Gut microbiota-related bile acid metabolism-FXR/TGR5 axis impacts the response to anti-α4β7-integrin therapy in humanized mice with colitis

References

• Chang JT, Longo DL. Pathophysiology of inflammatory bowel diseases. N Engl J Med. 2020;383(27):2652–23. doi:10.1056/NEJMra2002697.
   PubMed Web of Science ®Google Scholar
• Ananthakrishnan AN. Epidemiology and risk factors for IBD. Nat Rev Gastroenterol Hepatol. 2015;12:205–217. doi:10.1038/nrgastro.2015.34.
   PubMed Web of Science ®Google Scholar
• Knights D, Lassen KG, Xavier RJ. Advances in inflammatory bowel disease pathogenesis: linking host genetics and the microbiome. Gut. 2013;62:1505–1510. doi:10.1136/gutjnl-2012-303954.
   PubMed Web of Science ®Google Scholar
• Tysk C, Lindberg E, Järnerot G, Flodérus-Myrhed B. Ulcerative colitis and Crohn’s disease in an unselected population of monozygotic and dizygotic twins. A study of heritability and the influence of smoking. Gut. 1988;29:990–996. doi:10.1136/gut.29.7.990.
   PubMed Web of Science ®Google Scholar
• Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, Hui KY, Lee JC, Schumm LP, Sharma Y, Anderson CA, et al. Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature. 2012;491(7422):119–124. doi:10.1038/nature11582.
   PubMed Web of Science ®Google Scholar
• Liu JZ, van Sommeren S, Huang H, Ng SC, Alberts R, Takahashi A, Ripke S, Lee JC, Jostins L, Shah T, et al. Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations. Nat Genet. 2015;47:979–986. doi:10.1038/ng.3359.
   PubMed Web of Science ®Google Scholar
• Olivera P, Danese S, Peyrin-Biroulet L. Next generation of small molecules in inflammatory bowel disease. Gut. 2017;66(2):199–209. doi:10.1136/gutjnl-2016-312912.
   PubMed Web of Science ®Google Scholar
• Danese S, Vuitton L, Peyrin-Biroulet L. Biologic agents for IBD: practical insights. Nat Rev Gastroenterol Hepatol. 2015;12(9):537–545. doi:10.1038/nrgastro.2015.135.
   PubMed Web of Science ®Google Scholar
• Peyrin-Biroulet L, Reinisch W, Colombel J, Mantzaris G, Kornbluth A, Diamond R, Rutgeerts P, Tang L, Cornillie F, Sandborn W. Clinical disease activity, C-reactive protein normalisation and mucosal healing in Crohn’s disease in the SONIC trial. Gut. 2014;63:88‐95. doi:10.1136/gutjnl-2013-304984.
   Web of Science ®Google Scholar
• Ben-Horin S, Kopylov U, Chowers Y. Optimizing anti-TNF treatments in inflammatory bowel disease. Autoimmun Rev. 2014;13(1):24–30. doi:10.1016/j.autrev.2013.06.002.
   PubMed Web of Science ®Google Scholar
• Boyapati RK, Kalla R, Satsangi J, Ho GT. Biomarkers in search of precision medicine in IBD. Am J Gastroenterol. 2016;111(12):1682–1690. doi:10.1038/ajg.2016.441.
   PubMed Web of Science ®Google Scholar
• West NR, Hegazy AN, Owens BMJ, Bullers SJ, Linggi B, Buonocore S, Coccia M, Gortz D, This S, Stockenhuber K, et al. Oncostatin M drives intestinal inflammation and predicts response to tumor necrosis factor–neutralizing therapy in patients with inflammatory bowel disease. Nat Med. 2017;23(5):579–589. doi:10.1038/nm.4307.
   PubMed Web of Science ®Google Scholar
• Verstockt B, Verstockt S, Creyns B, Tops S, Van Assche G, Gils A, Ceuppens JL, Vermeire S, Ferrante M, Breynaert C. Mucosal IL13RA2 expression predicts nonresponse to anti-TNF therapy in Crohn’s disease. Aliment Pharmacol Ther. 2019;49(5):572–581. doi:10.1111/apt.15126.
   PubMed Web of Science ®Google Scholar
• Gaujoux R, Starosvetsky E, Maimon N, Vallania F, Bar-Yoseph H, Pressman S, Weisshof R, Goren I, Rabinowitz K, Waterman M, et al. Cell-centred meta-analysis reveals baseline predictors of anti-TNFα non-response in biopsy and blood of patients with IBD. Gut. 2019;68(4):604–614. doi:10.1136/gutjnl-2017-315494.
