Dataset Information

The Gut Microbiota and Pediatric Multiple Sclerosis: Recent Findings.

ABSTRACT: Pediatric multiple sclerosis (MS) is a chronic, life-long neurological condition associated with inflammation and degeneration in the brain and spinal cord. Fortunately, < 5% of people with MS have their onset in childhood years. However, studying these very-early-onset cases of MS offers key advantages. In particular, with fewer years lived, children have had a limited range of exposures, potentially enhancing our ability to identify what might cause MS. Further, as the actual timing of the biological MS onset is unknown, the possibility to study these children much closer to the real onset of disease is far greater than in the typical adult with MS. Whether MS (in children or adults) can be prevented is unknown and the available drugs are only modestly effective in modifying the disease course and are not without risk. Emerging evidence is providing insight into the gut microbiota's potential role in triggering and shaping neurological conditions such as MS. The limited number of studies in humans with MS and absence of prior work in pediatric MS motivated the following 3 fundamental questions, addressed in 2 cross-sectional and 1 longitudinal investigation in children with and without MS: 1) Does the gut microbiota composition differ between children with and without MS? 2) Is there an association between the gut microbiota and host immune markers in children with and without MS? 3) Is the gut microbiota associated with the future risk of a MS relapse?

SUBMITTER: Tremlett H

PROVIDER: S-EPMC5794692 | biostudies-other | 2018 Jan

REPOSITORIES: biostudies-other

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The Gut Microbiota and Pediatric Multiple Sclerosis: Recent Findings.

Tremlett Helen H Waubant Emmanuelle E

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 20180101 1

Pediatric multiple sclerosis (MS) is a chronic, life-long neurological condition associated with inflammation and degeneration in the brain and spinal cord. Fortunately, < 5% of people with MS have their onset in childhood years. However, studying these very-early-onset cases of MS offers key advantages. In particular, with fewer years lived, children have had a limited range of exposures, potentially enhancing our ability to identify what might cause MS. Further, as the actual timing of the bio ...[more]

PMID: 28940049

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Project description:ObjectiveTo examine the gut microbiota in individuals with and without pediatric-onset multiple sclerosis (MS).MethodsWe compared stool-derived microbiota of Canadian Pediatric Demyelinating Disease Network study participants ≤21 years old, with MS (disease-modifying drug [DMD] exposed and naïve) or monophasic acquired demyelinating syndrome [monoADS] (symptom onset <18 years), and unaffected controls. All were ≥30 days without antibiotics or corticosteroids. V4 region 16S RNA gene-derived amplicon sequence variants (Illumina MiSeq) were assessed using negative binomial regression and network analyses; rate ratios were age- and sex-adjusted (aRR).ResultsThirty-two MS, 41 monoADS (symptom onset [mean] = 14.0 and 6.9 years) and 36 control participants were included; 75%/56%/58% were female, with mean ages at stool sample = 16.5/13.8/15.1 years, respectively. Nine MS cases (28%) were DMD-naïve. Although microbiota diversity (alpha, beta) did not differ between participants (p > 0.1), taxa-level and gut community networks did. MS (vs. monoADS) exhibited > fourfold higher relative abundance of the superphylum Patescibacteria (aRR = 4.2;95%CI:1.6-11.2, p = 0.004, Q = 0.01), and lower abundances of short-chain fatty acid (SCFA)-producing Lachnospiraceae (Anaerosporobacter) and Ruminococcaceae (p, Q < 0.05). DMD-naïve MS cases were depleted for Clostridiales vadin-BB60 (unnamed species) versus either DMD-exposed, controls (p, Q < 0.01), or monoADS (p = 0.001, Q = 0.06) and exhibited altered community connectedness (p < 10-9 Kruskal-Wallis), with SCFA-producing taxa underrepresented. Consistent taxa-level findings from an independent US Network of Pediatric MS Centers case/control (n = 51/42) cohort included >eightfold higher abundance for Candidatus Stoquefichus and Tyzzerella (aRR = 8.8-12.8, p < 0.05) in MS cases and 72%-80% lower abundance of SCFA-producing Ruminococcaceae-NK4A214 (aRR = 0.38-0.2, p ≤ 0.01).InterpretationGut microbiota community structure, function and connectivity, and not just individual taxa, are of likely importance in MS.

Project description:BackgroundMultiple sclerosis is a chronic immune-mediated disease of the brain and spinal cord resulting in physical and cognitive impairment in young adults. It is hypothesized that a disrupted bacterial and viral gut microbiota is a part of the pathogenesis mediating disease impact through an altered gut microbiota-brain axis. The aim of this study is to explore the characteristics of gut microbiota in multiple sclerosis and to associate it with disease variables, as the etiology of the disease remains only partially known.MethodsHere, in a case-control setting involving 148 Danish cases with multiple sclerosis and 148 matched healthy control subjects, we performed shotgun sequencing of fecal microbial DNA and associated bacterial and viral microbiota findings with plasma cytokines, blood cell gene expression profiles, and disease activity.ResultsWe found 61 bacterial species that were differentially abundant when comparing all multiple sclerosis cases with healthy controls, among which 31 species were enriched in cases. A cluster of inflammation markers composed of blood leukocytes, CRP, and blood cell gene expression of IL17A and IL6 was positively associated with a cluster of multiple sclerosis-related species. Bacterial species that were more abundant in cases with disease-active treatment-naïve multiple sclerosis were positively linked to a group of plasma cytokines including IL-22, IL-17A, IFN-β, IL-33, and TNF-α. The bacterial species richness of treatment-naïve multiple sclerosis cases was associated with number of relapses over a follow-up period of 2 years. However, in non-disease-active cases, we identified two bacterial species, Faecalibacterium prausnitzii and Gordonibacter urolithinfaciens, whose absolute abundance was enriched. These bacteria are known to produce anti-inflammatory metabolites including butyrate and urolithin. In addition, cases with multiple sclerosis had a higher viral species diversity and a higher abundance of Caudovirales bacteriophages.ConclusionsConsiderable aberrations are present in the gut microbiota of patients with multiple sclerosis that are directly associated with blood biomarkers of inflammation, and in treatment-naïve cases bacterial richness is positively associated with disease activity. Yet, the finding of two symbiotic bacterial species in non-disease-active cases that produce favorable immune-modulating compounds provides a rationale for testing these bacteria as adjunct therapeutics in future clinical trials.

Dataset Information

The Gut Microbiota and Pediatric Multiple Sclerosis: Recent Findings.

Publications

The Gut Microbiota and Pediatric Multiple Sclerosis: Recent Findings.

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