1. 30 AUGUST 2012 | VOL 488 | NATURE R3 Jae Ryung Shin/Prof. Sang Youl Rhee

2.  The administration of low doses of antibacterial agents Promotes the growth of farm animals Weight gain by as much as 15%  The vertebrate GI tract contains an complex and dense microbial environment Bacterial constituents that affect the immune responses of populations of reactive host cells

3.  The GI tract also is a locus of hormone production Energy homeostasis (insulin, glucagon, leptin and ghrelin) Growth (glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1))  Alterations in the populations of the GI microbiota Change the intra-community metabolic interactions Modify caloric intake by using carbohydrates such as cellulose

4.  Full (therapeutic) dose antibiotic treatments alter both the composition of the GI microbiota and host responses to specific microbial signals  However, the effects of exposure to subtherapeutic antibiotic dosages have not been described  Murine model of early-life subtherapeutic antibiotic treatment (STAT) Explore how antibiotic exposure modulates host metabolic phenotypes

5.  Female C57BL/6J mice were given penicillin, vancomycin, penicillin plus vancomycin, or chlortetracycline(1mg antibiotic per g body weight) via drinking water, or no antibiotics (control)  Body composition determined using dual energy X-ray absorptiometry (DEXA)  At death, blood, caecal contents, liver and visceral adipose tissue were collected, and serum hormones measured

6.  DNA was extracted from caecal contents and faecal pellets, and 16S rRNA gene v3 regions were barcoded and sequenced, using 454-FLX Titanium chemistry  Quality-filtered sequences were processed through the QIIME pipeline and analysed in the R statistical environment  Quantitative PCR assessed taxa and metabolic genes of interest, and expression profiling of hepatic RNA was performed by microarray

8. DEXA scanning P+V P V Ct

10. Figure 3 | Changes in the faecal gut microbiome after 50 days of STAT bacterial counts or fungal census Firmicutes Lachnospiraceae bloom

11.  Butyryl coA transferase(BCoAT) and Formyl tetrahydrofolate synthetase(FTHFS) have a role in metabolism of carbohydrates into short-chain fatty acid(SCFAs)  STAT treatment is affecting composition of genes related to SCFAs, probably in antibiotic-specific ways STAT colonic microbiome alters SCFA metabolism

12. Increased SCFA concentrations and butyrate/acetate levels STAT-induced adiposity phenotypes Stimulates adipogenesis

13. 22 gene 47 gene STAT alters hepatic metabolism of fatty acids and lipids

14.  The STAT exposures selected for micro-biota with increased metabolic activity that were able to extract a higher proportion of calories from dietary complex carbohydrates  The increased SCFA concentrations Lipogenesis Caloric absorption Weight gain