Abstract

Mounting evidence indicates that alterations in the intestinal microbiota may be associated with neurological disorders such as multiple sclerosis (MS). MS is a putative autoimmune disease of the central nervous system. However, it has not been determined whether the intestinal microbiota and host immune status are altered in Chinese patients with stable MS. In our study, 22 Chinese patients with stable MS and 33 healthy controls were enrolled for fecal microbiota analysis and host immunity evaluation. The microbial diversity and composition, bacterial co-occurrence correlations, predictive functional profiles, and microbiota-cytokine correlations between the two groups were compared. We observed that while the overall structure of the fecal microbiota did not change significantly, the abundances of several key functional bacteria, primarily Faecalibacterium, decreased remarkably. Faecalibacterium and Granulicatella could be used to distinguish between patients with MS and healthy controls with an area under the curve of 0.832. PiCRUSt analysis revealed that genes associated with fructose, mannose, and fatty acid metabolism were significantly enriched in the MS microbiota. In addition, we also observed that the levels of several pro- and anti-inflammatory cytokines and chemokines, such as IL-1ra, IL-8, IL-17, and TNF-α changed observably, and the abundances of key functional bacteria like butyrate producers correlated with the changes in the cytokine levels. Our present study indicated that altered composition of the fecal microbiota might play vital roles in the etiopathogenesis of MS by regulating host immunity, which suggests that microbiota-targeting patient-tailored early intervention techniques might serve as novel therapeutic approaches for MS.

Highlights

  • Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system with an autoimmune mechanism of development, which is one of the leading causes of disability in young adults

  • Good’s estimator of coverage was 99.33%, which indicated that the identified reads represented the majority of bacterial sequences (909 operational taxonomic unit (OTU) identified) present in the fecal microbiota

  • The alpha - and beta-diversity analyses indicated that the overall diversity of multiple sclerosis (MS)-associated fecal microbiota remained unaltered; a lower number of OTUs and phylotypes were observed in patients with MS

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Summary

Introduction

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system with an autoimmune mechanism of development, which is one of the leading causes of disability in young adults. The prevalence of MS has increased substantially in many regions since 1990, including China [2]. Several regional studies have investigated the prevalence of MS in China and have indicated increasing prevalence over time [3,4,5]. A study conducted by Cheng et al revealed that the crude MS prevalence rate was 1.39 per 100,000 individuals in Shanghai in 2004 to 2005 and the female-to-male ratio was 1.8 [6]. Another study estimated the prevalence of MS to be 3.7 and 6.7 cases per 100,000 individuals among males and females, respectively, based on hospital data for 2013 in Shandong Province [7]. There has been significant progress in the understanding of genetic and environmental factors underlying the condition.

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