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30 AUGUST 2012 | VOL 488 | NATURE R3 Jae Ryung Shin/Prof. Sang Youl Rhee
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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
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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
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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
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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
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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
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DEXA scanning P+V P V Ct
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Figure 3 | Changes in the faecal gut microbiome after 50 days of STAT bacterial counts or fungal census Firmicutes Lachnospiraceae bloom
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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
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Increased SCFA concentrations and butyrate/acetate levels STAT-induced adiposity phenotypes Stimulates adipogenesis
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22 gene 47 gene STAT alters hepatic metabolism of fatty acids and lipids
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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
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