Gut inflammation markers, diet, and risk of islet autoimmunity in Finnish children – a nested case-control study

Background Gut dysbiosis and increased intestinal permeability have been reported to precede type 1 diabetes related autoimmunity. Role of gut inflammation in autoimmunity is not understood. Objectives To assess whether gut inflammation markers are associated with risk of islet autoimmunity, and whether diet is associated with gut inflammation markers. Methods A nested case-control sample of 75 case children with islet autoimmunity and 88 control children was acquired from the Finnish Type 1 Diabetes Prediction and Prevention cohort. Diet was assessed with 3-day food records, and calprotectin and human β-defensin-2 (HBD-2) were analyzed from stool samples at 6 and 12 months of age. Conditional logistic regression analysis was used in a matched case-control setting to assess risk of autoimmunity. Analysis of variance, independent samples t-test, and general linear model were used in secondary analyses to test associations of background characteristics and dietary factors with inflammation markers. Results In unadjusted analyses, calprotectin was not associated with risk of islet autoimmunity, while HBD-2 in the middle (odds ratio [OR] 3.23; 95% confidence interval [CI]: 1.03, 10.08) or highest tertile (OR 3.02; 95% CI: 1.05, 8.69) in comparison to the lowest at 12 months of age showed borderline association (P-trend=0.063) with higher risk of islet autoimmunity. Excluding children with cow’s milk allergy in sensitivity analyses strengthened the association of HBD-2 with islet autoimmunity, while adjusting for dietary factors and maternal education weakened it. At age 12 months, higher fat intake was associated with higher HBD-2 (β= 0.219; 95% CI: 0.110, 0.328), and higher intake of dietary fiber (β= -0.294; 95% CI: -0.510, -0.078), magnesium (β= -0.036; 95% CI: -0.059, -0.014), and potassium (β= -0.003; 95% CI: -0.005, -0.001) with lower HBD-2. Conclusions Higher HBD-2 in infancy may be associated with higher risk of islet autoimmunity. Dietary factors play a role in gut inflammatory status.