No overall differences in the functional diversity of the gut microbiome were found in patients with pediatric-onset MS in a study using metagenomic sequencing. However, there were differences in the functional potential compared with controls at various metabolic pathways. Exposure to disease-modifying therapy (DMT) was associated with enrichment of pathways involved in promoting CNS remyelination.

A Canadian group examined the gut microbiome functional diversity and potential by metagenomic analysis of stool samples from patients ≤21 years old with pediatric-onset MS (n=20) and from controls (n=20) [1]. Participants were not allowed to be exposed to antibiotics or corticosteroids 30 days prior to sampling. MS patients were either DMT-naïve (n=8) or used interferon-beta or glatiramer acetate. Mean age of MS patients and controls was 16.1 and 15.4 years at the time of stool collection; 80% of each group was girls.

There were no statistically significant differences in functional alpha-diversity by disease or DMT status. Differential analysis of metabolic pathways revealed that MS patients exhibited numerically higher Archaea-related methanogenesis, flavin biosynthesis (producing vitamin B and flavin cofactors), viral activity, metabolism of heavy metals, and degradation of L-glutamate (which produces the short-chain fatty-acid propionate). Homolactic fermentation (lactate production, associated with anti-inflammatory effects) and bacterial carbohydrate degradation were lower compared with controls. Findings were affected by DMT exposure, with a relative enrichment of pathways involved in promoting CNS remyelination. For example, choline biosynthesis was enriched in DMT-exposed versus DMT-naïve MS patients (log-fold change 21; 95% CI 12–29; P<0.0001).

 

  1. Mirza A, et al. MSVIRTUAL2020, PS10.03.