Role of intestinal microbiota in the formation of non-alcoholic fatty liver disease
- Authors: Akhmedov VA1, Gaus OV1
-
Affiliations:
- Omsk State Medical University of the Ministry of Health of the Russian Federation
- Issue: Vol 91, No 2 (2019)
- Pages: 143-148
- Section: Editorial
- URL: https://journals.rcsi.science/0040-3660/article/view/32973
- DOI: https://doi.org/10.26442/00403660.2019.02.000051
- ID: 32973
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Abstract
The article provides an overview of modern views on the role of intestinal microbiota in the formation of non-alcoholic fatty liver disease. The general questions of the pathogenesis of the syndrome of excessive bacterial growth in the intestine, the participation of opportunistic microflora, the deficit of representatives of normal microflora, changes in the species composition of bile acids in the pathogenesis of nonalcoholic fatty liver disease are considered.
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##article.viewOnOriginalSite##About the authors
V A Akhmedov
Omsk State Medical University of the Ministry of Health of the Russian Federation
Email: v_akhmedov@mail.ru
д.м.н., проф., зав. каф. медицинской реабилитации дополнительного профессионального образования Omsk, Russia
O V Gaus
Omsk State Medical University of the Ministry of Health of the Russian Federationк.м.н, ассистент каф. факультетской терапии, профессиональных болезней Omsk, Russia
References
- Bellentani S. The epidemiology of non - alcoholic fatty liver disease. Liver Int. 2017;37(Suppl. 1):81-4. doi: 10.1111/liv.13299
- Bellentani S, Scaglioni F, Marino M, Bedogni G. Epidemiology of non - alcoholic fatty liver disease. Dig Dis. 2010;28(1):155-61. doi: 10.1159/000282080
- Zak-Golab A, Olszanecka-Glinianowicz M, Kocelak P, Chudek J. The role of gut microbiota in the pathogenesis of obesity. Post Hig Med Dosw Postepy Hig Med Dosw (Online). 2014;68:84-90. doi: 10.5604/17322693.1086419
- Balmer M.L, Slack E, de Gottardi A, Lawson M.A, Hapfelmeier S, Miele L, Grieco A, van Vlierberghe H, Fahrner R, Patuto N, Bernsmeier C, Ronchi F, Wyss M, Stroka D, Dickgreber N, Heim M.H, Mc Coy K.D, Macpherson A.J. The liver may act as a firewall mediating mutualism between the host and its gut commensal microbiota. Sci Transl Med. 2014;6(237):237-66. doi: 10.1126/scitranslmed.3008618
- Luther J, Garber J.J, Khalili H, Dave M, Bale S.S, Jindal R, Motola D.L, Luther S, Bohr S, Jeoung S.W, Deshpande V, Singh G, Turner J.R, Yarmush M.L, Chung R.T, Patel S. Hepatic Injury in Nonalcoholic Steatohepatitis Contributes to Altered Intestinal Permeability. Cell Mol Gastroenterol Hepatol. 2015;1(2):222-32. doi: 10.1016/ j.jcmgh.2015.01.001
- Miele L, Valenza V, La Torre G, Montalto M, Cammarota G, Ricci R, Mascianà R, Forgione A, Gabrieli M.L, Perotti G, Vecchio F.M, Rapaccini G, Gasbarrini G, Day C.P, Grieco A. Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. Hepatology. 2009;49(6):1877-87. doi: 10.1002/hep.22848
- Wong V.W, Wong G.L, Chan H.Y, Yeung D.K, Chan R.S, Chim A.M, Chan C.K, Tse Y.K, Woo J, Chu W.C, Chan H.L. Bacterial endotoxin and non - alcoholic fatty liver disease in the general population: a prospective cohort study. Aliment Pharmacol Ther. 2015;42(6):731-40. doi: 10.1111/apt.13327
- Boursier J, Mueller O, Barret M, Machado M, Fizanne L, Araujo-Perez F, Guy C.D, Seed P.C, Rawls J.F, David L.A, Hunault G, Oberti F, Calès P, Diehl A.M. The severity of nonalcoholic fatty liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota. Hepatology. 2016;63(3):764-75. doi: 10.1002/hep.28356
