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 hypothesized 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 hormones 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.

The gut microbiota and inflammatory noncommunicable diseases: Associations and potentials for gut microbiota therapies

“…Notably, more subtle manipulation with low doses of antibiotics in early life (at levels likely to be encountered in human food) increased the risk of adiposity, with significant effects on short-chain fatty acid (SCFA) levels, and in the regulation of hepatic metabolism of lipids and cholesterol 26 . Equally fascinating are results from experimental models reporting changes in behaviour and gene expression in the brain following changes in the gut microbiota 6,8 .…”

Symbiosis as a General Principle in Eukaryotic Evolution

“…The hyperlipidemia and hyperglycemia displayed by Drosophila containing mutant A. pomorum are reminiscent of the elevated lipid and glucose levels in the laboratory mouse treated with antibiotics that alter the composition of the gut microbiota (Cho et al 2012). The gut microbiota of the mouse can also be altered by diet or mutation, especially of the mouse immune system and nutrient signaling, with correlated phenotypic lesions, especially in nutrient allocation and immune function (Maslowski and Mackay 2011; Claesson et al 2012;Maynard et al 2012).…”

Breast milk, microbiota, and intestinal immune homeostasis

“…The ensuing dysbiosis has been associated with an increase in diseases such as asthma (8) and celiac disease (9). In addition, perinatal use of antibiotics, particularly in premature infants, can interfere with the balance of bacterial phyla and diversity of individual species and makes the newborn much more susceptible to infectious inflammatory diseases (10,11). Long-term follow up on the use of antibiotics during the first year of life has shown an association with an increased incidence of inflammatory bowel disease (12), asthma (13), and increased weight gain leading to adult obesity (14).…”