Gastrointestinal Infections Modulate the Risk for Insulin Autoantibodies as the First-Appearing Autoantibody in the...

Area of Science:

• Pediatric immunology
• Gastroenterology
• Epidemiology

Background:

• Type 1 diabetes is an autoimmune disease where the body attacks insulin-producing islet cells.
• Early life environmental factors are suspected to trigger islet autoimmunity.
• Gastrointestinal infections (GIEs) are common in early childhood and have been investigated as potential triggers.

Purpose of the Study:

• To investigate the association between gastrointestinal infection episodes (GIEs) and the subsequent development of islet autoantibodies.
• To identify specific GIEs or pathogens associated with increased or decreased risk of islet autoantibodies.

Main Methods:

• A 10-year follow-up of 7,867 children from The Environmental Determinants of Diabetes in the Young (TEDDY) cohort.
• Assessment of GIEs in relation to the first appearance of autoantibodies against insulin (IAA) or GAD (GADA).
• Stool virome characterization in a nested case-control study.

Main Results:

• GIEs reported before 1 year of age were associated with increased IAA risk (OR 2.17), with Norwalk virus showing a strong association (OR 5.69).
• GIEs reported between 1 to <2 years of age correlated with a decreased IAA risk (OR 0.48).
• GIEs at other ages or 12-23 months prior to IAA also increased IAA risk (OR 2.04); GADA risk was associated with GIEs <6 months prior in children <4 years (OR 2.16).

Conclusions:

• Gastrointestinal infections show a complex, bidirectional association with islet autoantibody development.
• Norwalk virus is a potential environmental factor linked to increased IAA risk.
• The timing of GIEs relative to autoantibody development is crucial, with infections in the second year of life potentially protective against IAA.