- Bäckhed F, Ding H, Wang T, Hooper L.V, Koh G.Y, Nagy A, Semenkovich C.F, Gordon J.I. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A. 2004;101(44):15718-23. doi: 10.1073/pnas.0407076101
- Bäckhed F, Manchester J.K, Semenkovich C.F, Gordon J.I. Mechanisms underlying the resistance to diet - induced obesity in germ - free mice. Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):979-84. doi: 10.1073/pnas.0605374104
- Jiang C, Xie C, Li F, Zhang L, Nichols R.G, Krausz K.W, Cai J, Qi Y, Fang Z.Z, Takahashi S, Tanaka N, Desai D, Amin S.G, Albert I, Patterson A.D, Gonzalez F.J. Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease. J Clin Invest. 2015;125(1):386-402. doi: 10.1172/JCI76738
- Sayin S.I, Wahlström A, Felin J, Jäntti S, Marschall H.U, Bamberg K, Angelin B, Hyötyläinen T, Orešič M, Bäckhed F. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro - beta - muricholic acid, a naturally occurring FXR antagonist. Cell Metab. 2013;17(2):225-35. doi: 10.1016/j.cmet.2013.01.003
- Kersten S, Mandard S, Tan N.S, Escher P, Metzger D, Chambon P, Gonzalez F.J, Desvergne B, Wahli W. Characterization of the fasting - induced adipose factor FIAF, a novel peroxisome proliferator - activated receptor target gene. J Biol Chem. 2000;275(37):28488-93. doi: 10.1074/jbc.M004029200
- Romano K.A, Vivas E.I, Amador-Noguez D, Rey F.E. Intestinal microbiota composition modulates choline bioavailability from diet and accumulationof the proatherogenic metabolite trimethylamine-N-oxide. MBio. 2015;6(2):e02481. doi: 10.1128/mBio.02481-14
- Dumas M.E, Barton R.H, Toye A, Cloarec O, Blancher C, Rothwell A, Fearnside J, Tatoud R, Blanc V, Lindon J.C, Mitchell S.C, Holmes E, Mc Carthy M.I, Scott J, Gauguier D, Nicholson J.K. Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin - resistant mice. Proc Natl Acad Sci U S A. 2006;103(33):12511-6. doi: 10.1073/pnas.0601056103
- Bennett B.J, de Aguiar Vallim T.Q, Wang Z, Shih D.M, Meng Y, Gregory J, Allayee H, Lee R, Graham M, Crooke R, Edwards P.A, Hazen S.L, Lusis A.J. Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex geneticand dietary regulation. Cell Metab. 2013 Jan 8;17(1):49-60. doi: 10.1016/j.cmet.2012.12.011
- Koeth R.A, Wang Z, Levison B.S, Buffa J.A, Org E, Sheehy B.T, Britt E.B, Fu X, Wu Y, Li L, Smith J.D, Di-Donato J.A, Chen J, Li H, Wu G.D, Lewis J.D, Warrier M, Brown J.M, Krauss R.M, Tang W.H, Bushman F.D, Lusis A.J, Hazen S.L. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013;19(5):576-85. doi: 10.1038/nm.3145
- Chen Y.M, Liu Y, Zhou R.F, Chen X.L, Wang C, Tan X.Y, Wang L.J, Zheng R.D, Zhang H.W, Ling W.H, Zhu H.L. Associations of gut - flora - dependent metabolite trimethylamine-N-oxide, betaine and choline with non - alcoholic fatty liver disease in adults. Sci Rep. 2016;6:19076. doi: 10.1038/srep19076
- Tang W.H, Hazen S.L. Microbiome, trimethylamine N-oxide, and cardiometabolic disease. Transl Res. 2017;179:108-15. doi: 10.1016/ j.trsl.2016.07.007
- Takaki A, Kawai D, Yamamoto K. Multiple hits, including oxidative stress, as pathogenesis and treatment target in non - alcoholic steatohepatitis (NASH). Int J Mol Sci. 2013;14(10):20704-28. doi: 10.3390/ijms141020704
- Valentini M, Piermattei A, Di Sante G, Migliara G, Delogu G, Ria F. Immunomodulation by gut microbiota: role of Toll - like receptor expressed by T cells. J Immunol Res. 2014;2014:586939. doi: 10.1155/2014/586939
- Kim J.J, Sears D.D. TLR4 and Insulin Resistance. Gastroenterol Res Pract. 2010;2010:212563. doi: 10.1155/2010/212563
- Neal M.D, Leaphart C, Levy R, Prince J, Billiar T.R, Watkins S, Li J, Cetin S, Ford H, Schreiber A, Hackam D.J. Enterocyte TLR4 mediates phagocytosis and translocation of bacteria across the intestinalbarrier. J Immunol. 2006;176(5):3070-9.
