Genetic Risk for Type 1 Diabetes Profoundly Influences the Core Gut Microbiome in Children

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All of the gut microbiome associations with type 1 diabetes autoimmunity to date have been discovered in cohorts where all subjects are at high genetic risk for the disease. The design of such cohorts precludes an assessment of the influence HLA high risk alleles on gut microbiome composition. This question is addressed here by using stool samples from the general population All Babies in Southeast Sweden (ABIS) cohort where most children are at no genetic risk for type 1 diabetes. A proportion of ABIS children do possess high risk alleles including DR3/DQ2, DR4/DQ8, and DRB1. DNA from stool samples, collected at one year of age from 441 ABIS children (169 at high genetic risk), stored at -80°C, was extracted and 16S rRNA amplified, sequenced, and analyzed. The core microbiome for each category was computed by including only those reads from taxa found in at least 70% of all subjects within that group. The core microbiomes of the two groups were readily separated by PCoA (Fig. 1) and were significantly different (p=0.001). Each core microbiome comprised about 65% of the reads collected. Bifidobacterium was significantly higher in the no-risk group while Veillonella was higher in the risk group. Thus, HLA risk alleles appear to influence the core gut microbiome and posit a novel mechanism whereby the microbiome may influence the pathogenesis of type 1 diabetes. Disclosure J. Russell: None. L. Roesch: None. M.A. Atkinson: Other Relationship; Self; Patent Issued. D. Schatz: None. E.W. Triplett: None. J. Ludvigsson: None.