title: Microbiota modification with probiotics induces hepatic bile acid synthesis via downregulation of the Fxr-Fgf15 axis in mice.
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 in vivo 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.
authors.affiliation: National Cancer Research Center, IRCCS Istituto Oncologico "Giovanni Paolo II," Bari 70124, Italy; Fondazione Mario Negri Sud, Santa Maria Imbaro, 66030 Chieti, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Degirolamo
authors.affiliation: Fondazione Mario Negri Sud, Santa Maria Imbaro, 66030 Chieti, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Rainaldi
authors.affiliation: National Cancer Research Center, IRCCS Istituto Oncologico "Giovanni Paolo II," Bari 70124, Italy; Fondazione Mario Negri Sud, Santa Maria Imbaro, 66030 Chieti, Italy.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Bovenga
authors.affiliation: Fondazione Mario Negri Sud, Santa Maria Imbaro, 66030 Chieti, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Murzilli
authors.affiliation: National Cancer Research Center, IRCCS Istituto Oncologico "Giovanni Paolo II," Bari 70124, Italy; Department of Interdisciplinary Medicine, "Aldo Moro" University of Bari, Bari 70124, Italy. Electronic address: a.moschetta@oncologico.bari.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Moschetta
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000096:biosynthesis* / Q000378:metabolism; D015536:Down-Regulation; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects / Q000382:microbiology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000187:drug effects*; D019936:Probiotics / Q000494:pharmacology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D015398:Signal Transduction; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D001647:Bile Acids and Salts; D005346:Fibroblast Growth Factors; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated; C108526:fibroblast growth factor 15, mouse