FXR-Dependent Modulation of the Human Small Intestinal Microbiome by the Bile Acid Derivative Obeticholic Acid

Gastroenterology

Volumn 155, Issue 6, 2018, Pages 1741-1752.e5

  Friedman, Elliot S ^a   Li, Yun ^a   Shen, Ting Chin David ^a   Jiang, Jack ^a   Chau, Lillian ^a   Adorini, Luciano ^b   Babakhani, Farah ^b   Edwards, Jeffrey ^b   Shapiro, David ^b   Zhao, Chunyu ^c   Carr, Rotonya M ^a   Bittinger, Kyle ^c   Li, Hongzhe ^a   Wu, Gary D ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b INTERCEPT PHARMACEUTICALS   (United States)

^c CHILDREN S HOSPITAL OF PHILADELPHIA   (United States)

Author keywords

Gene Regulation; Genetics; Metabolism; Nuclear Hormone Receptor

Indexed keywords

FARNESOID X RECEPTOR; GLYCOCHENODEOXYCHOLIC ACID; GLYCOCHOLIC ACID; OBETICHOLIC ACID; BILE ACID; CELL RECEPTOR; CHENODEOXYCHOLIC ACID; FARNESOID X-ACTIVATED RECEPTOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BACTERIAL GENOME; BILE ACID SYNTHESIS; CONTROLLED STUDY; DNA SYNTHESIS; FEMALE; GENE SEQUENCE; HUMAN; HUMAN EXPERIMENT; INTESTINE FLORA; MALE; METAGENOMICS; MINIMUM INHIBITORY CONCENTRATION; MOUSE; MOUTH FLORA; MULTIPLE DRUG DOSE; NONHUMAN; NORMAL HUMAN; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; STREPTOCOCCUS THERMOPHILUS; ADULT; ANALOGS AND DERIVATIVES; ANIMAL; C57BL MOUSE; CLINICAL TRIAL; DRUG EFFECT; MICROBIOLOGY; PHYSIOLOGY; SMALL INTESTINE;

ADULT; ANIMALS; BILE ACIDS AND SALTS; CHENODEOXYCHOLIC ACID; FEMALE; GASTROINTESTINAL MICROBIOME; HEALTHY VOLUNTEERS; HUMANS; INTESTINE, SMALL; MALE; MICE; MICE, INBRED C57BL; RECEPTORS, CYTOPLASMIC AND NUCLEAR;

EID: 85057564693     PISSN: 00165085     EISSN: 15280012     Source Type: Journal    
DOI: 10.1053/j.gastro.2018.08.022     Document Type: Article

References (38)