- Wang Y, Ghoshal S, Ward M, de Villiers W, Woodward J, Eckhardt E. Chylomicrons promote intestinal absorption and systemic dissemination of dietary antigen(ovalbumin) in mice. PLoS One. 2009;4(12):e8442. doi: 10.1371/journal.pone.0008442
- Brun P, Castagliuolo I, Di Leo V, Buda A, Pinzani M, Palù G, Martines D. Increased intestinal permeability in obese mice: new evidence in the pathogenesis of nonalcoholic steatohepatitis. Am J Physiol Gastrointest Liver Physiol. 2007;292(2):G518-525.
- Beutler B, Hoebe K, Du X, Ulevitch R.J. How we detect microbes and respond to them: the Toll - like receptors and their transducers. J Leukoc Biol. 2003;74(4):479-85. doi: 10.1189/jlb.0203082
- Ruiz A.G, Casafont F, Crespo J, Cayón A, Mayorga M, Estebanez A, Fernadez-Escalante J.C, Pons-Romero F. Lipopolysaccharide - binding protein plasma levels and liver TNF-alpha gene expression in obesepatients: evidence for the potential role of endotoxin in the pathogenesis of non - alcoholicsteatohepatitis. Obes Surg. 2007;17(10):1374-80. doi: 10.1007/s11695-007-9243-7
- Brun P, Castagliuolo I, Pinzani M, Palù G, Martines D. Exposure to bacterial cell wall products triggers an inflammatory phenotype in hepatic stellatecells. Am J Physiol Gastrointest Liver Physiol. 2005;289(3):G571-8. doi: 10.1152/ajpgi.00537.2004
- Paik Y.H, Schwabe R.F, Bataller R, Russo M.P, Jobin C, Brenner D.A. Toll - like receptor mediates inflammatory signaling by bacterial lipopolysaccharide in human hepatic stellate cells. Hepatology. 2003;37(5):1043-55. doi: 10.1053/jhep.2003.50182
- Arroyo-Espliguero R, Avanzas P, Jeffery S, Kaski J.C. CD14 and toll - like receptor 4: a link between infection and acute coronary events? Heart. 2004;90(9):983-8. doi: 10.1136/hrt.2002.001297
- Curtiss L.K, Tobias P.S. Emerging role of Toll - like receptors in atherosclerosis. J Lipid Res. 2009;50 Suppl:340-5. doi: 10.1194/jlr.R800056-JLR200
- Purohit V, Bode J.C, Bode C, Brenner D.A, Choudhry M.A, Hamilton F, Kang Y.J, Keshavarzian A, Rao R, Sartor R.B, Swanson C, Turner J.R. Alcohol, intestinal bacterial growth, intestinal permeability to endotoxin, and medical consequences: summary of a symposium. Alcohol. 2008;42(5):349-61. doi: 10.1016/j.alcohol.2008.03.131
- Setshedi M, Wands J.R, Monte S.M. Acetaldehyde adducts in alcoholic liver disease. Oxid Med Cell Longev. 2010;3(3):178-85. doi: 10.4161/oxim.3.3.12288
- Su G.L. Lipopolysaccharides in liver injury: molecular mechanisms of Kupffer cell activation. Am J Physiol Gastrointest Liver Physiol. 2002;283(2):G256-265. doi: 10.1152/ajpgi.00550.2001
- Gustot T, Lemmers A, Moreno C, Nagy N, Quertinmont E, Nicaise C, Franchimont D, Louis H, Devière J, Le Moine O. Differential liver sensitization to Toll - like receptor pathways in mice with alcoholic fatty liver. Hepatology. 2006;43(5):989-1000. doi: 10.1002/hep.21138
