Abstract

The early-life gut microbiota plays a crucial role in promoting health, with infancy characterized by lower bacterial abundance and diversity compared to adulthood. This microbiota undergoes significant changes in response to environmental factors such as an obesogenic high-fat (HF) diet or antibiotic treatment. Disruption to the early-life microbiota is linked to lasting impacts on health, including increased risk for obesity. In this study, we investigate how early-life antibiotic treatment exacerbates HF diet-induced obesity in young mice. We find that antibiotic exposure leads to greater adiposity and metabolic dysfunction during HF diet consumption. Depletion of Lactobacillus species from the small intestine microbiota appears to be a key driver of excess fat accumulation, with dysregulation of lipid metabolism observed. Furthermore, we identify phenyllactic acid (PLA), a microbiota-derived metabolite, as a potential protective factor against obesity induced by early-life exposure to antibiotics and an HF diet. These findings underscore the intricate interplay between early-life gut microbiota, diet, and host metabolism in childhood obesity development.