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Regulation of host weight gain and lipid metabolism by bacterial bile acid modification in the gut


ABSTRACT: Alterations in the gastrointestinal microbiota have been implicated in obesity in mice and humans, but the conserved microbial functions that influence host energy metabolism and adiposity have not been determined. Here we show that bacterial bile salt hydrolase (BSH) controls a microbe-host dialogue which functionally regulates host lipid metabolism and weight gain. Expression of cloned BSH enzymes in the GI tract of gnotobiotic or conventional mice significantly altered plasma bile acid signatures and regulated transcription of key genes involved in lipid metabolism (PPARgamma angptl4), cholesterol metabolism (abcg5/8), gastrointestinal homeostasis (regIIIgamma) and circadian rhythm (dbp, per1/2) in the liver or small intestine. High-level expression of BSH in conventionally raised mice resulted in significant reduction of host weight-gain, plasma cholesterol and liver triglycerides. We demonstrate that bacterial BSH activity significantly impacts systemic metabolic processes and adiposity in the host, and represents a key mechanistic target for the control of obesity and hypercholesterolaemia. Germ free Swiss Webster mice were monocolonised with EC containing the bacterial gene, Bile salt hydroalse. The treatment groups and relevant controls were; 1. Germ Free(GF) n=4 , 2. GF and EC n=4, 3. GF and EC +BSH1 n=4, 4. GF and EC+ BSH2 n=4, 5. GF re-conventionalised (CONV-D) n= 5. The Ileum and Liver were removed and the RNA extracted (RNAeasy plus universal kit (Qiagen), quantified and Microarrays were carried out using mouse Exon ST1.0 arrays (Affymetrix) by Almac Group, Craigavon, Northern Ireland. Analysis and pathway mapping was carried out by ALMAC and using Subio Platform software (Subio Inc) and Genesis Software.

ORGANISM(S): Mus musculus

SUBMITTER: John Mac Sharry 

PROVIDER: E-GEOD-46952 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Regulation of host weight gain and lipid metabolism by bacterial bile acid modification in the gut.

Joyce Susan A SA   MacSharry John J   Casey Patrick G PG   Kinsella Michael M   Murphy Eileen F EF   Shanahan Fergus F   Hill Colin C   Gahan Cormac G M CG  

Proceedings of the National Academy of Sciences of the United States of America 20140505 20


Alterations in the gastrointestinal microbiota have been implicated in obesity in mice and humans, but the key microbial functions influencing host energy metabolism and adiposity remain to be determined. Despite an increased understanding of the genetic content of the gastrointestinal microbiome, functional analyses of common microbial gene sets are required. We established a controlled expression system for the parallel functional analysis of microbial alleles in the murine gut. Using this app  ...[more]

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