Dysbiosis in the Gut Microbiota of Patients with Multiple Sclerosis, with a Striking Depletion of Species Belonging to Clostridia XIVa and IV Clusters.
Dysbiosis in the Gut Microbiota of Patients with Multiple Sclerosis, with a Striking Depletion of Species Belonging to Clostridia XIVa and IV Clusters.
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DOI：
10.1371/journal.pone.0137429
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Yamamura T
中科院分区：
文献类型：
--
作者：
Miyake S;Kim S;Suda W;Oshima K;Nakamura M;Matsuoka T;Chihara N;Tomita A;Sato W;Kim SW;Morita H;Hattori M;Yamamura T
多发性硬化症（MS）是一种影响大脑和脊髓的自身免疫性疾病，其发病机制仍知之甚少。MS患者通常表现为反复发作的神经功能障碍，如失明、轻瘫和感觉障碍。对实验性自身免疫性脑脊髓炎（EAE）动物模型的研究已经产生了许多可检验的假设，包括改变的肠道微生物群在MS发展中的假设作用。为了研究MS患者的肠道微生物群是否改变，我们比较了20名复发缓解型（RR）MS（MS 20）日本患者和40名健康日本受试者（HC 40）的肠道微生物群。以及另外18名健康受试者（HC 18）。所有HC 18受试者在数月内重复提供粪便样本（共158份样本）。通过使用高通量培养物独立的焦磷酸测序方法分析细菌16 S核糖体RNA（rRNA）基因，提供了MS患者肠道微生物群结构中度失调的证据。此外，我们发现21个物种在MS 20和HC 40样品之间的相对丰度存在显着差异。在比较MS样品与158个纵向HC 18样品时，发现大多数物种的差异具有可重复性。这些分类群主要由属于梭菌属簇XIVa和IV的梭菌属种和拟杆菌属种组成。系统发育树分析显示，在MS患者的肠道微生物群中显著减少的梭菌物种与能够诱导结肠调节性T细胞（Treg）的其他孢子形成梭菌物种均不重叠，这可以预防自身免疫和过敏;这表明许多与MS相关的梭菌物种可能与广泛与自身免疫性疾病相关的梭菌物种不同。纠正生态失调和改变肠道微生物群可能值得考虑作为预防和治疗MS的潜在策略。
The pathogenesis of multiple sclerosis (MS), an autoimmune disease affecting the brain and spinal cord, remains poorly understood. Patients with MS typically present with recurrent episodes of neurological dysfunctions such as blindness, paresis, and sensory disturbances. Studies on experimental autoimmune encephalomyelitis (EAE) animal models have led to a number of testable hypotheses including a hypothetical role of altered gut microbiota in the development of MS. To investigate whether gut microbiota in patients with MS is altered, we compared the gut microbiota of 20 Japanese patients with relapsing-remitting (RR) MS (MS20) with that of 40 healthy Japanese subjects (HC40) and an additional 18 healthy subjects (HC18). All the HC18 subjects repeatedly provided fecal samples over the course of months (158 samples in total). Analysis of the bacterial 16S ribosomal RNA (rRNA) gene by using a high-throughput culture-independent pyrosequencing method provided evidence of a moderate dysbiosis in the structure of gut microbiota in patients with MS. Furthermore, we found 21 species that showed significant differences in relative abundance between the MS20 and HC40 samples. On comparing MS samples to the 158 longitudinal HC18 samples, the differences were found to be reproducibly significant for most of the species. These taxa comprised primarily of clostridial species belonging to Clostridia clusters XIVa and IV and Bacteroidetes. The phylogenetic tree analysis revealed that none of the clostridial species that were significantly reduced in the gut microbiota of patients with MS overlapped with other spore-forming clostridial species capable of inducing colonic regulatory T cells (Treg), which prevent autoimmunity and allergies; this suggests that many of the clostridial species associated with MS might be distinct from those broadly associated with autoimmune conditions. Correcting the dysbiosis and altered gut microbiota might deserve consideration as a potential strategy for the prevention and treatment of MS.