ABSTRACT Antibiotic exposure during infancy disrupts gut microbiome assembly during a critical developmental window. Strategies to restore these ecosystems remain limited. In the REPAIR trial ( NCT06609980 ), eight infants were followed longitudinally; two received amoxicillin for otitis media, and one subsequently underwent autologous fecal microbiota transplantation (aFMT) using stool collected prior to antibiotic exposure. Shotgun metagenomics, Hi-C–assisted resistome profiling, and untargeted metabolomics were performed on samples collected before and after antibiotics. Amoxicillin treatment was associated with displacement of community structure, enrichment of antibiotic resistance genes (ARGs), and altered fecal metabolites, including short-chain fatty acids, bile acids, acylcarnitines, bilirubin derivatives, tricarboxylic acid (TCA) cycle metabolites, and amino acids. In the non-restored infant, microbiota composition and ARG profiles remained persistently altered during follow-up, accompanied by sustained metabolic divergence. In contrast, the aFMT-treated infant demonstrated convergence toward pre-antibiotic community structure, directional restructuring of ARG carriers —including reduction of β-lactam and tetracycline resistance genes— and metabolite profiles trending toward the pre-antibiotic baseline across analytical platforms. Although limited to a case-based comparison, these findings provide integrated ecological and functional evidence that aFMT may promote recovery following antibiotic perturbation during early-life microbiome development and support the rationale for larger controlled clinical trials. IMPORTANCE Antibiotic exposure in early life disrupts the developing gut microbiome during a critical window of host-microbe interaction. However, the extent to which these disturbances resolve naturally, or can be actively reversed, remains unclear. In this study, we use longitudinal sampling in infants to examine microbiome recovery following antibiotics, with and without autologous fecal microbiota transplantation (aFMT). We show that antibiotic exposure leads to coordinated disruptions in microbial composition, antibiotic resistance genes, and metabolic profiles. While partial recovery spontaneously occurs over time, faster and more extensive restoration toward the pre-antibiotic state is observed following aFMT. These findings provide insight into the ecological dynamics of microbiome reassembly in early life and highlight the potential of using controlled perturbations to understand microbiome resilience. CLINICAL TRIALS This study is registered with ClinicalTrials.gov as NCT06609980 .
Sun et al. (2026) studied this question.