title: The human gut sterolbiome: bile acid-microbiome endocrine aspects and therapeutics.
abstract: The human body is now viewed as a complex ecosystem that on a cellular and gene level is mainly prokaryotic. The mammalian liver synthesizes and secretes hydrophilic primary bile acids, some of which enter the colon during the enterohepatic circulation, and are converted into numerous hydrophobic metabolites which are capable of entering the portal circulation, returned to the liver, and in humans, accumulating in the biliary pool. Bile acids are hormones that regulate their own synthesis, transport, in addition to glucose and lipid homeostasis, and energy balance. The gut microbial community through their capacity to produce bile acid metabolites distinct from the liver can be thought of as an "endocrine organ" with potential to alter host physiology, perhaps to their own favor. We propose the term "sterolbiome" to describe the genetic potential of the gut microbiome to produce endocrine molecules from endogenous and exogenous steroids in the mammalian gut. The affinity of secondary bile acid metabolites to host nuclear receptors is described, the potential of secondary bile acids to promote tumors, and the potential of bile acids to serve as therapeutic agents are discussed.
authors.affiliation: Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298, USA ; McGuire VA Medical Center, Richmond, VA 23249, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Ridlon
authors.affiliation: McGuire VA Medical Center, Richmond, VA 23249, USA ; Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Jasmohan S
authors.initials: JS
authors.lastname: Bajaj
keywords: APC, adenomatous polyposis coli; BA, bile acids; BSH, bile salt hydrolases; Bile acids; CA, cholic acid; CDCA, chenodeoxycholic acid; COX-2, cyclooxygenase-2; CRC, colorectal cancer; CYP27A1, sterol-27-hydroxylase; CYP7A1, cholesterol 7α-hydroxylase; CYP8B1, sterol 12α-hydroxylase; DCA, deoxycholic acid; EGFR, epidermal growth factor receptor; FAP, familial adenomatous polyposis; FGF15/19, fibroblast growth factor 15/19; FXR, farnesoid X receptor; GABA, γ-aminobutyric acid; GPCR, G-protein coupled receptors; Gut microbiome; HMP, Human Microbiome Project; HSDH, hydroxysteroid dehydrogenase; LCA, lithocholic acid; LOX, lipooxygenase; MetaHIT, Metagenomics of the Human Intestinal Tract; Metabolite; NSAIDs, non-steroidal anti-inflammatory drugs; PKC, protein kinase C; PSC, primary sclerosing cholangitis; PXR, pregnane X receptor; Sterolbiome; Therapeutic agent; UDCA, ursodeoxycholic acid; VDR, vitamin D receptor