title: Associations between the gut microbiota and host immune markers in pediatric multiple sclerosis and controls.
abstract: 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.
authors.affiliation: Faculty of Medicine (Neurology), University of British Columbia, Room S178, 2211 Wesbrook Mall, Vancouver, BC, V6T 2B5, Canada. helen.tremlett@ubc.ca.
authors.forename: Helen
authors.initials: H
authors.lastname: Tremlett
authors.affiliation: University of California, San Francisco, CA, USA.
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Fadrosh
authors.affiliation: University of California, San Francisco, CA, USA.
authors.forename: Ali A
authors.initials: AA
authors.lastname: Faruqi
authors.affiliation: University of California, San Francisco, CA, USA.
authors.forename: Janace
authors.initials: J
authors.lastname: Hart
authors.affiliation: University of Utah, Salt Lake City, UT, USA.
authors.forename: Shelly
authors.initials: S
authors.lastname: Roalstad
authors.affiliation: University of California, San Francisco, CA, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Graves
authors.affiliation: University of California, San Francisco, CA, USA.
authors.forename: Collin M
authors.initials: CM
authors.lastname: Spencer
authors.affiliation: University of California, San Francisco, CA, USA.
authors.forename: Susan V
authors.initials: SV
authors.lastname: Lynch
authors.affiliation: University of California, San Francisco, CA, USA.
authors.forename: Scott S
authors.initials: SS
authors.lastname: Zamvil
authors.affiliation: University of California, San Francisco, CA, USA.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Waubant
keywords: 16S rRNA; Case–control study; Disease-modifying drugs; Gut microbiota; Immune markers; Microbiota-immune balance; Pediatric multiple sclerosis; Risk factors