C URRENT OPINION Bile acids and the gut microbiome

Purpose of review We examine the latest research on the emerging bile acid-gut microbiome axis and its role in health and disease. Our focus revolves around two key microbial pathways for degrading bile salts, and the impact of bile acid composition in the gut on the gut microbiome and host physiology. Recent findings Bile acid pool size has recently been shown to be a function of microbial metabolism of bile acids in the intestines. Recent studies have shown potential mechanisms explaining how perturbations in the microbiome affect bile acid pool size and composition. Bile acids are emerging as regulators of the gut microbiome at the highest taxonomic levels. The role of bile acids as hormones and potentiators of liver cancer is also emerging. Summary The host and microbiome appear to regulate bile acid pool size. The host produces a large, conjugated hydrophilic bile acid pool, maintained through positive-feedback antagonism of farnesoid X receptor (FXR) in intestine and liver. Members of the microbiome utilize bile acids and their conjugates resulting in agonism of FXR in intestine and liver resulting in a smaller, unconjugated hydrophobic bile acid pool. Hydrophilicity of the bile acid pool is associated with disease states. Reduced bile acid levels in the gut are associated with bacterial overgrowth and inflammation. Diet, antibiotic therapy, and disease states affect the balance of the microbiome-bile acid pool.

[1]  Andmorgan R. Fisher,et al.  Altered profile of human gut microbiome is associated with cirrhosis and its complications. , 2014, Journal of hepatology.

[2]  M. Rudling,et al.  Muricholic bile acids are potent regulators of bile acid synthesis via a positive feedback mechanism , 2014, Journal of internal medicine.

[3]  James B. Mitchell,et al.  Microbiome remodelling leads to inhibition of intestinal farnesoid X receptor signalling and decreased obesity , 2013, Nature Communications.

[4]  J. Alves,et al.  Cirrhosis, bile acids and gut microbiota , 2013, Gut microbes.

[5]  Masahira Hattori,et al.  Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome , 2013, Nature.

[6]  H. Nittono,et al.  Modulation of the fecal bile acid profile by gut microbiota in cirrhosis. , 2013, Journal of Hepatology.

[7]  F. Bäckhed,et al.  Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. , 2013, Cell metabolism.

[8]  N. Pavlović,et al.  Probiotics—Interactions with Bile Acids and Impact on Cholesterol Metabolism , 2012, Applied Biochemistry and Biotechnology.

[9]  Masoumeh Sikaroodi,et al.  Colonic mucosal microbiome differs from stool microbiome in cirrhosis and hepatic encephalopathy and is linked to cognition and inflammation. , 2012, American journal of physiology. Gastrointestinal and liver physiology.

[10]  Yunwei Wang,et al.  Dietary fat-induced taurocholic acid production promotes pathobiont and colitis in IL-10−/− mice , 2012, Nature.

[11]  S. Spiegel,et al.  Conjugated bile acids activate the sphingosine‐1‐phosphate receptor 2 in primary rodent hepatocytes , 2012, Hepatology.

[12]  P. Hylemon,et al.  Linkage of gut microbiome with cognition in hepatic encephalopathy. , 2012, American journal of physiology. Gastrointestinal and liver physiology.

[13]  Association between the ABO blood group and the human intestinal microbiota composition , 2012, BMC Microbiology.

[14]  V. DelVecchio,et al.  Brucella abortus Choloylglycine Hydrolase Affects Cell Envelope Composition and Host Cell Internalization , 2011, PloS one.

[15]  Tetsuya Hayashi,et al.  Bile acid is a host factor that regulates the composition of the cecal microbiota in rats. , 2011, Gastroenterology.

[16]  J. Raufman,et al.  Bile Acids Regulate Cardiovascular Function , 2011, Clinical and translational science.

[17]  E. Want,et al.  Systemic gut microbial modulation of bile acid metabolism in host tissue compartments , 2010, Proceedings of the National Academy of Sciences.

[18]  V. Keitel,et al.  Bile Acid-Induced Arrhythmia Is Mediated by Muscarinic M2 Receptors in Neonatal Rat Cardiomyocytes , 2010, PloS one.

[19]  P. Dent,et al.  Bile acids as regulatory molecules , 2009, Journal of Lipid Research.

[20]  T. Miloh,et al.  beta-Klotho and FGF-15/19 inhibit the apical sodium-dependent bile acid transporter in enterocytes and cholangiocytes. , 2008, American journal of physiology. Gastrointestinal and liver physiology.

[21]  S. Kliewer,et al.  Differential regulation of bile acid homeostasis by the farnesoid X receptor in liver and intestine Published, JLR Papers in Press, August 24, 2007. , 2007, Journal of Lipid Research.

[22]  S. Kliewer,et al.  Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[23]  R. Ley,et al.  Ecological and Evolutionary Forces Shaping Microbial Diversity in the Human Intestine , 2006, Cell.

[24]  Dae-Joong Kang,et al.  Bile salt biotransformations by human intestinal bacteria Published, JLR Papers in Press, November 18, 2005. , 2006, Journal of Lipid Research.

[25]  J. Auwerx,et al.  Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation , 2006, Nature.

[26]  S. Kliewer,et al.  Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis. , 2005, Cell metabolism.

[27]  C. Hill,et al.  The interaction between bacteria and bile. , 2005, FEMS microbiology reviews.

[28]  W. Scheppach,et al.  Antagonistic effects of sulfide and butyrate on proliferation of colonic mucosa , 1996, Digestive Diseases and Sciences.

[29]  H. Bernstein,et al.  Bile acids as carcinogens in human gastrointestinal cancers. , 2005, Mutation research.

[30]  J. Raufman,et al.  REVIEW: Activation of Muscarinic Receptor Signaling by Bile Acids: Physiological and Medical Implications , 2003, Digestive Diseases and Sciences.

[31]  Masataka Harada,et al.  A G Protein-coupled Receptor Responsive to Bile Acids* , 2003, The Journal of Biological Chemistry.

[32]  M. Haussler,et al.  Vitamin D Receptor As an Intestinal Bile Acid Sensor , 2002, Science.

[33]  Masahiro Tohkin,et al.  Targeted Disruption of the Nuclear Receptor FXR/BAR Impairs Bile Acid and Lipid Homeostasis , 2000, Cell.

[34]  J. Raufman,et al.  Lithocholyltaurine interacts with cholinergic receptors on dispersed chief cells from guinea pig stomach. , 1998, American journal of physiology. Gastrointestinal and liver physiology.

[35]  H. Laue,et al.  Taurine reduction in anaerobic respiration of Bilophila wadsworthia RZATAU , 1997, Applied and environmental microbiology.

[36]  Assessment of fecal bacteria with bile acid 7 alpha-dehydroxylating activity for the presence of bai-like genes. , 1997, Applied and environmental microbiology.

[37]  W. Hardison Hepatic taurine concentration and dietary taurine as regulators of bile acid conjugation with taurine. , 1978, Gastroenterology.