Primary progressive multiple sclerosis in a Russian cohort: relationship with gut bacterial diversity

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.

Predictive Metagenomic Analysis of Autoimmune Disease Identifies Robust Autoimmunity and Disease Specific Microbial Signatures

“…Using an expansive literature search we identified a total of 132 autoimmunity studies fulfilling our criteria ( Supplementary Figure 1 ). Following filtering based on unique data, age (2 years or older), metadata and raw file availability and sequencing depth we were able to successfully download raw (FASTQ)16S rRNA and/or shotgun metagenomics data from 42 studies, 30 with 16S rRNA sequencing data ( Hevia et al, 2014 ; Mejía-León et al, 2014 ; Stoll et al, 2014 ; Consolandi et al, 2015 ; Miyake et al, 2015 ; Chen et al, 2016a , b ; Di Paola et al, 2016 ; Dunn et al, 2016 ; Jangi et al, 2016 ; Mar et al, 2016 ; Shaw et al, 2016 ; Tejesvi et al, 2016 ; Bajer et al, 2017 ; Halfvarson et al, 2017 ; Jacob et al, 2017 ; Pascal et al, 2017 ; Goyal et al, 2018 ; Luo et al, 2018 ; Manasson et al, 2018 ; Moris et al, 2018 ; Braun et al, 2019 ; Kozhieva et al, 2019 ; Lee et al, 2019 ; Li et al, 2019 ; Ruff et al, 2019 ; Sprockett et al, 2019 ; Sun et al, 2019 ; Zegarra-Ruiz et al, 2019 ; Choileáin et al, 2020 ) and 9 studies with shotgun metagenomics data ( Lewis et al, 2015 ; Heintz-Buschart et al, 2016 ; Ananthakrishnan et al, 2017 ; Hall et al, 2017 ; Wen et al, 2017 ; Ye et al, 2018 ; Proctor et al, 2019 ; Ventura et al, 2019 ; Zhou et al, 2020 ), and 3 studies with both ( Scher et al, 2013 ; Cekanaviciute et al, 2017 ; Connors et al, 2020 ; Supplementary Table 1 and Supplementary Figure 1 ). These included studies on Inflammatory Bowel Disease (IBD, N = 14 ), Multiple Sclerosis (MS, N = 7 ), Rheumatoid Arthritis (RA, N = 5 ), Juvenile Idiopathic Arthritis (JIA, N = 3 ), Systemic Lupus Erythematosus (SLE, ...…”

Microbiome in Multiple Sclerosis: Where Are We, What We Know and Do Not Know

“…Notably, the majority of the reviewed studies referred to the Relapsing-remmitting type of MS(RRMS). A recent study addressed the differential gut microbiota profile in patients with primary progressive MS (PPMS), relatively to healthy controls [63]. As in the case of patients with RRMS, patients with PPMS have exhibited differences in a minority of a-diversity indices, whereas pattern differences have been observed at a taxonomic level [63].…”

The Core of Gut Life: Firmicutes Profile in Patients with Relapsing-Remitting Multiple Sclerosis

“…In general, the finding agrees with the established global pattern of the phylum prevalence, albeit with some exceptions [ 41 ], in the gut/fecal bacteriobiome of both healthy individuals [ 24 , 42 , 43 , 44 ] and those compromised by various disorders/diseases [ 41 , 45 , 46 ]. In this study, we did not aim at comparing the RRMS cohort with healthy individuals, yet a lower percentage of Firmicutes was often reported for healthy cohorts elsewhere [ 26 , 42 , 47 , 48 , 49 , 50 ]. As for comparing our RRMS cohort with the RRMS cohorts of other ethnicity/regions, Firmucutes was at least 20% more abundant in the studied cohort as compared with the Italian and Japanese ones [ 26 , 51 ]; the effect very likely resulted from the stark national differences in diet between these cohorts.…”