   PubMed Web of Science ®Google Scholar
• Veny M, Fernández-Clotet A, Panés J. Controlling leukocyte trafficking in IBD. Pharmacol Res. 2020;159:105050. doi:10.1016/j.phrs.2020.105050.
   PubMed Web of Science ®Google Scholar
• Kobayashi T, Hibi T. Improving IBD outcomes in the era of many treatment options. Nat Rev Gastroenterol Hepatol. 2023;20(2):79–80. doi:10.1038/s41575-022-00738-z.
   PubMed Web of Science ®Google Scholar
• Wyant T, Fedyk E, Abhyankar B. An overview of the mechanism of action of the monoclonal antibody vedolizumab. J Crohns Colitis. 2016;10(12):1437–1444. doi:10.1093/ecco-jcc/jjw092.
   PubMed Web of Science ®Google Scholar
• Sands B, Peyrin-Biroulet L, Loftus E, Danese S, Colombel J, Törüner M, Jonaitis L, Abhyankar B, Chen J, Rogers R, et al. Vedolizumab versus adalimumab for moderate-to-severe ulcerative colitis. N Engl J Med. 2019;381(13):1215–1226. doi:10.1056/NEJMra1905725.
   PubMed Web of Science ®Google Scholar
• Becker C, Neurath MF, Wirtz S. The Intestinal microbiota in inflammatory bowel disease. Ilar J. 2015;56(2):192–204. doi:10.1093/ilar/ilv030.
   PubMed Web of Science ®Google Scholar
• Forbes JD, Van Domselaar G, Bernstein CN. The gut microbiota in immune-mediated inflammatory diseases. Front Microbiol. 2016;7:1081. doi:10.3389/fmicb.2016.01081.
   PubMed Web of Science ®Google Scholar
• Kostic AD, Xavier RJ, Gevers D. The microbiome in inflammatory bowel disease: current status and the future ahead. Gastroenterology. 2014;146(6):1489–1499. doi:10.1053/j.gastro.2014.02.009.
   PubMed Web of Science ®Google Scholar
• Ananthakrishnan AN, Luo C, Yajnik V, Khalili H, Garber JJ, Stevens BW, Cleland T, Xavier RJ. Gut microbiome function predicts response to anti-integrin biologic therapy in inflammatory bowel diseases. Cell Host & Microbe. 2017;21(5):603–610.e3. doi:10.1016/j.chom.2017.04.010.
   PubMed Web of Science ®Google Scholar
• Franzosa EA, Sirota-Madi A, Avila-Pacheco J, Fornelos N, Haiser HJ, Reinker S, Vatanen T, Hall AB, Mallick H, McIver LJ, et al. Gut microbiome structure and metabolic activity in inflammatory bowel disease. Nature Microbiol. 2019;4(2):293–305. doi:10.1038/s41564-018-0306-4.
   PubMed Web of Science ®Google Scholar
• Jacobs JP, Goudarzi M, Singh N, Tong M, McHardy IH, Ruegger P, Asadourian M, Moon BH, Ayson A, Borneman J, et al. A disease-associated microbial and metabolomics state in relatives of pediatric inflammatory bowel disease patients. Cell Mol Gastroenterol Hepatol. 2016;2(6):750–766. doi:10.1016/j.jcmgh.2016.06.004.
   PubMed Web of Science ®Google Scholar
• Torres J, Palmela C, Brito H, Bao X, Ruiqi H, Moura-Santos P, Pereira da Silva J, Oliveira A, Vieira C, Perez K, et al. The gut microbiota, bile acids and their correlation in primary sclerosing cholangitis associated with inflammatory bowel disease. United European Gastroenterol J. 2018;6(1):112–122. doi:10.1177/2050640617708953.
   PubMed Web of Science ®Google Scholar
• Jones ML, Martoni CJ, Prakash S. Letter to the editor regarding the report of Duboc et al: Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel disease. Gut. 2013;62:654–655. doi:10.1136/gutjnl-2012-303867.
   PubMed Web of Science ®Google Scholar
• Chiang JY. Bile acids: regulation of synthesis. J Lipid Res. 2009;50(10):1955–1966. doi:10.1194/jlr.R900010-JLR200.
