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Early-life exposures associated with antibiotic use and risk of subsequent Crohn's disease
Hans Hildebrand1, Petter Malmborg, Johan Askling
1Department of Women and Child Health, Astrid Lindgren Children's Hospital, Stockholm, Sweden.
Insights
Early childhood pneumonia, a common childhood illness, is linked to an increased risk of developing Crohn's disease later in life. This suggests early life exposures may impact immune development and gut health, potentially triggering inflammatory bowel disease.
Area of Science:
- Gastroenterology
- Immunology
- Pediatrics
Background:
- Crohn's disease (CD) is an inflammatory bowel disease (IBD) linked to aberrant immune responses to gut microbiota.
- Immune tolerance to gut flora develops in infancy, making early life exposures critical.
- Disruptions in early gut colonization may increase CD risk.
Purpose of the Study:
- To investigate if antibiotic therapy in early childhood (birth to age 5) alters gut colonization patterns.
- To test the hypothesis that early antibiotic use increases the risk of developing Crohn's disease.
Main Methods:
- A Swedish population-based case-control study identified 1098 CD patients and 6550 controls.
- Data on inpatient diagnoses associated with antibiotic therapy between birth and age 5 were collected.
- Pneumonia and otitis media were the primary diagnoses analyzed due to their frequency.
Main Results:
- Pneumonia before age 5 showed a statistically significant association with pediatric and adult CD.
- Odds ratios for CD were 2.74 (95% CI: 1.04-7.21) for pediatric CD and 4.94 (95% CI: 1.83-13.23) for adult CD.
- Pneumonia after age 5 was not significantly associated with CD risk.
Conclusions:
- Pneumonia in early childhood (prior to age 5) is associated with subsequent Crohn's disease.
- This association may indicate underlying susceptibility or a causal link.
- Early life exposures, potentially through gut dysbiosis, may influence immune function and elevate CD risk.
Objective:
An inappropriate immune response to normal bowel flora is implicated in the etiology of Crohn's disease. Tolerance to bowel flora develops in infancy, so factors disrupting normal patterns of bowel colonization may increase the risk of Crohn's disease. The aim of this study was to test the hypothesis that antibiotic therapy between birth and age 5 years may disrupt the pattern of bowel colonization and increase the risk of Crohn's disease.
Material And Methods:
Some 1098 patients with Crohn's disease and 6550 controls matched by delivery unit, year of birth, sex, and born between 1973 and 1997 were identified through the Swedish population registers. Seven inpatient diagnoses between birth and age 5 years associated with antibiotic therapy were identified by prospectively recorded data.
Results:
Of the seven diagnoses, only pneumonia and otitis media were sufficiently common for use in the analyses. Pneumonia and otitis media were not independent of each other in their association with Crohn's disease and the more important association was with pneumonia. Pneumonia by age 5 years was statistically significantly associated with both pediatric- and adult Crohn's disease, with odds ratios (and 95% CI) of 2.74 (1.04-7.21) and 4.94 (1.83-13.23), respectively. Pneumonia after age 5 years was not statistically significantly associated with Crohn's disease.
Conclusions:
Pneumonia prior to age 5 years, but not later, was associated with subsequent Crohn's disease and this may represent either susceptibility or causation. The results are consistent with early exposures influencing immune function, such as through disruption of bowel colonization, and thus increasing the risk of Crohn's disease.
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