Antibiotic Use and Later Risk of Celiac Disease: A Nationwide Case-Control and Sibling Analysis

BACKGROUND & AIMS: Antibiotic exposure has, albeit inconsistently, been linked to future celiac disease (CD), but may reflect health care-seeking behavior or treatment of undiagnosed CD. We examined prior antibiotic use in individuals with biopsy-verified CD vs their matched general population comparators and siblings. We also compared associations with individuals with normal mucosa. METHODS: This nationwide Swedish study (2007-2023) assessed antibiotic use up until 1 year before diagnosis/matching in 27,789 individuals with biopsy-verified CD, 133,451 comparators, and 33,112 siblings. Secondary analyses included individuals with histologically normal mucosa (n = 225,548) vs matched comparators (n = 1,089,796). Odds ratios (aORs) were adjusted for comorbidities, socioeconomic status, and health care use. RESULTS: Earlier antibiotic exposure was more common in CD (69%) than in comparators (63%; aOR, 1.24; 95% confidence interval [CI], 1.21-1.28). Restricted analyses to antibiotics ≥5 years before CD diagnosis yielded an aOR of 1.15 (95% CI, 1.11-1.19). The association increased with the number of dispensations (aOR, 1.21; 95% CI, 1.17-1.25 for 1-2; 1.35; 95% CI, 1.30-1.41 for ≥3 vs none). The association between CD and prior antibiotics persisted in sibling comparisons (any use: aOR, 1.29; 95% CI, 1.24-1.35). An even stronger association with antibiotics was seen among individuals with normal mucosa (aOR, 1.50; 95% CI, 1.48-1.51), with a particularly elevated risk in those with ≥3 earlier dispensations (aOR, 1.80; 95% CI, 1.78-1.83). CONCLUSIONS: Individuals with CD were more often exposed to antibiotics before diagnosis than their general population comparators. However, an even stronger association with antibiotic use was seen in those with normal mucosa, suggesting that heightened surveillance rather than causality may contribute to the observed patterns. Although antibiotic stewardship remains important, CD concerns should not deter appropriate antibiotic use.