1. Derrien, M., van Hylckama Vlieg, J.E., Fate, activity, and impact of ingested bacteria within the human gut microbiota. Trends Microbiol 23 (2015), 354–366.
2. van den Bogert, B., Erkus, O., Boekhorst, J., et al. Diversity of human small intestinal Streptococcus and Veillonella populations. FEMS Microbiol Ecol 85 (2013), 376–388.
3. Charlson, E.S., Bittinger, K., Haas, A.R., et al. Topographical continuity of bacterial populations in the healthy human respiratory tract. Am J Respir Crit Care Med 184 (2011), 957–963.
4. Schneider, K.M., Albers, S., Trautwein, C., Role of bile acids in the gut–liver axis. J Hepatol 68 (2018), 1083–1085.
5. Carr, R.M., Reid, A.E., FXR agonists as therapeutic agents for non-alcoholic fatty liver disease. Curr Atheroscler Rep, 17, 2015, 500.
6. Begley, M., Gahan, C.G.M., Hill, C., The interaction between bacteria and bile. FEMS Microbiol Rev 29 (2005), 625–651.
7. Ni, J., Shen, T.D., Chen, E.Z., et al. A role for bacterial urease in gut dysbiosis and Crohn's disease. Sci Transl Med, 9, 2017.
8. Lewis, J.D., Chen, E.Z., Baldassano, R.N., et al. Inflammation, antibiotics, and diet as environmental stressors of the gut microbiome in pediatric Crohn's disease. Cell Host Microbe 18 (2015), 489–500.
9. Engelkirk, P.G., Duben-Engelkirk, J.L., Laboratory diagnosis of infectious diseases: essentials of diagnostic microbiology. 2008, Lippincott Williams & Wilkins, Baltimore.
10. Galman, C., Arvidsson, I., Angelin, B., et al. Monitoring hepatic cholesterol 7alpha-hydroxylase activity by assay of the stable bile acid intermediate 7alpha-hydroxy-4-cholesten-3-one in peripheral blood. J Lipid Res 44 (2003), 859–866.
11. Hirschfield, G.M., Mason, A., Luketic, V., et al. Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid. Gastroenterology 148 (2015), 751–761 e8.
12. Aziz, R.K., Breitbart, M., Edwards, R.A., Transposases are the most abundant, most ubiquitous genes in nature. Nucleic Acids Res 38 (2010), 4207–4217.
13. He, G., Shankar, R.A., Chzhan, M., et al. Noninvasive measurement of anatomic structure and intraluminal oxygenation in the gastrointestinal tract of living mice with spatial and spectral EPR imaging. Proc Natl Acad Sci U S A 96 (1999), 4586–4591.
14. Northfield, T.C., McColl, I., Postprandial concentrations of free and conjugated bile acids down the length of the normal human small intestine. Gut 14 (1973), 513–518.
15. Zhang, Y., LaCerte, C., Kansra, S., et al. Comparative potency of obeticholic acid and natural bile acids on FXR in hepatic and intestinal in vitro cell models. Pharmacol Res Perspect, 5, 2017.
16. Verbeke, L., Farre, R., Verbinnen, B., et al. The FXR agonist obeticholic acid prevents gut barrier dysfunction and bacterial translocation in cholestatic rats. Am J Pathol 185 (2015), 409–419.
17. Cox, L.M., Cho, I., Young, S.A., et al. The nonfermentable dietary fiber hydroxypropyl methylcellulose modulates intestinal microbiota. FASEB J 27 (2013), 692–702.
18. Klaassen, C.D., Cui, J.Y., Review: mechanisms of how the intestinal microbiota alters the effects of drugs and bile acids. Drug Metab Dispos 43 (2015), 1505–1521.
19. Zeevi, D., Korem, T., Zmora, N., et al. Personalized nutrition by prediction of glycemic responses. Cell 163 (2015), 1079–1094.
20. Buffie, C.G., Bucci, V., Stein, R.R., et al. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature 517 (2015), 205–208.
21. Loomba, R., Seguritan, V., Li, W., et al. Gut microbiome-based metagenomic signature for non-invasive detection of advanced fibrosis in human nonalcoholic fatty liver disease. Cell Metab 25 (2017), 1054–1062 e5.
22. Barber, G.E., Yajnik, V., Khalili, H., et al. Genetic markers predict primary non-response and durable response to anti-TNF biologic therapies in Crohn's disease. Am J Gastroenterol 111 (2016), 1816–1822.
23. Bouhnik, Y., Alain, S., Attar, A., et al. Bacterial populations contaminating the upper gut in patients with small intestinal bacterial overgrowth syndrome. Am J Gastroenterol 94 (1999), 1327–1331.
24. Qin, N., Yang, F., Li, A., et al. Alterations of the human gut microbiome in liver cirrhosis. Nature 513 (2014), 59–64.
25. Ubeda, M., Lario, M., Munoz, L., et al. Obeticholic acid reduces bacterial translocation and inhibits intestinal inflammation in cirrhotic rats. J Hepatol 64 (2016), 1049–1057.
26. Islam, K.B., Fukiya, S., Hagio, M., et al. Bile acid is a host factor that regulates the composition of the cecal microbiota in rats. Gastroenterology 141 (2011), 1773–1781.
27. Forslund, K., Hildebrand, F., Nielsen, T., et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature 528 (2015), 262–266.
28. Shen, T.D., Pyrsopoulos, N., Rustgi, V.K., Microbiota and the liver. Liver Transpl 24 (2018), 539–550.
29. Flach, J., van der Waal, M.B., Kardinaal, A.F.M., et al. Probiotic research priorities for the healthy adult population: a review on the health benefits of Lactobacillus rhamnosus GG and Bifidobacterium animalis subspecies lactis BB-12. Cogent Food Agriculture, 4, 2018.
30. Shen, T., Albenberg, L., Bittinger, K., et al. Engineering the gut microbiota to treat hyperammonemia. J Clin Invest 125 (2015), 2841–2850.
31. Caporaso, J.G., Kuczynski, J., Stombaugh, J., et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods 7 (2010), 335–336.
32. Edgar, R.C., Search and clustering orders of magnitude faster than BLAST. Bioinformatics 26 (2010), 2460–2461.
33. Benjamini, Y., Hochberg, Y., Controlling the false discovery rate—a practical and powerful approach to multiple testing. J R Stat Soc Series B Methodol 57 (1995), 289–300.
34. Bolger, A.M., Lohse, M., Usadel, B., Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30 (2014), 2114–2120.
35. Langmead, B., Salzberg, S.L., Fast gapped-read alignment with Bowtie 2. Nat Methods 9 (2012), 357–359.
36. Segata, N., Waldron, L., Ballarini, A., et al. Metagenomic microbial community profiling using unique clade-specific marker genes. Nat Methods 9 (2012), 811–814.
37. Abubucker, S., Segata, N., Goll, J., et al. Metabolic reconstruction for metagenomic data and its application to the human microbiome. PLoS Comput Biol, 8, 2012, e1002358.
38. Caspi, R., Billington, R., Ferrer, L., et al. The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of pathway/genome databases. Nucleic Acids Res 44 (2016), D471–D880.