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.
