EARLY-LIFE ANTIBIOTIC EXPOSURE, THE DEVELOPING GUT MICROBIOME, AND LONG-TERM METABOLIC AND IMMUNE HEALTH: A PROSPECTIVE BIRTH-COHORT ANALYSIS

Abstract

The first years of life represent a critical window during which the gut microbiome assembles and calibrates host metabolism and immunity. Antibiotics, though frequently prescribed in infancy, disrupt this assembly, raising concern about lasting health consequences. This prospective birth-cohort study examined the effect of early-life antibiotic exposure on gut microbiome development and subsequent metabolic and immune outcomes. Stool samples from 400 infants (198 antibiotic-exposed, 202 unexposed within the first year) were profiled by 16S ribosomal RNA gene sequencing at 1, 3, 6, 12, and 24 months, and children were followed to age five. Antibiotic exposure was associated with reduced bacterial diversity that persisted through 24 months (group × age F(4,1592)=9.3, p<.001), a transient bloom of Proteobacteria with depletion of Actinobacteria, and a lower microbiome-for-age z-score, indicating delayed maturation. Exposed children had higher body-mass-index z-scores at age five, with a dose- and timing-dependent gradient (earliest, repeated exposure showing the largest effect), and elevated odds of overweight (OR=1.42) and asthma or wheeze (OR=1.66). These findings support the hypothesis that early-life antibiotics perturb a developmentally sensitive microbial window with downstream metabolic and immune consequences, underscoring the importance of antibiotic stewardship in early childhood. (All data are simulated for methodological demonstration and do not derive from human participants.)