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Bazedoxifene and conjugated estrogen combination improves gut-liver axis health

ABSTRACT: Bazedoxifene and conjugated estrogen combination improves gut-liver axis health

PROVIDER: PRJNA360113 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR5133590.fastq.gz	Fastqsanger.gz
	SRR5133581.fastq.gz	Fastqsanger.gz
	SRR5133591.fastq.gz	Fastqsanger.gz
	SRR5133582.fastq.gz	Fastqsanger.gz
	SRR5133592.fastq.gz	Fastqsanger.gz

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Bazedoxifene and conjugated estrogen combination improves gut-liver axis health [microbiota]

Project description:Bazedoxifene and conjugated estrogens (CE+BZA) combination has been shown to prevent visceral adiposity and weight gain after menopause. However, its interaction with the microbiota has yet to be examined. In the present study, we use several –omics technologies to characterize the effects of various estrogens on the health of gut-liver axis. As reported in previous studies, CE+BZA combination is very effective at preventing ovariectomy-induced weight gain in mice fed a high-fat diet. Additionally, CE+BZA induces unique liver transcriptomic and blood metabolite profiles compared to estradiol, conjugated estrogens alone, and bazedoxifene alone. Several pathways and metabolites influenced are associated with lower rates of inflammation and overall benefits to gut and liver health. Finally, microbiome analysis shows that several bacterial species that potentially metabolize estrogens and affect their half-life in the body were significantly changed in CE+BZA treated mice. Our findings indicate a possible link between certain estrogens and gut microbiome and suggest a metabolic benefit of estrogens through manipulation of the gut-liver axis.

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Project description:The bazedoxifene and conjugated estrogens (CE+BZA) combination has been shown to prevent visceral adiposity and weight gain after ovariectomy. However, its impact on the liver transcriptomes associated with prevention of hepatosteatosis is yet to be determined. In the present study, we use liver transcriptomics and plasma metabolomics analysis to characterize the effects of various estrogens on liver. The CE+BZA combination was very effective at preventing ovariectomy-induced weight gain in mice fed a high-fat diet (HFD). In CE+BZA treated animals, liver weight and hepatic lipid deposition were significantly lower than in Vehicle (Veh) treated animals. Additionally, CE+BZA induced unique liver transcriptome and plasma metabolome profiles compared to estradiol, conjugated estrogens alone, and bazedoxifene alone. Blood plasma metabolite analysis identified several metabolites similar to and distinct from other estrogen treatments. Integrated pathway analysis showed that gene networks that were associated with inflammation, reactive oxygen species pathway and lipid metabolism and their relevant metabolites were regulated significantly by CE+BZA treatment. Thus, long-term CE+BZA treatment modulated hepatic metabolic gene networks and their associated metabolites and improves hepatic health without stimulating the uterus.

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