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

作者：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

来源：BMC Neurology, 2016, 16(1): 182.

DOI：10.1186/s12883-016-0703-3

• Pediatric multiple sclerosis
• Gut microbiota
• 16S rRNA
• Case-control study
• Risk factors
• Immune markers
• Disease-modifying drugs
• Microbiota-immune balance

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(+)CD25(hi)CD127(low)FoxP(3+)) 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.

• 出版日期2016-9-21