Contributions
Abstract: P287
Type: Poster
Abstract Category: Clinical aspects of MS - Paediatric MS
Background and objective: Little is known of the 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 old attending a University of California, San Francisco, USA paediatric clinic provided stool and blood. MS cases were within 2 years of onset. Controls were free from autoimmune disorders (asthma and eczema allowed). 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 (r) and adjusted linear regression, expressed as beta coefficients and 95% confidence intervals (CIs).
Results: Twenty-four children (15 relapsing-remitting MS and 9 controls), averaging 12.6 years were included. The mean MS disease duration was 10.0 months and 7 were disease-modifying drug exposed (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), but not controls (r=-0.644, p=0.061). Fusobacteria abundance was associated with Tregs for controls (r=+0.829, p=0.006; age-adjusted beta=0.32; 95%CI: 0.11-0.53, p=0.009), but not cases (r=-0.069, p=0.808). Bacteroidetes inversely associated with Th17 for cases (r=-0.719, p=0.008), not controls (r=+0.320, p=0.401). Findings remained significant for cases when disease duration or DMD adjusted (beta=-4.9e-6; 95%CI: -9.0 to -1.0), p=0.013 and -3.9e-6; 95%CI: -7.0 to -0.7, p=0.021, respectively).
Conclusions: Associations were found between gut microbiota and host immunological (blood) markers which differed for children with and without MS. Our observations motivate further exploration to both validate findings and to understand the potential disruption of the microbiota-immune balance so early in the MS course.
Disclosure:
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
Feng Zhu 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 volunteers as 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.
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 volunteers on an advisory board for a Novartis trial. She has received honorarium or travel support from ACTRIMS, ECTRIMS, and AAN.
The US Network of Pediatric MS Centers (authors listed in alphabetical order): Greg Aaen1, Jan-Anita Belman2, Leslie Benson3, Brittan Browning4, Charlie Casper4, Tanuja Chitnis3, Marc Gorman3, Yolanda Harris5, Lauren Krupp2, Tim E Lotze6, Sabina Lulu7, Jayne Ness5, Cody Olsen4, Erik Roan4, Moses Rodriguez8, John Rose4, Timothy C Simmons4, Mendelt Tillema8, Wendy Weber4, Bianca Weinstock-Guttman9
1. Loma Linda University, Loma Linda, CA, United States; 2. Stony Brook University, Stony Brook, NY, United States; 3. Harvard University, Cambridge, MA, United States; 4. University of Utah, Salt Lake City, UT, United States; 5. Mayo Clinic, Rochester, MN, United States; 6. Baylor College of Medicine, Houston, TX, United States; 7. University of California, San Francisco, San Francisco, CA, United States; 8. University of Alabama, Birmingham, AL, United States; 9. State University of New York at Buffalo, Buffalo, NY, United States
Abstract: P287
Type: Poster
Abstract Category: Clinical aspects of MS - Paediatric MS
Background and objective: Little is known of the 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 old attending a University of California, San Francisco, USA paediatric clinic provided stool and blood. MS cases were within 2 years of onset. Controls were free from autoimmune disorders (asthma and eczema allowed). 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 (r) and adjusted linear regression, expressed as beta coefficients and 95% confidence intervals (CIs).
Results: Twenty-four children (15 relapsing-remitting MS and 9 controls), averaging 12.6 years were included. The mean MS disease duration was 10.0 months and 7 were disease-modifying drug exposed (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), but not controls (r=-0.644, p=0.061). Fusobacteria abundance was associated with Tregs for controls (r=+0.829, p=0.006; age-adjusted beta=0.32; 95%CI: 0.11-0.53, p=0.009), but not cases (r=-0.069, p=0.808). Bacteroidetes inversely associated with Th17 for cases (r=-0.719, p=0.008), not controls (r=+0.320, p=0.401). Findings remained significant for cases when disease duration or DMD adjusted (beta=-4.9e-6; 95%CI: -9.0 to -1.0), p=0.013 and -3.9e-6; 95%CI: -7.0 to -0.7, p=0.021, respectively).
Conclusions: Associations were found between gut microbiota and host immunological (blood) markers which differed for children with and without MS. Our observations motivate further exploration to both validate findings and to understand the potential disruption of the microbiota-immune balance so early in the MS course.
Disclosure:
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
Feng Zhu 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 volunteers as 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.
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 volunteers on an advisory board for a Novartis trial. She has received honorarium or travel support from ACTRIMS, ECTRIMS, and AAN.
The US Network of Pediatric MS Centers (authors listed in alphabetical order): Greg Aaen1, Jan-Anita Belman2, Leslie Benson3, Brittan Browning4, Charlie Casper4, Tanuja Chitnis3, Marc Gorman3, Yolanda Harris5, Lauren Krupp2, Tim E Lotze6, Sabina Lulu7, Jayne Ness5, Cody Olsen4, Erik Roan4, Moses Rodriguez8, John Rose4, Timothy C Simmons4, Mendelt Tillema8, Wendy Weber4, Bianca Weinstock-Guttman9
1. Loma Linda University, Loma Linda, CA, United States; 2. Stony Brook University, Stony Brook, NY, United States; 3. Harvard University, Cambridge, MA, United States; 4. University of Utah, Salt Lake City, UT, United States; 5. Mayo Clinic, Rochester, MN, United States; 6. Baylor College of Medicine, Houston, TX, United States; 7. University of California, San Francisco, San Francisco, CA, United States; 8. University of Alabama, Birmingham, AL, United States; 9. State University of New York at Buffalo, Buffalo, NY, United States