- Nassir F, Ibdah J.A. Role of mitochondria in nonalcoholic fatty liver disease. Int J Mol Sci. 2014;15(5):8713-42. doi: 10.3390/ijms15058713
- Fritz R, Bol J, Hebling U, Angermüller S, Völkl A, Fahimi H.D, Mueller S. Compartment - dependent management of H(2)O(2) by peroxisomes. Free Radic Biol Med. 2007;42(7):1119-29. doi: 10.1016/j.freeradbiomed.2007.01.014
- Rolo A.P, Teodoro J.S, Palmeira C.M. Role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis. Free Radic Biol Med. 2012;52(1):59-69. doi: 10.1016/j.freeradbiomed.2011.10.003
- Mardinoglu A, Shoaie S, Bergentall M, Ghaffari P, Zhang C, Larsson E, Bäckhed F, Nielsen J. The gut microbiota modulates host amino acid and glutathione metabolism in mice. Mol Syst Biol. 2015;11(10):834. doi: 10.15252/msb.20156487
- Morgan B, Ezeriņa D, Amoako T.N, Riemer J, Seedorf M, Dick T.P. Multiple glutathione disulfide removal pathways mediate cytosolic redox homeostasis. Nat Chem Biol. 2013;9(2):119-25. doi: 10.1038/nchembio.1142
- Davila A.M, Blachier F, Gotteland M, Andriamihaja M, Benetti P.H, Sanz Y, Tomé D. Intestinal luminal nitrogen metabolism: role of the gut microbiota and consequences for the host. Pharmacol Res. 2013;68(1):95-107. doi: 10.1016/j.phrs.2012.11.005
- Brunt E.M, Kleiner D.E, Wilson L.A, Belt P, Neuschwander-Tetri BA; NASH Clinical Research Network (CRN). Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD: distinct clinicopathologic meanings. Hepatology. 2011;53(3):810-20. doi: 10.1002/hep.24127
- Malaguarnera M, Vacante M, Antic T, Giordano M, Chisari G, Acquaviva R, Mastrojeni S, Malaguarnera G, Mistretta A, Li Volti G, Galvano F. Bifidobacterium longum with fructo - oligosaccharides in patients with non alcoholic steatohepatitis. Dig Dis Sci. 2012;57(2):545-53. doi: 10.1007/s10620-011-1887-4
- Ren T, Huang C, Cheng M. Dietary blueberry and bifidobacteria attenuate nonalcoholic fatty liver disease in rats by affecting SIRT1-mediated signaling pathway. Oxid Med Cell Longev. 2014;2014:469059. doi: 10.1155/2014/469059
- Nobili V, Putignani L, Mosca A, Chierico F.D, Vernocchi P, Alisi A, Stronati L, Cucchiara S, Toscano M, Drago L. Bifidobacteria and lactobacilli in the gut microbiome of children with non - alcoholic fatty liverdisease: which strains act as health players? Arch Med Sci. 2018;14(1):81-7. doi: 10.5114/aoms.2016.62150
- Sohn W, Jun D.W, Lee K.N, Lee H.L, Lee O.Y, Choi H.S, Yoon B.C. Lactobacillus paracasei Induces M2-Dominant Kupffer Cell Polarization in a Mouse Model of Nonalcoholic Steatohepatitis. Dig Dis Sci. 2015;60(11):3340-50. doi: 10.1007/s10620-015-3770-1
- Wang B, Jiang X, Cao M, Ge J, Bao Q, Tang L, Chen Y, Li L. Altered Fecal Microbiota Correlates with Liver Biochemistry in Nonobese Patients with Non - alcoholic Fatty Liver Disease. Sci Rep. 2016;6:32002. doi: 10.1038/srep32002
