Microbiota Modification with Probiotics Induces Hepatic Bile Acid Synthesis via Downregulation of the Fxr-Fgf15 Axis in Mice

• DOI: 10.1016/j.celrep.2014.02.032
• Publication Date: 2014-03-22T04:47:57Z
• Authors: Chiara Degirolamo; Stefania Rainaldi; Fabiola Bovenga; Stefania Murzilli; Antonio Moschetta
• Keywords: Farnesoid X receptor; Enterohepatic circulation; Chenodeoxycholic acid; Prebiotic; Dysbiosis

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 hydrophobicity, thus contributing to enterohepatic circulation. Microbiota-targeted therapies are now emerging as effective strategies for preventing and/or treating gut-related diseases. Here, we show that gut modulation induced VSL#3 probiotics enhances deconjugation fecal excretion in mice. These events associated with changes ileal absorption, repression of the farnesoid X receptor-fibroblast growth factor 15 (FXR-FGF15) axis, increased hepatic neosynthesis. Treatment a FXR agonist normalized levels probiotic-administered mice, whereas probiotic-induced alterations metabolism abolished upon FGF15 deficiency. Our data provide clear vivo evidence promote subsequent induce neosynthesis via downregulation gut-liver FXR-FGF15 axis.