Journal Article

The gut microbiota in pediatric multiple sclerosis and demyelinating syndromes

Yeh, E. Ann, Bar‐Or, Amit, Marrie, Ruth Ann, Banwell, Brenda, Zhu, Feng, Mirza, Ali I., Forbes, Jessica D., O’Mahony, Julia, Van Domselaar, Gary, Tremlett, Helen, Knox, Natalie C., Zhao, Yinshan, Waubant, Emmanuelle, Arnold, Douglas, Graham, Morag, Bernstein, Charles N., Hart, Janace, Bonner, Christine

2021

Overview

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.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
• Subject: Adolescent / Age / Antibiotics / Body mass index / Canada / Case-Control Studies / Child / Child, Preschool / Chronic illnesses / Cohort Studies / Computational Biology / Demyelinating Autoimmune Diseases, CNS - microbiology / Dietary supplements / Disease / Female / Females / Gastrointestinal Microbiome / Gut microbiota / Humans / Inflammatory bowel disease / Laboratories / Male / Metabolism / Microbiota / Multiple sclerosis / Multiple Sclerosis - microbiology / Pediatrics / Proteins / RNA, Ribosomal, 16S / Values