The effect of antibiotics on the gut microbiome in children: a systematic review

Problem

Antibiotics are the most commonly prescribed medications in children. The gut microbiome is in a state of development up to 3-5 years old. Antibiotic exposure in adults has been shown to reduce microbiome diversity, richness and change microbial composition. Microbial dysbiosis (change from healthy state or imbalance of organisms) in childhood has been associated with obesity, Crohn’s disease, type 1 diabetes, asthma and an increase in opportunistic infections. Much uncertainty remains regarding the effect of antibiotics on the microbiome in children. This research aimed to review and appraise the evidence of the effect of antibiotics on the developing microbiome.

Approach

A systematic review of research investigating the impact of antibiotics on the microbiome of children (via Medline, Embase and Web of Science) up to February 2019 was carried out. Inclusion criteria were: studies of any design assessing the impact of (named) antibiotic exposure on gut microbiota; participants <18 years (excluding pre-term babies); assessment of microbial composition or richness or diversity; molecular techniques such as PCR or DNA analysis, comparable control group or baseline assessment and adequate study power/ statistical analysis. Quality was assessed using modified Newcastle Ottawa Scale and Jaccard indices.

Findings

The search identified 4668 publications of which 10 studies were eligible for inclusion (5 cohort, 3 randomized controlled trials and 2 cross sectional studies). Quality was assessed as good (7 studies) or fair (3 studies). The 10 studies included 1662 participants (aged 2-12) of which 448 received antibiotics (duration 2-10 days). In 9 studies there was <1 month between antibiotic exposure and initial microbiome analysis. Meta-analysis was not possible due to heterogeneity in study design and outcome measures. All studies reported a change in microbiome composition following antibiotic exposure. A significant change in the balance of species was reported in all studies (p<0.05). Significant reduction in microbiome diversity and/or richness was reported in 5 out of 6 studies (p<0.05). Four out of 6 studies reported a decrease in Bifodobacteria spp. which are thought to be beneficial to the gut microbiome. In one study macrolide exposure had a longer lasting effect on the microbiome (up to 2 years) than penicillins.

Consequences

This systematic review has found evidence of collateral damage to the microbiome as a result of antibiotic exposure in children. There is good evidence that antibiotics altered the balance of species and reduced microbiome diversity and beneficial bacteria, at least in the short term. General practitioners should be aware of the unintended effects of antibiotics on the microbiome, particularly when prescribing multiple courses in a short period of time. General practitioners should be aware that macrolides may be more damaging to the microbiome than penicillins. Further research should investigate the longer-term changes in the microbiome following antibiotic exposure and focus on mitigation strategies.