Dynamics of Infant Gut Resistome and Mobilome: Impact of Gestational Age, Antibiotics, Probiotics, and Other Early-Life Factors

Abstract

Antimicrobial resistance (AMR) is a growing global health concern, particularly in vulnerable populations such as infants. The gut microbiota, which plays a crucial role in health and disease, is shaped by early-life factors like birth mode, feeding type, antibiotic exposure, probiotics, and hospitalisation. However, how these factors influence antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) in the infant gut remains poorly understood. This thesis investigates how early-life exposures affect the resistome (collection of ARGs) and mobilome (collection of MGEs) and assesses whether probiotics can help mitigate AMR. By integrating shotgun metagenomics, bioinformatics, statistical modelling, and machine learning, this research provides a comprehensive analysis across diverse infant cohorts. The findings show that <i>Escherichia coli</i> plays a dominant role in shaping the infant resistome and mobilome. Paper I demonstrates that probiotic supplementation in extremely preterm infants reduces pathogenic bacteria, promotes microbiota maturation, and lowers ARG abundance. Paper II, a large-scale meta-analysis, reveals that birth mode, gestational age, feeding type, and geography significantly influence resistome and mobilome composition. Notably, over half of ARGs were linked to plasmids in bacteria like <i>Escherichia coli</i> and <i>Enterococcus faecalis</i>, highlighting the role of horizontal gene transfer in AMR spread. Paper III reinforces the benefits of probiotics, showing that in full-term infants, they slow the replication of <i>Escherichia coli</i>, reduce ARG and MGE loads, and contribute to a healthier gut microbiota. These insights provide a foundation for microbiota-targeted strategies to combat AMR in early life. By improving AMR surveillance and informing probiotic-based interventions, this research supports efforts to reduce antibiotic resistance and promote healthier microbial development in infants.