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

J Nutr. 2024 May 23:S0022-3166(24)00292-X. doi: 10.1016/j.tjnut.2024.05.015. Online ahead of print.


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.

PMID:38795745 | DOI:10.1016/j.tjnut.2024.05.015

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