- Raman M, Ahmed I, Gillevet P.M, Probert C.S, Ratcliffe N.M, Smith S, Greenwood R, Sikaroodi M, Lam V, Crotty P, Bailey J, Myers R.P, Rioux K.P. Fecal microbiome and volatile organic compound metabolome in obese humans with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2013;11(7):868-75. doi: 10.1016/j.cgh.2013.02.015
- Del Chierico F, Nobili V, Vernocchi P, Russo A, Stefanis C, Gnani D, Furlanello C, Zandonà A, Paci P, Capuani G, Dallapiccola B, Miccheli A, Alisi A, Putignani L. Gut microbiota profiling of pediatric nonalcoholic fatty liver disease and obese patients unveiledby an integrated meta - omics - based approach. Hepatology. 2017;65(2):451-64. doi: 10.1002/hep.28572
- Ohland C.L, Macnaughton W.K. Probiotic bacteria and intestinal epithelial barrier function. Am J Physiol Gastrointest Liver Physiol. 2010;298(6):807-19. doi: 10.1152/ajpgi.00243.2009
- Schwiertz A, Taras D, Schäfer K, Beijer S, Bos N.A, Donus C, Hardt P.D. Microbiota and SCFA in lean and overweight healthy subjects. Obesity (Silver Spring). 2010;18(1):190-5. doi: 10.1038/oby.2009.167
- Elshaghabee F.M, Bockelmann W, Meske D, de Vrese M, Walte H.G, Schrezenmeir J, Heller K.J. Ethanol Production by Selected Intestinal Microorganisms and Lactic Acid Bacteria Growing under Different Nutritional Conditions. Front Microbiol. 2016;7:47. doi: 10.3389/fmicb.2016.00047
- Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J, de Roos P, Liu H, Cross J.R, Pfeffer K, Coffer P.J, Rudensky A.Y. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature. 2013;504(7480):451-5. doi: 10.1038/nature12726
- Li J, Sung C.Y, Lee N, Ni Y, Pihlajamäki J, Panagiotou G, El-Nezami H. Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice. Proc Natl Acad Sci U S A. 2016;113(9):1306-15. doi: 10.1073/pnas.1518189113
- Shin N.R, Lee J.C, Lee H.Y, Kim M.S, Whon T.W, Lee M.S, Bae J.W. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet - induced obese mice. Gut. 2014;63(5):727-35. doi: 10.1136/gutjnl-2012-303839
- Everard A, Belzer C, Geurts L, Ouwerkerk J.P, Druart C, Bindels L.B, Guiot Y, Derrien M, Muccioli G.G, Delzenne N.M, de Vos W.M, Cani P.D. Cross - talk between Akkermansia muciniphila and intestinal epithelium controls diet - induced obesity. Proc Natl Acad Sci U S A. 2013;110(22):9066-71. doi: 10.1073/pnas.1219451110
- Bach Knudsen K.E. Microbial degradation of whole - grain complex carbohydrates and impact on short - chain fatty acids and health. Adv Nutr. 2015;6(2):206-13. doi: 10.3945/an.114.007450
- Den Besten G, van Eunen K, Groen A.K, Venema K, Reijngoud D.J, Bakker B.M. The role of short - chain fatty acids in the interplay between diet, gut microbiota, and host energymetabolism. J Lipid Res. 2013;54(9):2325-40. doi: 10.1194/jlr.R036012
- Turnbaugh P.J, Ley R.E, Mahowald M.A, Magrini V, Mardis E.R, Gordon J.I. An obesity - associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444(7122):1027-31. doi: 10.1038/nature05414
