The gut microbiota in pediatric multiple sclerosis and demyelinating syndromes

Ann Clin Transl Neurol. 2021 Dec;8(12):2252-2269. doi: 10.1002/acn3.51476. Epub 2021 Dec 9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Canada
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Cohort Studies
  • Computational Biology
  • Demyelinating Autoimmune Diseases, CNS / microbiology*
  • Female
  • Gastrointestinal Microbiome*
  • Humans
  • Male
  • Multiple Sclerosis / microbiology*
  • RNA, Ribosomal, 16S


  • RNA, Ribosomal, 16S