Investigating Early Life Dynamics of Human Gut Antibiotic Resistome and Its Potential Links with Health and Disease

Abstract

The human gut microbiome plays a critical role in health and diseases. This complex community of microorganisms is established early in life and undergoes significant changes during infancy, a period crucial for long-term health. In infants, the gut microbiome is particularly dynamic, with the mode of delivery being one of the initial factors influencing it. Despite ongoing research, there are gaps in understanding the dynamics of ARG acquisition, evolution and associations to environmental factors such as diet, mode of delivery, maternal antibiotic exposures, infant’s antibiotic exposure, and water type used by infants. This thesis aims to characterize ARGs in infants during first year of life and investigate their associations with metadata variables including mode of delivery, maternal antibiotic consumption, and environmental factors. One way to explore these resistome dynamics is through the study of antibiotic resistome analysis and how these ARGs are associated with mode of delivery and environmental factors. This study combine metagenomics techniques with gene prediction and gene catalogue construction tools like Prodigal and MMseqs2. ARGs were identified through CARD database by using DIAMOND, according to the results infants delivered via Csection delivery had a higher abundance of ARGs which clear pattern of ARG prevalence associated with delivery techniques. Notably, infants exposed to antibiotics whether directly or through maternal source exhibited a disrupted microbiome and increased risk of harboring ARGS potentially lead them to immunological dysregulation and illness like obesity, inflammatory bowel disease, and cardiovascular disorders. This study emphasizes the complex interactions between environmental variables and infant gut microbiome xiv underscoring the gut microbiota, underscoring the necessity for focused approaches to slow the spread of ARGs. This study will help to prevent antibiotic resistance and its effects on human health by deepening our understanding of antibiotic resistome dynamics their relationship to early life exposures.