (10.4%), and San Francisco (27.8%). Metagenomic sequences were taxonomically classified using kraken2/bracken and a curated profiling database to detect archaea, specifically Methanobrevibacter species. Most MS patients were female (80/115), aged 25–72 years (median: 44.5), and 70% were undergoing treatment, including dimethyl fumarate (n = 21), fingolimod (n = 20), glatiramer acetate (n = 14), interferon (n = 18), natalizumab (n = 6), or ocrelizumab/rituximab (n = 1). We found no significant differences in overall archaeome profiles between MS patients and controls. However, treated MS patients exhibited higher abundances of Methanobrevibacter smithii and M. sp900766745 compared to untreated patients. Notably, M. sp900766745 abundance correlated with lower disease severity scores in treated patients. Our results suggest that gut methanogens are not directly associated with MS onset or progression but may reflect microbiome health during treatment. These findings highlight potential roles for M. smithii and M. sp900766745 in modulating treatment outcomes, warranting further investigation into their relevance to gut microbiome function and MS management.IMPORTANCEMultiple sclerosis (MS) is a chronic neuroinflammatory disease affecting the central nervous system, with approximately 2.8 million people diagnosed worldwide, mainly young adults aged 20–30 years. While recent studies have focused on bacterial changes in the MS microbiome, the role of gut archaea has been less explored. Previous research suggested a potential link between methanogenic archaea and MS disease status, but these findings remained inconclusive. Our study addresses this gap by investigating the gut archaeal composition in MS patients and examining how it changes in response to treatment. By focusing on methanogens, we aim to uncover novel insights into their role in MS, potentially revealing new biomarkers or therapeutic targets. This research is crucial for enhancing our understanding of the gut microbiome’s impact on MS and improving patient management.https://journals.asm.org/doi/10.1128/spectrum.02183-24human microbiomegut microbiomearchaeaarchaeomemultiple sclerosis
spellingShingle Pei Yee Woh
Yehao Chen
Christina Kumpitsch
Rokhsareh Mohammadzadeh
Laura Schmidt
Christine Moissl-Eichinger
Reevaluation of the gastrointestinal methanogenic archaeome in multiple sclerosis and its association with treatment
Microbiology Spectrum
human microbiome
gut microbiome
archaea
archaeome
multiple sclerosis
title Reevaluation of the gastrointestinal methanogenic archaeome in multiple sclerosis and its association with treatment
title_full Reevaluation of the gastrointestinal methanogenic archaeome in multiple sclerosis and its association with treatment
title_fullStr Reevaluation of the gastrointestinal methanogenic archaeome in multiple sclerosis and its association with treatment
title_full_unstemmed Reevaluation of the gastrointestinal methanogenic archaeome in multiple sclerosis and its association with treatment
title_short Reevaluation of the gastrointestinal methanogenic archaeome in multiple sclerosis and its association with treatment
title_sort reevaluation of the gastrointestinal methanogenic archaeome in multiple sclerosis and its association with treatment
topic human microbiome
gut microbiome
archaea
archaeome
multiple sclerosis
url https://journals.asm.org/doi/10.1128/spectrum.02183-24
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