   PubMed Web of Science ®Google Scholar
• Fiorucci S, Carino A, Baldoni M, Santucci L, Costanzi E, Graziosi L, Distrutti E, Biagioli M. Bile acid signaling in inflammatory bowel diseases. Dig Dis Sci. 2021;66(3):674–693. doi:10.1007/s10620-020-06715-3.
   PubMed Web of Science ®Google Scholar
• Paramsothy S, Nielsen S, Kamm MA, Deshpande NP, Faith JJ, Clemente JC, Paramsothy R, Walsh AJ, van den Bogaerde J, Samuel D, et al. Specific bacteria and metabolites associated with response to fecal microbiota transplantation in patients with ulcerative colitis. Gastroenterology. 2019;156(5):1440–1454.e2. doi:10.1053/j.gastro.2018.12.001.
   PubMed Web of Science ®Google Scholar
• Sorrentino G, Perino A, Yildiz E, El Alam G, Bou Sleiman M, Gioiello A, Pellicciari R, Schoonjans K. Bile acids signal via TGR5 to activate intestinal stem cells and epithelial regeneration. Gastroenterology. 2020;159(3):956–968.e8. doi:10.1053/j.gastro.2020.05.067.
   PubMed Web of Science ®Google Scholar
• Cipriani S, Mencarelli A, Chini MG, Distrutti E, Renga B, Bifulco G, Baldelli F, Donini A, Fiorucci S. The bile acid receptor GPBAR-1 (TGR5) modulates integrity of intestinal barrier and immune response to experimental colitis. PLoS One. 2011;6(10):e25637. doi:10.1371/journal.pone.0025637.
   PubMed Web of Science ®Google Scholar
• Gadaleta RM, van Erpecum KJ, Oldenburg B, Willemsen EC, Renooij W, Murzilli S, Klomp LW, Siersema PD, Schipper ME, Danese S, et al. Farnesoid X receptor activation inhibits inflammation and preserves the intestinal barrier in inflammatory bowel disease. Gut. 2011;60(4):463–472. doi:10.1136/gut.2010.212159.
   PubMed Web of Science ®Google Scholar
• Billerbeck E, Barry WT, Mu K, Dorner M, Rice CM, Ploss A. Development of human CD4+FoxP3+ regulatory T cells in human stem cell factor–, granulocyte-macrophage colony-stimulating factor–, and interleukin-3–expressing NOD-SCID IL2Rγnull humanized mice. Blood. 2011;117(11):3076–3086. doi:10.1182/blood-2010-08-301507.
   PubMed Web of Science ®Google Scholar
• Wirtz S, Popp V, Kindermann M, Gerlach K, Weigmann B, Fichtner-Feigl S, Neurath MF. Chemically induced mouse models of acute and chronic intestinal inflammation. Nat Protoc. 2017;12(7):1295–1309. doi:10.1038/nprot.2017.044.
   PubMed Web of Science ®Google Scholar
• Manzini R, Schwarzfischer M, Atrott K, Laimbacher A, Lang S, Wawrzyniak M, Rickenbacher A, Turina M, Hruz P, Lissner D, et al. Combination of vedolizumab with tacrolimus is more efficient than vedolizumab alone in the treatment of experimental colitis. Inflamm Bowel Dis. 2021;27(12):1986–1998. doi:10.1093/ibd/izab063.
   PubMed Web of Science ®Google Scholar
• Hou Q, Huang J, Zhao L, Pan X, Liao C, Jiang Q, Lei J, Guo F, Cui J, Guo Y, et al. Dietary genistein increases microbiota-derived short chain fatty acid levels, modulates homeostasis of the aging gut, and extends healthspan and lifespan. Pharmacol Res. 2023;188:106676. doi:10.1016/j.phrs.2023.106676.
   PubMed Web of Science ®Google Scholar
• Jin JH, Xu Z, Zhang LN, Zhang C, Zhao XD, Mao YX, Zhang HJ, Liang XG, Wu JL, Yang Y, et al. Gut-derived β-amyloid: Likely a centerpiece of the gut–brain axis contributing to Alzheimer’s pathogenesis. Gut Microbes. 2023;15(1):2167172. doi:10.1080/19490976.2023.2167172.
