Microbiota modification with probiotics induces hepatic bile acid synthesis via downregulation of the Fxr-Fgf15 axis in mice

Chiara Degirolamo, Stefania Rainaldi, Fabiola Bovenga, Stefania Murzilli, Antonio Moschetta

Research output: Contribution to journalArticle

123 Citations (Scopus)

Abstract

Gut microbiota influences host health status by providing trophic, protective, and metabolic functions, including bile acid (BA) biotransformation. Microbial imprinting on BA signature modifies pool size and hydrophobicity, thus contributing to BA enterohepatic circulation. Microbiota-targeted therapies are now emerging as effective strategies for preventing and/or treating gut-related diseases. Here, we show that gut microbiota modulation induced by VSL#3 probiotics enhances BA deconjugation and fecal excretion in mice. These events are associated with changes in ileal BA absorption, repression of the enterohepatic farnesoid X receptor-fibroblast growth factor 15 (FXR-FGF15) axis, and increased hepatic BA neosynthesis. Treatment with a FXR agonist normalized fecal BA levels in probiotic-administered mice, whereas probiotic-induced alterations in BA metabolism are abolished upon FXR and FGF15 deficiency. Our data provide clear invivo evidence that VSL#3 probiotics promote ileal BA deconjugation with subsequent fecal BA excretion and induce hepatic BA neosynthesis via downregulation of the gut-liver FXR-FGF15 axis.

Original languageEnglish (US)
Pages (from-to)12-18
Number of pages7
JournalCell Reports
Volume7
Issue number1
DOIs
StatePublished - Oct 4 2014

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Microbiota
Probiotics
Bile Acids and Salts
Down-Regulation
Liver
Fibroblast Growth Factor Receptors
Enterohepatic Circulation
Fibroblast Growth Factors
Hydrophobicity
Biotransformation
Hydrophobic and Hydrophilic Interactions
Metabolism
Health Status
Modulation
Health

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Microbiota modification with probiotics induces hepatic bile acid synthesis via downregulation of the Fxr-Fgf15 axis in mice. / Degirolamo, Chiara; Rainaldi, Stefania; Bovenga, Fabiola; Murzilli, Stefania; Moschetta, Antonio.

In: Cell Reports, Vol. 7, No. 1, 04.10.2014, p. 12-18.

Research output: Contribution to journalArticle

Degirolamo, Chiara ; Rainaldi, Stefania ; Bovenga, Fabiola ; Murzilli, Stefania ; Moschetta, Antonio. / Microbiota modification with probiotics induces hepatic bile acid synthesis via downregulation of the Fxr-Fgf15 axis in mice. In: Cell Reports. 2014 ; Vol. 7, No. 1. pp. 12-18.
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