Gut Microbiome

The gut microbiome in pediatric-onset acquired demyelinating syndromes by myelin oligodendrocyte glycoprotein antibody status.

TL;DR

While alpha/beta-diversities did not differ between MOG+ and MOG- pediatric-onset acquired demyelinating syndrome participants, taxa-level differences were observed, suggesting that gut microbiome composition may differ by MOG serostatus.

Key Findings

Alpha-diversity and beta-diversity did not differ significantly between MOG-antibody-positive and MOG-antibody-negative participants with pediatric-onset acquired demyelinating syndromes.

  • Alpha-diversity was assessed using Shannon index, Margalef's index, and Chao1 measures.
  • Beta-diversity was assessed using weighted UniFrac distances.
  • All diversity comparisons yielded p > 0.3 between MOG+ and MOG- groups.
  • The study included 46 participants total: 18 MOG+ and 28 MOG-.

The relative abundance of Proteobacteria at the phylum level was significantly lower in MOG-antibody-positive participants compared to MOG-antibody-negative participants.

  • Adjusted rate ratio (aRR) for Proteobacteria in MOG+ vs. MOG-: 0.22 (95% CI: 0.07–0.69).
  • This finding survived false discovery rate correction (q = 0.03).
  • Models were adjusted for sex and age.
  • Negative binomial models were used for phylum-level taxa assessment.

The relative abundance of Escherichia/Shigella at the genus level was significantly lower in MOG-antibody-positive participants compared to MOG-antibody-negative participants.

  • Adjusted rate ratio (aRR) for Escherichia/Shigella in MOG+ vs. MOG-: 0.01 (95% CI: 0.001–0.07).
  • This finding survived false discovery rate correction (q = 0.001).
  • This was the most statistically significant taxa-level difference observed.
  • Negative binomial models adjusted for sex and age were used for genus-level assessment.

The study population consisted of 46 pediatric-onset acquired demyelinating syndrome participants enrolled in the Canadian Pediatric Demyelinating Disease Network microbiome study between 2015 and 2018.

  • 18 participants were MOG-antibody-positive and 28 were MOG-antibody-negative.
  • Mean age at stool sample collection was 14.7 years for MOG+ and 17.2 years for MOG- participants.
  • Participants were aged ≤21 years with symptom onset before age 18 years.
  • Participants had a single episode or relapsing non-MS, non-neuromyelitis optica spectrum disease attacks.
  • Serum MOG-IgG antibodies were tested within 30 days of first attack onset.

Gut microbiome profiling was conducted using 16S rRNA gene sequencing of the V4 region from stool sample-derived DNA.

  • Phylum- and genus-level taxa were assessed using negative binomial models with false discovery rate correction.
  • Rate ratios were adjusted for sex and age (aRR).
  • Both alpha-diversity (Shannon, Margalef's index, Chao1) and beta-diversity (weighted UniFrac) metrics were analyzed.

What This Means

This research examined whether children and young adults with demyelinating diseases of the central nervous system — conditions that damage the protective covering of nerve fibers — have different gut bacteria depending on whether they test positive or negative for a specific antibody called myelin oligodendrocyte glycoprotein antibody (MOG-IgG). The study included 46 participants from Canada, aged 21 or younger, who had experienced demyelinating attacks. Stool samples were analyzed to identify the types and relative amounts of bacteria present. The study found that the overall variety and balance of gut bacteria (measured as alpha- and beta-diversity) did not differ significantly between the antibody-positive and antibody-negative groups. However, at the level of specific bacterial groups, notable differences emerged: a bacterial phylum called Proteobacteria, and specifically a genus called Escherichia/Shigella within that phylum, were found at much lower levels in the antibody-positive group compared to the antibody-negative group. These differences remained statistically significant even after accounting for the possibility of false positives. This research suggests that the composition of gut bacteria may vary depending on a patient's MOG antibody status in pediatric demyelinating disease, which could potentially have implications for understanding disease mechanisms. However, the study was relatively small and cross-sectional, meaning it captured only a single point in time. The authors call for larger studies with longer follow-up periods to confirm and build upon these findings.

Have a question about this study?

Citation

Tsai W, Zhu F, Bar-Or A, Bernstein C, Bonner C, Graham M, et al.. (2026). The gut microbiome in pediatric-onset acquired demyelinating syndromes by myelin oligodendrocyte glycoprotein antibody status.. Multiple sclerosis and related disorders. https://doi.org/10.1016/j.msard.2026.107216