   PubMed Web of Science ®Google Scholar
• Yousefi-Ahmadipour A, Rashidian A, Mirzaei MR, Farsinejad A, PourMohammadi-Nejad F, Ghazi-Khansari M, Ai J, Shirian S, Allahverdi A, Saremi J, et al. Combination therapy of mesenchymal stromal cells and sulfasalazine attenuates trinitrobenzene sulfonic acid induced colitis in the rat: the S1P pathway. J Cell Physiol. 2019;234(7):11078–11091. doi:10.1002/jcp.27944.
   PubMed Web of Science ®Google Scholar
• Millar AD, Rampton DS, Chander CL, Claxson AW, Blades S, Coumbe A, Panetta J, Morris CJ, Blake DR. Evaluating the antioxidant potential of new treatments for inflammatory bowel disease using a rat model of colitis. Gut. 1996;39(3):407–415. doi:10.1136/gut.39.3.407.
   PubMed Web of Science ®Google Scholar
• Kiesler P, Fuss IJ, Strober W. Experimental models of inflammatory bowel diseases. Cell Mol Gastroenterol Hepatol. 2015;1(2):154–170. doi:10.1016/j.jcmgh.2015.01.006.
   PubMed Web of Science ®Google Scholar
• Harvey RF, Bradsha JM. A simple index of Crohn’s-disease activity. The Lancet. 1980;315(8167):514. doi:10.1016/s0140-6736(80)92767-1.
   Google Scholar
• Chen G, Ran X, Li B, Li Y, He D, Huang B, Fu S, Liu J, Wang W. Sodium butyrate inhibits inflammation and maintains epithelium barrier integrity in a TNBS-induced inflammatory bowel disease mice model. EBioMedicine. 2018;30:317–325. doi:10.1016/j.ebiom.2018.03.030.
   PubMed Web of Science ®Google Scholar
• Segata N, Izard J, Waldron L, Gevers D, Miropolsky L, Garrett WS, Huttenhower C. Metagenomic biomarker discovery and explanation. Genome Biol. 2011;12:R60. doi:10.1186/gb-2011-12-6-r60.
   PubMed Web of Science ®Google Scholar
• Li Y, Dong JL, Xiao HW, Zhang SQ, Wang B, Cui M, Fan SJ. Gut commensal derived-valeric acid protects against radiation injuries. Gut Microbes. 2020;11(4):789–806. doi:10.1080/19490976.2019.1709387.
   PubMed Web of Science ®Google Scholar
• Wirtz S, Neufert C, Weigmann B, Neurath MF. Chemically induced mouse models of intestinal inflammation. Nat Protoc. 2007;2(3):541–546. doi:10.1038/nprot.2007.41.
   PubMed Web of Science ®Google Scholar
• Larabi AB, Hugo LPM, Bäumler AJ. Bile acids as modulators of gut microbiota composition and function. Gut Microbes. 2023;15(1):2172671. doi:10.1080/19490976.2023.2172671.
   PubMed Web of Science ®Google Scholar
• Wahlstrom A, Sayin SI, Marschall HU, Backhed F. Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism. Cell Metab. 2016;24:41–50. doi:10.1016/j.cmet.2016.05.005.
   PubMed Web of Science ®Google Scholar
• Zhou X, Cao L, Jiang C, Xie Y, Cheng X, Krausz KW, Qi Y, Sun L, Shah YM, Gonzalez FJ, et al. PPARα-UGT axis activation represses intestinal FXR-FGF15 feedback signalling and exacerbates experimental colitis. Nat Commun. 2014;5(1):4573. doi:10.1038/ncomms5573.
   PubMedGoogle Scholar
• Song M, Ye J, Zhang F, Su H, Yang X, He H, Liu F, Zhu X, Wang L, Gao P, et al. Chenodeoxycholic acid (CDCA) protects against the lipopolysaccharide-induced impairment of the intestinal epithelial barrier function via the FXR-MLCK pathway. J Agric Food Chem. 2019;67(32):8868–8874. doi:10.1021/acs.jafc.9b03173.
   PubMed Web of Science ®Google Scholar
• Li S, Qiu M, Kong Y, Zhao X, Choi HJ, Reich M, Bunkelman BH, Liu Q, Hu S, Han M, et al. Bile acid G protein-coupled membrane receptor TGR5 modulates aquaporin 2–mediated water homeostasis. J Am Soc Nephrol. 2018;29(11):2658–2670. doi:10.1681/ASN.2018030271.
   PubMed Web of Science ®Google Scholar
• Siegel CA, Melmed GY. Predicting response to anti-TNF agents for the treatment of Crohn’s disease. Therap Adv Gastroenterol. 2009;2(4):245–251. doi:10.1177/1756283X09336364.
