Infant use of acid-suppressant medication, C. difficile colonization, and childhood body mass index and asthma in a Canadian cohort

Abstract Aims Acid-suppressive medication (ASM) therapy during infancy raises risk for C. difficile infection and potentially chronic disease development. We aimed to determine relationships between ASMs given to infants, the proton pump inhibitors (PPI) and histamine-2 receptor antagonists (H2RA), and preschool body mass index (BMI) and asthma and whether they were mediated by C. difficile colonization.Methods ASMs were parent-reported at age 3, 6 and 12 months in 1,025 infants from the CHILD Cohort Study. 16S microbiota sequencing and targeted qPCR for C. difficile was conducted in stool collected at 3-months. At age 5 years, asthma was physician diagnosed and age/sex adjusted BMI-z scores calculated. ASM use, asthma status and BMI-z score associations were assessed by regression, and mediation analyses conducted.Results Approximately 4% of infants received H2RAs, most before age 3 months. C. difficile colonization was twice as likely in 3-month-old infants receiving H2RAs (OR: 2.27, 95% CI: 1.13–4.51) and was associated with higher BMI-z scores at age 5 years (β: 0.31, 95% CI: 0.16, 0.46). Mediation models showed an indirect positive effect of H2RA use on 5-year BMI-z scores, mediated through C. difficile colonization (β: 0.065, 95% CI: 0.01, 0.13). These results were not obtained with PPIs, but sample size was small (1% of infants).Conclusion We found evidence of increased preschool BMI following H2RA use in infants that was mediated through C. difficile colonization. Further study on ASM use in infancy, the gut microbiome and pathways to body weight health outcomes is warranted.