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 language | English (US) |
|---|---|
| Article number | 182 |
| Journal | BMC Neurology |
| Volume | 16 |
| Issue number | 1 |
| DOIs | |
| State | Published - Sep 21 2016 |
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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
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 journal › Article
}
TY - JOUR
T1 - Associations between the gut microbiota and host immune markers in pediatric multiple sclerosis and controls
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
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
UR - http://www.scopus.com/inward/record.url?scp=84988462424&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84988462424&partnerID=8YFLogxK
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 -