   PubMedGoogle Scholar
• Arijs I, Li K, Toedter G, Quintens R, Van Lommel L, Van Steen K, Leemans P, De Hertogh G, Lemaire K, Ferrante M, et al. Mucosal gene signatures to predict response to infliximab in patients with ulcerative colitis. Gut. 2009;58(12):1612–1619. doi:10.1136/gut.2009.178665.
   PubMed Web of Science ®Google Scholar
• Gevers D, Kugathasan S, Denson LA, Vazquez-Baeza Y, Van Treuren W, Ren B, Schwager E, Knights D, Song SJ, Yassour M, et al. The treatment-naive microbiome in new-onset Crohn’s disease. Cell Host & Microbe. 2014;15:382–392. doi:10.1016/j.chom.2014.02.005.
   PubMed Web of Science ®Google Scholar
• Lewis JD, Chen EZ, Baldassano RN, Otley AR, Griffiths AM, Lee D, Bittinger K, Bailey A, Friedman ES, Hoffmann C, et al. Inflammation, antibiotics, and diet as environmental stressors of the gut microbiome in pediatric Crohn’s disease. Cell Host & Microbe. 2015;18:489–500. doi:10.1016/j.chom.2015.09.008.
   PubMed Web of Science ®Google Scholar
• Ungaro R, Bernstein CN, Gearry R, Hviid A, Kolho KL, Kronman MP, Shaw S, Van Kruiningen H, Colombel JF, Atreja A. Antibiotics associated with increased risk of new-onset Crohn’s disease but not ulcerative colitis: a meta-analysis. Am J Gastroenterol. 2014;109:1728–1738. doi:10.1038/ajg.2014.246.
   PubMed Web of Science ®Google Scholar
• Ihekweazu FD, Fofanova TY, Queliza K, Nagy-Szakal D, Stewart CJ, Engevik MA, Hulten KG, Tatevian N, Graham DY, Versalovic J, et al. Bacteroides ovatus ATCC 8483 monotherapy is superior to traditional fecal transplant and multi-strain bacteriotherapy in a murine colitis model. Gut Microbes. 2019;10:504–520. doi:10.1080/19490976.2018.1560753.
   PubMed Web of Science ®Google Scholar
• Shaw KA, Bertha M, Hofmekler T, Chopra P, Vatanen T, Srivatsa A, Prince J, Kumar A, Sauer C, Zwick ME, et al. Dysbiosis, inflammation, and response to treatment: a longitudinal study of pediatric subjects with newly diagnosed inflammatory bowel disease. Genome Med. 2016;8:75. doi:10.1186/s13073-016-0331-y.
   PubMed Web of Science ®Google Scholar
• Kong L, Lloyd-Price J, Vatanen T, Seksik P, Beaugerie L, Simon T, Vlamakis H, Sokol H, Xavier RJ. Linking strain engraftment in fecal microbiota transplantation with maintenance of remission in Crohn’s disease. Gastroenterology. 2020;159(6):2193–2202.e5. doi:10.1053/j.gastro.2020.08.045.
   PubMed Web of Science ®Google Scholar
• Lee JWJ, Plichta D, Hogstrom L, Borren NZ, Lau H, Gregory SM, Tan W, Khalili H, Clish C, Vlamakis H, et al. Multi-omics reveal microbial determinants impacting responses to biologic therapies in inflammatory bowel disease. Cell Host & Microbe. 2021;29(8):1294–1304.e4. doi:10.1016/j.chom.2021.06.019.
   PubMed Web of Science ®Google Scholar
• Jia W, Xie G, Jia W. Bile acid–microbiota crosstalk in gastrointestinal inflammation and carcinogenesis. Nat Rev Gastroenterol Hepatol. 2018;15(2):111–128. doi:10.1038/nrgastro.2017.119.
   PubMed Web of Science ®Google Scholar
• Duboc H, Rajca S, Rainteau D, Benarous D, Maubert MA, Quervain E, Thomas G, Barbu V, Humbert L, Despras G, et al. Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases. Gut. 2013;62:531–539. doi:10.1136/gutjnl-2012-302578.
