1190-P: Elevated Serum IgA is Associated with Relatively Preserved Stool Microbiome at the Onset of Pediatric Type 1 Diabetes (T1D)

Introduction & Objective: People with or at risk for T1D have decreased stool microbiome diversity. Secretory IgA modifies and is modified by the gut microbiota, but the role of serum IgA is less understood. Serum IgA is nonetheless elevated in 20% of children with T1D. We aimed to determine whether elevated serum IgA levels are associated with altered gut microbiome characteristics at the onset of pediatric T1D.

Methods: We prospectively enrolled children (2-18 years old) diagnosed with T1D within the past 6 months with age-adjusted serum IgA levels in the normal range (T1D-NL-IgA, n=18) or elevated (T1D-HI-IgA, n=14) and nondiabetic children, including siblings (NoDM, n=15). Using a single stool sample from each participant, we performed 16Sv4 rRNA gene sequencing and characterized the gut microbiome with respect to IgA status and other clinical measures. Microbiome alpha and beta diversity were tested via linear regression and Permutational Analysis of Variance (PERMANOVA), respectively, while differences in taxa were determined by Analysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC). All microbiome analyses were adjusted for age, race, and sex.

Results: The T1D-HI-IgA group, compared to T1D-NL-IgA, had significantly lower BMI percentile (25% vs 48%, p=0.042) and higher HbA1c (mean 13.2% vs 11.1%, p<0.001) but similar glucose levels (p=0.41) at onset. Alpha diversity decreased with higher glucose (Observed OTUs: p=0.093; Inverse Simpson: p=0.007) but not with C-peptide. The T1D-NL-IgA group had the lowest bacterial richness (p=0.009 vs NoDM, p=0.048 vs T1D-HI-IgA) and greater differences in relative abundance of core taxa, including lower levels of Sutterella, Prevotella-9, and Akkermansia, and higher levels of Agathobacter, Lachnospira, and Parasutterella.

Conclusion: Our results suggest that elevated serum IgA at onset of pediatric T1D may mark a longer, slower preclinical stage, with a more preserved gut microbiome profile.