Sci Rep：肠道细菌或和多发性硬化症发病相关

Sci Rep：肠道细菌或和多发性硬化症发病相关
2016/7/1 3:44:02Scientific Repor 世界医疗科技资讯

     如果被问及有害的肠道细菌会引发什么问题，大多数人或许都认为有害肠道菌群会引发消化道问题，比如便秘、胃胀气或腹泻；但近日科学家们发现，有害细菌，或有益细菌水平不够或许和多发性硬化症发生直接相关，相关研究发表于Scientific Reports杂志上。

     Ashutosh Mangalam博士表示，人类机体肠道中携带着数万亿个细菌，俗称为肠道微生物组，近年来多项研究表明，肠道菌群在改善并维持人体健康上扮演着重要作用。肠道细菌往往机体健康息息相关，为此研究人员就想知道是否肠道菌群和慢性自身免疫性疾病直接相关，比如多发性硬化症等，同时研究者还想知道是否自身免疫性疾病患者机体的肠道微生物组不同于健康个体的肠道微生物组。

     研究者表示，实际上多发性硬化症患者有着和健康个体不同的肠道微生物组，尽管这是一项初步研究，但相关数据表明，多发性患者机体中有益菌群的水平较低，比如那些从健康食物(黄豆、亚麻)中获取效益的有益菌群。

     研究者Mangalam和来自梅奥诊所的的研究者对来自多发性硬化症患者的粪便样本进行微生物组分析，同时以健康个体作为对照；结果表明，相比对照健康个体而言，多发性硬化症患者机体中特定菌群的水平降低或升高了；后期研究中研究者表示，他们还将通过对大量研究对象进行更为深入的研究来证实本文中的研究发现。

     原文阅读

     Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls

     Jun Chen, Nicholas Chia, Krishna R. Kalari, Janet Z. Yao, Martina Novotna, M. Mateo Paz Soldan, David H. Luckey, Eric V. Marietta, Patricio R. Jeraldo, Xianfeng Chen, Brian G. Weinshenker, Moses Rodriguez, Orhun H. Kantarci, Heidi Nelson, Joseph A. Murray & Ashutosh K. Mangalam

     AbstractMultiple sclerosis (MS) is an immune-mediated disease, the etiology of which involves both genetic and environmental factors. The exact nature of the environmental factors responsible for predisposition to MS remains elusive; however, it’s hypothesized that gastrointestinal microbiota might play an important role in pathogenesis of MS. Therefore, this study was designed to investigate whether gut microbiota are altered in MS by comparing the fecal microbiota in relapsing remitting MS (RRMS) (n?=?31) patients to that of age- and gender-matched healthy controls (n?=?36). Phylotype profiles of the gut microbial populations were generated using hypervariable tag sequencing of the V3–V5 region of the 16S ribosomal RNA gene. Detailed fecal microbiome analyses revealed that MS patients had distinct microbial community profile compared to healthy controls. We observed an increased abundance of Psuedomonas, Mycoplana, Haemophilus, Blautia, and Dorea genera in MS patients, whereas control group showed increased abundance of Parabacteroides, Adlercreutzia and Prevotella genera. Thus our study is consistent with the hypothesis that MS patients have gut microbial dysbiosis and further study is needed to better understand their role in the etiopathogenesis of MS.

     Introduction

     Multiple sclerosis (MS) is a pro-inflammatory demyelinating disease of the central nervous system (CNS)¹. Most MS patients (~85%) present with a relapsing-remitting MS (RRMS) disease course characterized by clearly defined attacks or relapses, followed by a variable degree of recovery. The etiology of MS is complex and poorly understood. Both genetic and environmental factors play a role^2,3, and recent evidence suggests that gut microbiota is one of the key environmental factors. According to the “hygiene hypothesis”, reduced exposure to infections in childhood may increase the risk of allergic and autoimmune diseases^4,5. Supporting this argument, Western societies report an increased incidence of diseases with an autoimmune/allergic component, including MS. Increased constipation and fecal incontinence⁶ and increased gut permeability⁷ in MS patients, and increased occurrence of inflammatory bowel diseases (IBD) in MS patients and their families^8,9, suggest an important gut–CNS connection. Interestingly, gut bacteria can also influence the blood brain barrier integrity¹⁰. These studies implicate that gut microbiota may potentially be operational in predisposition to or modification of the disease course of MS. Therefore we hypothesized that RRMS patients have gut microbial dysbiosis compared to healthy controls.

     To test our hypothesis, we analyze the fecal microbiota composition in patients in the active or remission phases of RRMS and compare it to that of healthy controls. We show that RRMS patients have a distinct microbial community profile compared to healthy controls.

     Results

     Gut Microbiota of RRMS Patients Differs from Healthy controlsTo determine if MS is associated with a change in microbial diversity, fecal samples from 31 RRMS patients were sequenced (Table 1 and Fig. 1) and analyzed using IM_TORNEDO¹¹. The median sequencing length obtained was 58,272 bases (range 2,658–894,587). After removing singletons, these sequences were clustered into OTUs based on 97% sequence similarity. Taxonomic classification revealed a typical Western diet diversity profile comprising Firmicutes (58.6%), Bacteroidetes (40.4%), Proteobacteria (0.7%), Actinobacteria (0.1%), and a tail of rare bacterial phyla (0.2%) (Supplemental Figure S1). The overall species richness of the gut microbiota of the RRMS patients was not significantly different from that of the healthy controls (P?=?0.73 for observed OTU number, Supplemental Figure S2). However, when RRMS patients were divided into patients with active disease and those in remission, there was a trend towards lower species richness in patients with active disease compared to healthy controls (P?=?0.1). The microbiota in patients in the remission phase exhibited species richness similar to the healthy controls (Fig. 2A). The Shannon diversity index, which considers both the species richness and evenness, also identified a similar decreasing trend in species richness for patients in the active disease state (P?=?0.2, Fig. 2B).

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