Infant Acid-Suppressant Medication, C. difficile Colonisation, and Childhood Body Mass Index in a Canadian Cohort

Area of Science:

• Pediatric Health
• Microbiome Research
• Gastroenterology

Background:

• Acid-suppressive medications (ASMs) are frequently used in infants.
• The gut microbiome plays a crucial role in early development and metabolic health.
• Potential links between early-life medication exposure, gut colonization, and long-term health outcomes require investigation.

Purpose of the Study:

• To investigate the relationship between infant use of acid-suppressive medications (ASMs), specifically proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs).
• To determine the association between ASM use and body mass index (BMI) in preschool children.
• To examine the mediating role of Clostridioides difficile (C. difficile) colonization in this relationship.

Main Methods:

• Parental reports of ASM use (H2RAs, PPIs) were collected from 1025 infants at 3, 6, and 12 months.
• Clostridioides difficile colonization was assessed using qPCR on stool samples at 3 months.
• Body mass index (BMI)-z scores were calculated for children at 5 years of age; regression and mediation analyses were performed.

Main Results:

• Infant H2RA use was associated with a twofold increased likelihood of C. difficile colonization at 3 months (OR: 2.27).
• C. difficile colonization at 3 months was linked to higher BMI-z scores at 5 years (β: 0.31).
• Mediation analysis revealed an indirect positive effect of H2RA use on 5-year BMI-z scores, mediated by C. difficile colonization (β: 0.065).

Conclusions:

• Infant exposure to H2RAs is associated with increased preschool BMI, potentially mediated by C. difficile colonization.
• These findings highlight the gut microbiome's role in mediating the effects of early-life medication use on childhood weight.
• Further research is warranted to understand the long-term implications of ASM use on infant gut health and subsequent metabolic outcomes.