Association between Early Antibiotic Exposure and Gut Microbiome Alterations in Neonates: A Systematic Review and Meta-Analysis

Abstract

This systematic review and meta-analysis aimed to quantify the effects of early antibiotic exposure on the composition of the neonatal gut microbiome and health outcomes by synthesizing evidence from PubMed, MEDLINE, EMBASE, Cochrane Library and Google Scholar (2020-2026); and using a DerSimonian–Laird random-effects model for standardized mean differences (SMD) and odds ratios (OR) with 95% confidence intervals. Thirty-four studies (42,680 neonates) met inclusion criteria and quantitative pooling revealed significantly lower alpha diversity in neonates who were exposed to antibiotics (pooled SMD = −1.42; 95% CI: −1.78 to −1.06; I² = 68.4%; p < 0.001) and severe Bifidobacterium depletion (pooled SMD = −1.89; 95% CI: −2.31 to −1.47; I² = 72.1%; p < 0.001); binary outcomes showed significantly higher odds of asthma (OR = 1.52; 95% CI: 1.26 to 1.81; I² = 76.1%; p < 0.001), atopic dermatitis (OR = 1.41; 95% CI: 1.20 to 1.64; I² = 74.3%; p < 0.001), inflammatory bowel disease (OR = 1.73; 95% CI: 1.1 There were significant differences between preterm and term infants in terms of dysbiosis (SMD = −2.18 vs. −0.96; p for interaction < 0.001), and gestational age (β = 0.14 per week earlier, p = 0.003) and antibiotic duration (β = 0.22 per additional day, p = 0.001) were found to be significant moderators of between-study heterogeneity, accounting for 54.8% of this heterogeneity; Egger's test for publication bias found no significant publication bias (intercept = 0.84; p = 0.082). This thorough meta-analysis offers quantitative support for the impacts of early antibiotic exposures on the developing neonatal gut microbiome and their consequences for allergic, inflammatory and infectious diseases, and suggests that stewardship of antibiotic use –especially duration and spectrum – is the most promising intervention to maintain the integrity of the neonatal gut microbiome.