The association between early life antibiotic use and allergic disease in young children: recent insights and their implications

ABSTRACT

Introduction: Greater prescribing of antibiotics to infants has coincided with an epidemic of allergic disease. Through meta-analytic synthesis, accumulating evidence from prospective or database cohorts suggests a link between infant antibiotic treatment and the development of atopy. Stronger associations seen with multiple course and broad-spectrum antibiotic treatment add to biological plausibility. A major bias, confounding by indication, has been addressed in studies on antibiotic treatment of conditions which do not precede allergic disease.

Areas covered: Our review provides an up-to-date synthesis of the current literature on associations between infant antibiotic exposure and future allergic disease. We discuss methods that assist in reducing study bias and look at new insights from studies of the infant gut microbiome.

Expert commentary: Large-scale profiling of the gut microbiome provides a new tool for disentangling biases found in observational studies of infant antibiotic use. To date, microbial dysbiosis of the infant gut has been reported to predict allergic disease independent of antibiotic exposure up to 3 months after birth. However, these studies have not accounted for antibiotic treatment in later infancy. Continued study of the infant gut microbiome, mycobiome, or resistome will provide a closer link to antibiotic treatment or refute it as a cause of allergic disease.

KEYWORDS:

• Antibiotics
• asthma
• allergic disease
• infants
• microbiome
• mycobiome
• resistome

Key issues

• Global consumption of antibiotics has risen substantially over time, and in developed countries the increased prescribing of antibiotics, namely of broad-spectrum antibiotics, in early life has coincided with an epidemic of childhood asthma and allergic diseases.

• Through meta-analytic synthesis of the literature, there is evidence of a positive association between antibiotic exposure in infancy and later development of allergic disease; however, results have been hampered by issues of reverse causality and confounding by indication.

• New evidence from large individual or combined cohorts and regional database longitudinal studies continues to support this association, which is strengthened by the biological plausibility of stronger associations seen with multiple course and broad-spectrum antibiotic treatment.

• A major source of bias, confounding by indication, has been addressed in studies of the antibiotic treatment of conditions, i.e. urinary tract infection, which do not precede allergic disease. Large-scale gene sequencing of the infant gut microbiome has provided a further tool to reduce this bias.

• In a limited number of studies to date, microbial dysbiosis of the infant gut has been found to predict allergic disease independent of antibiotic exposure up to 3 months after birth. These studies have not accounted for antibiotic treatment in later infancy, a strong risk factor for allergic disease.

• Continued study of the infant gut microbiome, mycobiome, or even resistome will provide a closer link to antibiotic treatment or refute it as a cause of allergic disease development.

Declaration of interest

AL Kozyrskyj declares a SyMBIOTA Canadian Institutes of Health Research grant number 227312. MC Arrieta declares research funding from NSERC, CFI, CIHR, Alberta Health Services and The University of Calgary. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper is not funded.