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

Greg Aaen, Anita Belman, Leslie Benson, Charlie Casper, Tanuja Chitnis, Mark Gorman, Yolanda Harris, Lauren Krupp, Tim E. Lotze, Sabeen Lulu, Jayne Ness, Cody Olsen, Erik Roan, Moses Rodriguez, John Rose, Timothy C. Simmons, Tillema Jan-Mendelt Tillema, Wendy Weber, Bianca Weinstock-Guttman, Helen TremlettDouglas W. Fadrosh, Ali A. Faruqi, Janace Hart, Shelly Roalstad, Jennifer Graves, Collin M. Spencer, Susan V. Lynch, Scott S. Zamvil, Emmanuelle Waubant

Research output: Contribution to journalArticle

32 Citations (Scopus)

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.

Original languageEnglish (US)
Article number182
JournalBMC Neurology
Volume16
Issue number1
DOIs
StatePublished - Sep 21 2016

Fingerprint

Multiple Sclerosis
Biomarkers
Microbiota
Pediatrics
Fusobacteria
Bacteroidetes
rRNA Genes
Linear Models
Blood Cells
Flow Cytometry
Cytokines
T-Lymphocytes
Pharmaceutical Preparations
Gastrointestinal Microbiome

Keywords

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

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Aaen, G., Belman, A., Benson, L., Casper, C., Chitnis, T., Gorman, M., ... Waubant, E. (2016). Associations between the gut microbiota and host immune markers in pediatric multiple sclerosis and controls. BMC Neurology, 16(1), [182]. https://doi.org/10.1186/s12883-016-0703-3

Associations between the gut microbiota and host immune markers in pediatric multiple sclerosis and controls. / Aaen, Greg; Belman, Anita; Benson, Leslie; Casper, Charlie; Chitnis, Tanuja; Gorman, Mark; Harris, Yolanda; Krupp, Lauren; Lotze, Tim E.; Lulu, Sabeen; Ness, Jayne; Olsen, Cody; Roan, Erik; Rodriguez, Moses; Rose, John; Simmons, Timothy C.; Jan-Mendelt Tillema, Tillema; Weber, Wendy; Weinstock-Guttman, Bianca; 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.

In: BMC Neurology, Vol. 16, No. 1, 182, 21.09.2016.

Research output: Contribution to journalArticle

Aaen, G, Belman, A, Benson, L, Casper, C, Chitnis, T, Gorman, M, Harris, Y, Krupp, L, Lotze, TE, Lulu, S, Ness, J, Olsen, C, Roan, E, Rodriguez, M, Rose, J, Simmons, TC, Jan-Mendelt Tillema, T, Weber, W, Weinstock-Guttman, B, Tremlett, H, Fadrosh, DW, Faruqi, AA, Hart, J, Roalstad, S, Graves, J, Spencer, CM, Lynch, SV, Zamvil, SS & Waubant, E 2016, 'Associations between the gut microbiota and host immune markers in pediatric multiple sclerosis and controls', BMC Neurology, vol. 16, no. 1, 182. https://doi.org/10.1186/s12883-016-0703-3
Aaen, Greg ; Belman, Anita ; Benson, Leslie ; Casper, Charlie ; Chitnis, Tanuja ; Gorman, Mark ; Harris, Yolanda ; Krupp, Lauren ; Lotze, Tim E. ; Lulu, Sabeen ; Ness, Jayne ; Olsen, Cody ; Roan, Erik ; Rodriguez, Moses ; Rose, John ; Simmons, Timothy C. ; Jan-Mendelt Tillema, Tillema ; Weber, Wendy ; Weinstock-Guttman, Bianca ; 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. / Associations between the gut microbiota and host immune markers in pediatric multiple sclerosis and controls. In: BMC Neurology. 2016 ; Vol. 16, No. 1.
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AU - Belman, Anita

AU - Benson, Leslie

AU - Casper, Charlie

AU - Chitnis, Tanuja

AU - Gorman, Mark

AU - Harris, Yolanda

AU - Krupp, Lauren

AU - Lotze, Tim E.

AU - Lulu, Sabeen

AU - Ness, Jayne

AU - Olsen, Cody

AU - Roan, Erik

AU - Rodriguez, Moses

AU - Rose, John

AU - Simmons, Timothy C.

AU - Jan-Mendelt Tillema, Tillema

AU - Weber, Wendy

AU - Weinstock-Guttman, Bianca

AU - Tremlett, Helen

AU - Fadrosh, Douglas W.

AU - Faruqi, Ali A.

AU - Hart, Janace

AU - Roalstad, Shelly

AU - Graves, Jennifer

AU - Spencer, Collin M.

AU - Lynch, Susan V.

AU - Zamvil, Scott S.

AU - Waubant, Emmanuelle

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