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Effects of early antibiotic exposure on host metabolism
The intestinal microbiota, consisting of trillions of bacterial, viral, and fungal cells, can influence growth and development. From infancy through early childhood, the microbial community develops with a succession of key organisms that likely have important roles in shaping metabolic health. Disrupting these ancient patterns of microbe-host maturation may have lasting metabolic consequences. Low-dose antibiotics, especially administered during infancy, can increase weight gain and feed efficiency in a wide variety of host species. To identify key members of the microbiota that may participate, we administered low-dose penicillin (LDP) to mice, measured changes in body composition, and characterized changes in the microbiota by high-throughput sequencing. We found that LDP administered only during the first 4 weeks of life increased fat mass later in adulthood, despite the fact that the microbiota recovered, indicating microbiota interactions in infancy may be critical determinants of long-term host metabolic effects. In addition, LDP enhanced the effect of high-fat diet induced obesity. The growth promotion phenotype was transferrable to germ-free hosts by LDP-selected microbiota, showing that the altered microbiota, not antibiotics per se, play a causal role. Four different bacteria were consistently suppressed during infancy in multiple independent experiments, suggesting that they may have beneficial roles in metabolic development. These studies characterize important variables in early-life microbe-host metabolic interaction and identify several bacteria consistently linked with metabolic alterations.