TY - JOUR
T1 - Associations between the gut microbiota and host immune markers in pediatric multiple sclerosis and controls
AU - US Network of Pediatric MS Center
AU - Aaen, Greg
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
N1 - Funding Information:
Scott Zamvil receives research grant support from the NIH (1RO1 NS092835), the NMSS (RG 4768, RG5180. RG5179), The Guthy Jackson Charitable Foundation, The Maisin Foundation, Biogen Idec, Inc. and Teva Pharmaceuticals, Inc. Currently, Dr. Zamvil serves Deputy Editor of Neurology, Neuroimmunology and Neuroinflammation and is a member of the advisory board for the International Society of Neuroimmunology. He has served as a consultant and received honoraria from Biogen-Idec, EMD-Serono, Genzyme, Novartis, Questcor, Roche, and Teva Pharmaceuticals, Inc., and has served or serves on Data Safety Monitoring Boards for Lilly, BioMS, Teva and Opexa Therapeutics Emmanuelle Waubant is funded by the NIH, the NMSS, and the Race to Erase MS. She has received honorarium for one educational lecture from Genentech. She volunteers on an advisory board for a Novartis trial. She has received honorarium or travel support from ACTRIMS, ECTRIMS, and AAN.
Funding Information:
Helen Tremlett is funded by the Canada Research Chair program. She has received research support from the National Multiple Sclerosis Society, the Canadian Institutes of Health Research, and the UK MS Trust; speaker honoraria and/or travel expenses to attend conferences from the Consortium of MS Centres (2013), the National MS Society (2012, 2014), Bayer Pharmaceuticals (2010), Teva Pharmaceuticals (2011), ECTRIMS (2011, 2012, 2013, 2014), UK MS Trust (2011), the Chesapeake Health Education Program, US Veterans Affairs (2012), Novartis Canada (2012), Biogen Idec (2014), American Academy of Neurology (2013, 2014, 2015). Unless otherwise stated, all speaker honoraria were either donated to an MS charity or to an unrestricted grant for use by her research group. Douglas Fadrosh has no disclosures. Ali Faruqi has no disclosures. Janace Hart has no disclosures. Shelly Roalstad has no disclosures. Jennifer Graves is funded by the Race to Erase MS and the National MS Society. Collin Spencer has no disclosures. Susan Lynch is funded by the NIH, Sloan Foundation, Cystic Fibrosis Foundation, Broad Foundation, Jannsen Pharmaceuticals, Gilead and Pfizer. She has recently or currently acts as an ad hoc consultant for Janssen Pharmaceuticals, Regeneron, Boston Consulting Group, Theravance and Novartis. She is an Associate Editor for Microbiome, a members of the Scientific Advisory Board of Second Genome and has received honoraria for lectures from American Thoracic Society, American Academy of Allergy Asthma and Immunology, Georgia Regents University, Alta Bates and Kaiser Permanente. She holds four patents and has received royalties for IP licensed by KaloBIos Inc.
Funding Information:
This work was supported in part by the National MS Society RG4861A3/1 (PI Waubant), National Institutes of Health NS071463 (PI Waubant), The Race to Erase MS (PI Waubant) and the Canada Research Chair program (PI Tremlett). The funding source(s) had no role in the study design, collection, analysis or interpretation of the data, or in the decision to submit the article for publication.
Publisher Copyright:
© 2016 The Author(s).
PY - 2016/9/21
Y1 - 2016/9/21
N2 - 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.
AB - 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.
KW - 16S rRNA
KW - Case-control study
KW - Disease-modifying drugs
KW - Gut microbiota
KW - Immune markers
KW - Microbiota-immune balance
KW - Pediatric multiple sclerosis
KW - Risk factors
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U2 - 10.1186/s12883-016-0703-3
DO - 10.1186/s12883-016-0703-3
M3 - Article
AN - SCOPUS:84988462424
VL - 16
JO - BMC Neurology
JF - BMC Neurology
SN - 1471-2377
IS - 1
M1 - 182
ER -