A Cross-sectional Study of MRI Features and the Gut Microbiome in Pediatric-onset Multiple Sclerosis

Objective: To identify gut microbiome features associated with MRI lesion burden in persons with pediatric-onset multiple sclerosis (symptom onset <18 years).

Methods: A cross-sectional study involving the Canadian Paediatric Demyelinating Disease Network study participants. Gut microbiome features (alpha diversity, phylum- and genus-level taxa) were derived using 16S rRNA sequencing from stool samples. T1- and T2-weighted lesion volumes were measured on brain MRI obtained within 6 months of stool sample procurement. Associations between the gut microbiota and MRI metrics (cube-root-transformed) were assessed using standard and Lasso regression models.

Results: Thirty-four participants were included; mean ages at symptom onset and MRI were 15.1 and 19.0 years, respectively, and 79% were female. The T1- and T2-weighted lesion volumes were not significantly associated with alpha diversity (age and sex-adjusted p > 0.08). At the phylum level, high Tenericutes (relative abundance) was associated with higher T1 and T2 volumes (β coefficient = 0.25, 0.37) and high Firmicutes, Patescibacteria or Actinobacteria with lower lesion volumes (β coefficient = -0.30 to -0.07). At the genus level, high Ruminiclostridium, whereas low Coprococcus 3 and low Erysipelatoclostridium were associated with higher lesion volumes.

Interpretation: Our study characterized the gut microbiota features associated with MRI lesion burden in pediatric-onset MS, shedding light onto possible pathophysiological mechanisms.