   PubMed Web of Science ®Google Scholar
• Hua YL, Jia YQ, Zhang XS, Yuan ZW, Ji P, Hu JJ, Wei YM. Baitouweng Tang ameliorates DSS-induced ulcerative colitis through the regulation of the gut microbiota and bile acids via pathways involving FXR and TGR5. Biomed Pharmacother. 2021;137:111320. doi:10.1016/j.biopha.2021.111320.
   PubMed Web of Science ®Google Scholar
• Lajczak-McGinley NK, Porru E, Fallon CM, Smyth J, Curley C, McCarron PA, Tambuwala MM, Roda A, Keely SJ. The secondary bile acids, ursodeoxycholic acid and lithocholic acid, protect against intestinal inflammation by inhibition of epithelial apoptosis. Physiol Rep. 2020;8:e14456. doi:10.14814/phy2.14456.
   PubMed Web of Science ®Google Scholar
• Goyal N, Rana A, Bijjem KR, Kumar P. Effect of chenodeoxycholic acid and sodium hydrogen sulfide in dinitro benzene sulfonic acid (DNBS) – Induced ulcerative colitis in rats. Pharmacol Rep. 2015;67(3):616–623. doi:10.1016/j.pharep.2014.12.018.
   PubMed Web of Science ®Google Scholar
• Baars A, Oosting A, Knol J, Garssen J, van Bergenhenegouwen J. The gut microbiota as a therapeutic target in IBD and metabolic disease: a role for the bile acid receptors FXR and TGR5. Microorganisms. 2015;3:641–666. doi:10.3390/microorganisms3040641.
   PubMedGoogle Scholar
• Ke J, Li Y, Han C, He R, Lin R, Qian W, Hou X. Fucose ameliorate intestinal inflammation through modulating the crosstalk between bile acids and gut microbiota in a chronic colitis murine model. Inflamm Bowel Dis. 2020;26:863–873. doi:10.1093/ibd/izaa007.
   PubMed Web of Science ®Google Scholar
• Sinha SR, Haileselassie Y, Nguyen LP, Tropini C, Wang M, Becker LS, Sim D, Jarr K, Spear ET, Singh G, et al. Dysbiosis-induced secondary bile acid deficiency promotes intestinal inflammation. Cell Host & Microbe. 2020;27(4):659–670.e5. doi:10.1016/j.chom.2020.01.021.
   PubMed Web of Science ®Google Scholar
• Carino A, Biagioli M, Marchiano S, Fiorucci C, Bordoni M, Roselli R, Di Giorgio C, Baldoni M, Ricci P, Monti MC, et al. Opposite effects of the FXR agonist obeticholic acid on Mafg and Nrf2 mediate the development of acute liver injury in rodent models of cholestasis. Biochim Biophys Acta Mol Cell Biol Lipids. 2020;1865(9):158733. doi:10.1016/j.bbalip.2020.158733.
   PubMed Web of Science ®Google Scholar
• Fiorucci S, Distrutti E. The pharmacology of bile acids and their receptors. Handb Exp Pharmacol. 2019;256:3–18. doi:10.1007/164_2019_238.
   PubMedGoogle Scholar
• Alemi F, Poole DP, Chiu J, Schoonjans K, Cattaruzza F, Grider JR, Bunnett NW, Corvera CU. The receptor TGR5 mediates the prokinetic actions of intestinal bile acids and is required for normal defecation in mice. Gastroenterology. 2013;144:145–154. doi:10.1053/j.gastro.2012.09.055.
   PubMed Web of Science ®Google Scholar
• Ward JBJ, Lajczak NK, Kelly OB, O’Dwyer AM, Giddam AK, Ni Gabhann J, Franco P, Tambuwala MM, Jefferies CA, Keely S, et al. Ursodeoxycholic acid and lithocholic acid exert anti-inflammatory actions in the colon. Am J Physiol Gastrointest Liver Physiol. 2017;312:G550–G558. doi:10.1152/ajpgi.00256.2016.
   PubMed Web of Science ®Google Scholar
• Ajouz H, Mukherji D, Shamseddine A. Secondary bile acids: an underrecognized cause of colon cancer. World J Surg Oncol. 2014;12:164. doi:10.1186/1477-7819-12-164.
   PubMed Web of Science ®Google Scholar
• Payne CM, Bernstein C, Dvorak K, Bernstein H. Hydrophobic bile acids, genomic instability, Darwinian selection, and colon carcinogenesis. Clin Exp Gastroenterol. 2008;1:19–47. doi:10.2147/ceg.s4343.
   PubMedGoogle Scholar