Abstract

BackgroundGut microbiota has been increasingly acknowledged to shape significantly human health, contributing to various autoimmune diseases, both intestinal and non-intestinal, including multiple sclerosis (MS). Gut microbiota studies in patients with relapsing remitting MS strongly suggested its possible role in immunoregulation; however, the profile and potential of gut microbiota involvement in patients with primary progressive MS (PPMS) patients has received much less attention due to the rarity of this disease form. We compared the composition and structure of faecal bacterial assemblage using Illumina MiSeq sequencing of V3-V4 hypervariable region of 16S rRNA genes amplicons in patients with primary progressive MS and in the healthy controls.ResultsOver all samples 12 bacterial phyla were identified, containing 21 classes, 25 orders, 54 families, 174 genera and 1256 operational taxonomic units (OTUs). The Firmicutes phylum was found to be ultimately dominating both in OTUs richness (68% of the total bacterial OTU number) and in abundance (71% of the total number of sequence reads), followed by Bacteroidetes (12 and 16%, resp.) and Actinobacteria (7 and 6%, resp.). Summarily in all samples the number of dominant OTUs, i.e. OTUs with ≥1% relative abundance, was 13, representing much less taxonomic richness (three phyla, three classes, four orders, six families and twelve genera) as compared to the total list of identified OTUs and accounting for 30% of the sequence reads number in the healthy cohort and for 23% in the PPMS cohort. Human faecal bacterial diversity profiles were found to differ between PPMS and healthy cohorts at different taxonomic levels in minor or rare taxa. Marked PPMS-associated increase was found in the relative abundance of two dominant OTUs (Gemmiger sp. and an unclassified Ruminococcaceae). The MS-related differences were also found at the level of minor and rare OTUs (101 OTUs). These changes in OTUs’ abundance translated into increased bacterial assemblage diversity in patients.ConclusionThe findings are important for constructing a more detailed global picture of the primary progressive MS-associated gut microbiota, contributing to better understanding of the disease pathogenesis.

Highlights

  • Gut microbiota has been increasingly acknowledged to shape significantly human health, contributing to various autoimmune diseases, both intestinal and non-intestinal, including multiple sclerosis (MS)

  • After quality filtering and chimera removal a total of 1256 different operational taxonomic unit (OTU) were identified at 97% sequence identity level, of which the overwhelming majority (1252) was Bacteria, the rest four representing the Euryarchaeota phylum of the Archaea domain

  • The overwhelming majority of OTUs in the faecal bacterial assemblages were ascribed to the Firmicutes phylum

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Summary

Introduction

Gut microbiota has been increasingly acknowledged to shape significantly human health, contributing to various autoimmune diseases, both intestinal and non-intestinal, including multiple sclerosis (MS). Gut microbiota has been increasingly and explicitly acknowledged to shape significantly human health, in particular contributing to various autoimmune diseases, both intestinal and non-intestinal, such as multiple sclerosis, type-1 diabetes, systemic lupus erythematosus, psoriasis, schizophrenia, and some other disorders [1, 2]. Some recently reported results are quite suggestive: for instance, transplantation of gut microbiota from multiple sclerosis patients was found to enable spontaneous autoimmune encephalomyelitis in mice [7], and new hypotheses, based on microbes’ involvement, have been proposed as causes for a range of chronic inflammatory diseases, including MS [8]. The development of such strategies needs a more detailed picture of microbiome specifics in the MS-afflicted cohorts in different regions of the world and an improved understanding of the interactions between the microbiota and the host [10]

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