Associations between the gut microbiota and host immune markers in pediatric multiple sclerosis and controls Tremlett, Helen; Fadrosh, Douglas W; Faruqi, Ali A; Hart, Janace; Roalstad, Shelly; Graves, Jennifer; Spencer, Collin M; Lynch, Susan V; Zamvil, Scott S; Waubant, Emmanuelle
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 (CD4+CD25hiCD127lowFoxP3+) 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.
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