Open AccessThe gut microbiota in pediatric multiple sclerosis and demyelinating syndromes
Author(s) -
Tremlett Helen,
Zhu Feng,
Arnold Douglas,
BarOr Amit,
Bernstein Charles N.,
Bonner Christine,
Forbes Jessica D.,
Graham Morag,
Hart Janace,
Knox Natalie C.,
Marrie Ruth Ann,
Mirza Ali I.,
O’Mahony Julia,
Van Domselaar Gary,
Yeh E. Ann,
Zhao Yinshan,
Banwell Brenda,
Waubant Emmanuelle
Publication year - 2021
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.51476
Subject(s) - lachnospiraceae , multiple sclerosis , medicine , amplicon sequencing , clinically isolated syndrome , gastroenterology , microbiome , gut flora , immunology , biology , bioinformatics , 16s ribosomal rna , genetics , gene , firmicutes
Objective To examine the gut microbiota in individuals with and without pediatric‐onset multiple sclerosis (MS). Methods We 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). Results Thirty‐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). Interpretation Gut microbiota community structure, function and connectivity, and not just individual taxa, are of likely importance in MS.