Antibiotics in early life alter the murine colonic microbiome and adiposity

Abstract

Antibiotics administered in low doses have been widely used as growth promoters in the agricultural industry since the 1950s, yet the mechanisms for this effect are unclear. Because antimicrobial agents of different classes and varying activity are effective across several vertebrate species, we proposed that such subtherapeutic administration alters the population structure of the gut microbiome as well as its metabolic capabilities. We generated a model of adiposity by giving subtherapeutic antibiotic therapy to young mice and evaluated changes in the composition and capabilities of the gut microbiome. Administration of subtherapeutic antibiotic therapy increased adiposity in young mice and increased hormone levels related to metabolism. We observed substantial taxonomic changes in the microbiome, changes in copies of key genes involved in the metabolism of carbohydrates to short-chain fatty acids, increases in colonic short-chain fatty acid levels, and alterations in the regulation of hepatic metabolism of lipids and cholesterol. In this model, we demonstrate the alteration of early-life murine metabolic homeostasis through antibiotic manipulation. Treatment of young mice with low levels of antibiotics results in increases in adiposity and causes both a change in the composition of the intestinal microbial community and an alteration in the activity of microbial metabolic pathways, leading to increased short-chain fatty acid production. Continuous treatment with low levels of antibiotics has for decades been used to enhance body weight in livestock, yet the mechanisms underlying this effect are unclear. Using a similar approach in young mice, these authors show that subtherapeutic doses of antibiotic increase the body's fat mass, cause changes in the composition of the intestinal microbial community and alter the activity of microbial metabolic pathways that lead to short-chain fatty-acid production. These findings highlight the importance of certain microbes in maintaining normal metabolic activity.