Associations Between Immune Markers and Gut Microbiota in Pediatric Multiple Sclerosis and Controls (S29.008)

Abstract

Background/objective: Little is known about 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 UCSF pediatric clinic provided stool and blood samples. MS cases were within 2 years of onset. Controls were free from autoimmune disorders (asthma and eczema allowed). The 16S rRNA gene was amplified from extracted DNA and bacterial profiles were generated using QIIME (Quantitative Insights Into Microbial Ecology). Peripheral blood mononuclear cells were isolated, and Treg (CD4+CD25+CD127lowFoxP3+) frequency and intracellular cytokine production (IFN-γ, IL-17A, IL-4, IL-10) by CD4 T cells were evaluated by flow cytometry. These immune markers were compared between cases and controls and associations with the gut microbiota explored. Results: Twenty-four children (15 relapsing-remitting MS cases, 9 controls) with a mean age of 12.6 years (SD=4.18; range 4-18) were included; 9/24 (38[percnt]) were boys. The mean MS disease duration was 10.0 months; 7 were disease-modifying drug exposed. Although immune markers (e.g. IFN-g, IL-17, IL-10, CD4+CD25+Foxp3+ Treg) did not differ between groups (all p>0.05), divergence between cases and controls in the associations with the gut microbiota and host immunological markers were observed. IL-17+ T cells were positively associated with overall richness and evenness for cases (r=0.665, p=0.018 and r=0.545, p=0.067, respectively), but not controls (r=-0.644, p=0.061 and r=-0.728, p=0.026, respectively). At the phylum level, IL-17 T-cells were inversely associated with Bacteroidetes abundance for cases (r=-0.719, p=0.008) but not controls (r=0.320, p=0.401). Conversely, Tregs ([percnt] CD4+) significantly correlated with Fusobacteria for controls (r=0.817, p=0.007), but not cases (r=0.129, p=0.646 ). Conclusions: Associations were found between gut microbiota and host immunological (blood) markers which differed for children with and without MS. Further work is needed to validate and explore these divergent findings and understand their potential role in MS.

Disclosure: Dr. Tremlett has received personal compensation for activities with Bayer Pharmaceuticals, Teva Pharmaceuticals, Novartis Canada and Biogen. Dr. Fadrosh has nothing to disclose. Dr. Farqui has nothing to disclose. Dr. Hart has nothing to disclose. Dr. Roalstad has nothing to disclose. Dr. Graves has nothing to disclose. Dr. Spencer has nothing to disclose. Dr. Lynch has received personal compensation for activities with Janssen Pharmaceuticals, Regeneron, Boston Consulting Group, Theravance, and Novartis as a consultant. Dr. Zamvil has received personal compensation for activities with Biogen Idec, Teva Neuroscience, EMD Serono-Pfizer, Novartis and Genzyme. Dr. Waubant has received personal compensation for activities with Roche Diagnostics Corporation, Genzyme Corporation, and Novartis. Dr. Waubant has received research support from Roche Diagnostics Corporation, Biogen Idec, and Novartis.