Gut Microbiome in Progressive Multiple Sclerosis.
Gut Microbiome in Progressive Multiple Sclerosis.
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进展型多发性硬化中的肠道微生物组
DOI：
10.1002/ana.26084
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发表时间：
2021-06
影响因子：
11.2
通讯作者：
Weiner HL
中科院分区：
文献类型：
--
作者：
Cox LM;Maghzi AH;Liu S;Tankou SK;Dhang FH;Willocq V;Song A;Wasén C;Tauhid S;Chu R;Anderson MC;De Jager PL;Polgar-Turcsanyi M;Healy BC;Glanz BI;Bakshi R;Chitnis T;Weiner HL
研究进展型多发性硬化症（MS）中的肠道微生物组以及它与临床疾病的关系。
我们对健康对照组、复发缓解型多发性硬化症（RRMS）患者和进展型多发性硬化症患者的微生物群进行了测序，并将细菌水平与疾病的临床特征相关联，包括扩展残疾状态量表（EDSS）评分、生活质量以及脑部磁共振成像（MRI）显示的病变/萎缩情况。我们用来自多发性硬化症患者的阿克曼氏菌对小鼠进行肠道菌群定植，并诱导实验性自身免疫性脑脊髓炎。
多发性硬化症患者与对照组之间微生物群的β多样性存在差异，但复发缓解型多发性硬化症与进展型多发性硬化症之间无差异，也不因疾病修正治疗而有差异。疾病状态对微生物组β多样性的影响最大，其次是体重指数（BMI）、种族和性别。在进展型和复发缓解型多发性硬化症中，我们都发现博氏梭菌、乳酸鲁氏杆菌和阿克曼氏菌增加，而韦克斯勒氏布劳特氏菌、甲酸生成多雷氏菌和丹毒丝菌科CCM减少。在进展型多发性硬化症中特有的是，我们发现肠杆菌科和梭菌g24 FCEY增加，布劳特氏菌和嗜酸乳杆菌减少。几种梭菌与较高的扩展残疾状态量表评分和疲劳评分相关。与认为多发性硬化症中阿克曼氏菌升高具有有害作用的观点相反，我们发现阿克曼氏菌与较低的残疾程度相关，表明其具有有益作用。与此一致的是，我们发现从多发性硬化症患者中分离出的阿克曼氏菌可改善实验性自身免疫性脑脊髓炎，这与产生RORγt和白细胞介素 - 17的γδ T细胞减少有关。
虽然一些微生物群的改变在复发型和进展型多发性硬化症中是相同的，但我们确定了与进展型多发性硬化症和疾病临床指标相关的独特细菌。此外，多发性硬化症中阿克曼氏菌的升高可能是多发性硬化症微生物组中的一种代偿性有益反应。
Investigate the gut microbiome in progressive multiple sclerosis (MS) and how it relates to clinical disease. We sequenced the microbiota from healthy controls, relapsing remitting MS (RRMS), and progressive MS patients and correlated the levels of bacteria with clinical features of disease, including EDSS, quality of life, and brain MRI lesions/atrophy. We colonized mice with MS-derived Akkermansia and induced experimental autoimmune encephalomyelitis. Microbiota β-diversity differed between MS patients vs. controls but did not differ between RRMS vs. progressive MS or differ based on disease modifying therapies. Disease status had the greatest effect on the microbiome β-diversity, followed by BMI, race, and sex. In both progressive and RRMS, we found increased Clostridium bolteae, Ruthenibacterium lactatiformans and Akkermansia and decreased Blautia wexlerae, Dorea formicigenerans, and Erysipelotrichaceae CCM. Unique to progressive MS, we found elevated Enterobacteriaceae and Clostridium g24 FCEY and decreased Blautia and Agathobaculum. Several Clostridium species were associated with higher EDSS and fatigue scores. Contrary to the view that elevated Akkermansia in MS has a detrimental role, we found that Akkermansia was linked to lower disability, suggesting a beneficial role. Consistent with this, we found that Akkermansia isolated from MS patients ameliorated EAE, which was linked to a reduction in RORγt+ and IL-17 producing γδ T cells. While some microbiota alterations are shared in relapsing and progressive MS, we identified unique bacteria associated with progressive MS and clinical measures of disease. Furthermore, elevated Akkermansia in MS may be a compensatory beneficial response in the MS microbiome.
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影响因子：
5.2
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通讯作者：
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