Associations between the gut microbiota and host immune markers in pediatric multiple sclerosis and controls.

BACKGROUND

As little is known of association(s) between gut microbiota profiles and host immunological markers, we explored these in children with and without multiple sclerosis (MS).

METHODS

Children ≤18 years provided stool and blood. MS cases were within 2-years of onset. Fecal 16S rRNA gene profiles were generated on an Illumina Miseq platform. Peripheral blood mononuclear cells were isolated, and Treg (CD4CD25CD127FoxP3) frequency and CD4 T-cell intracellular cytokine production evaluated by flow cytometry. Associations between microbiota diversity, phylum-level abundances and immune markers were explored using Pearson's correlation and adjusted linear regression.

RESULTS

Twenty-four children (15 relapsing-remitting, nine controls), averaging 12.6 years were included. Seven were on a disease-modifying drug (DMD) at sample collection. Although immune markers (e.g. Th2, Th17, Tregs) did not differ between cases and controls (p > 0.05), divergent gut microbiota associations occurred; richness correlated positively with Th17 for cases (r = +0.665, p = 0.018), not controls (r = -0.644, p = 0.061). Bacteroidetes inversely associated with Th17 for cases (r = -0.719, p = 0.008), not controls (r = +0.320, p = 0.401). Fusobacteria correlated with Tregs for controls (r = +0.829, p = 0.006), not cases (r = -0.069, p = 0.808).

CONCLUSIONS

Our observations motivate further exploration to understand disruption of the microbiota-immune balance so early in the MS course.