Woh Pei Yee, Chen Yehao, Kumpitsch Christina, Mohammadzadeh Rokhsareh, Schmidt Laura, Moissl-Eichinger Christine
Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Hong Kong, China.
Research Institute for Future Food (RiFood), The Hong Kong Polytechnic University, Hong Kong, China.
Microbiol Spectr. 2025 Apr;13(4):e0218324. doi: 10.1128/spectrum.02183-24. Epub 2025 Feb 25.
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 species. Most MS patients were female (80/115), aged 25-72 years (median: 44.5), and 70% were undergoing treatment, including dimethyl fumarate ( = 21), fingolimod ( = 20), glatiramer acetate ( = 14), interferon ( = 18), natalizumab ( = 6), or ocrelizumab/rituximab ( = 1). We found no significant differences in overall archaeome profiles between MS patients and controls. However, treated MS patients exhibited higher abundances of and sp900766745 compared to untreated patients. Notably, 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 and 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.
肠道古菌微生物组（古菌组）在健康和疾病中的作用仍知之甚少。产甲烷古菌与多发性硬化症（MS）有关，但先前的研究受限于样本量小和方法不一致。为了解决这个问题，我们使用国际多发性硬化症微生物组研究的宏基因组数据重新评估了产甲烷古菌与MS之间的关联。我们分析了来自布宜诺斯艾利斯（27.8%）、爱丁堡（33.9%）、纽约（10.4%）和旧金山（27.8%）的115名MS患者和115名健康家庭对照的肠道微生物组概况。使用kraken2/bracken和一个经过整理的分析数据库对宏基因组序列进行分类学分类，以检测古菌，特别是[具体物种]。大多数MS患者为女性（80/115），年龄在25 - 72岁之间（中位数：44.5岁），70%正在接受治疗，包括富马酸二甲酯（n = 21）、芬戈莫德（n = 20）、醋酸格拉替雷（n = 14）、干扰素（n = 18）、那他珠单抗（n = 6）或奥瑞珠单抗/利妥昔单抗（n = 1）。我们发现MS患者和对照组之间的整体古菌组概况没有显著差异。然而，与未治疗的患者相比，接受治疗的MS患者中[具体物种1]和[物种名称]sp900766745的丰度更高。值得注意的是，在接受治疗的患者中，[物种名称]sp900766745的丰度与较低的疾病严重程度评分相关。我们的结果表明，肠道产甲烷菌与MS的发病或进展没有直接关联，但可能反映了治疗期间微生物组的健康状况。这些发现突出了[具体物种1]和[物种名称]sp900766745在调节治疗结果中的潜在作用，有必要进一步研究它们与肠道微生物组功能和MS管理的相关性。
重要性
多发性硬化症（MS）是一种影响中枢神经系统的慢性神经炎症性疾病，全球约有280万人被诊断出患有此病，主要是20 - 30岁的年轻人。虽然最近的研究集中在MS微生物组中的细菌变化，但肠道古菌的作用研究较少。先前的研究表明产甲烷古菌与MS疾病状态之间可能存在联系，但这些发现仍无定论。我们的研究通过调查MS患者的肠道古菌组成并检查其对治疗的反应如何变化来填补这一空白。通过关注产甲烷菌，我们旨在揭示它们在MS中的作用的新见解，可能揭示新的生物标志物或治疗靶点。这项研究对于加强我们对肠道微生物组对MS的影响的理解和改善患者管理至关重要。