- Kimura I, Ozawa K, Inoue D, Imamura T, Kimura K, Maeda T, Terasawa K, Kashihara D, Hirano K, Tani T, Takahashi T, Miyauchi S, Shioi G, Inoue H, Tsujimoto G. The gut microbiota suppresses insulin - mediated fat accumulation via the short - chain fatty acidreceptor GPR43. Nat Commun. 2013;4:1829. doi: 10.1038/ncomms2852
- Maslowski K.M, Vieira A.T, Ng A, Kranich J, Sierro F, Yu D, Schilter H.C, Rolph M.S, Mackay F, Artis D, Xavier R.J, Teixeira M.M, Mackay C.R. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature. 2009;461(7268):1282-6. doi: 10.1038/nature08530
- Claus S.P, Tsang T.M, Wang Y, Cloarec O, Skordi E, Martin F.P, Rezzi S, Ross A, Kochhar S, Holmes E, Nicholson J.K. Systemic multicompartmental effects of the gut microbiome on mouse metabolic phenotypes. Mol Syst Biol. 2008;4:219. doi: 10.1038/msb.2008.56
- Yuan L, Bambha K. Bile acid receptors and nonalcoholic fatty liver disease. World J Hepatol. 2015;7(28):2811-8. doi: 10.4254/wjh.v7.i28.2811
- Ridaura V.K, Faith J.J, Rey F.E, Cheng J, Duncan A.E, Kau A.L, Griffin N.W, Lombard V, Henrissat B, Bain J.R, Muehlbauer M.J, Ilkayeva O, Semenkovich C.F, Funai K, Hayashi D.K, Lyle B.J, Martini M.C, Ursell L.K, Clemente J.C, van Treuren W, Walters W.A, Knight R, Newgard C.B, Heath A.C, Gordon J.I. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science. 2013;341(6150):1241214. doi: 10.1126/science.1241214
- Huang W, Ma K, Zhang J, Qatanani M, Cuvillier J, Liu J, Dong B, Huang X, Moore D.D. Nuclear receptor - dependent bile acid signaling is required for normal liver regeneration. Science. 2006;312(5771):233-6. doi: 10.1126/science.1121435
- De Aguiar Vallim T.Q, Tarling E.J, Edwards P.A. Pleiotropic roles of bile acids in metabolism. Cell Metab. 2013;17(5):657-69. doi: 10.1016/j.cmet.2013.03.013
- Neuschwander-Tetri B.A, Loomba R, Sanyal A.J, Lavine J.E, van Natta M.L, Abdelmalek M.F, Chalasani N, Dasarathy S, Diehl A.M, Hameed B, Kowdley K.V, Mc Cullough A, Terrault N, Clark J.M, Tonascia J, Brunt E.M, Kleiner D.E, Doo E; NASH Clinical Research Network. Farnesoid X nuclear receptor ligand obetic holic acid for non - cirrhotic, non - alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo - controlled trial. Lancet. 2015;385(9972):956-65. doi: 10.1016/S0140-6736(14)61933-4
- Cariou B. The farnesoid X receptor (FXR) as a new target in non - alcoholic steatohepatitis. Diabetes Metab. 2008;34(6 Pt 2):685-91. doi: 10.1016/S1262-3636(08)74605-6
- Watanabe M, Horai Y, Houten S.M, Morimoto K, Sugizaki T, Arita E, Mataki C, Sato H, Tanigawara Y, Schoonjans K, Itoh H, Auwerx J. Lowering bile acid pool size with a synthetic farnesoid X receptor (FXR) agonist induces obesityand diabetes through reduced energy expenditure. J Biol Chem. 2011;286(30):26913-20. doi: 10.1074/jbc.M111.248203
- Houten S.M, Volle D.H, Cummins C.L, Mangelsdorf D.J, Auwerx J. In vivo imaging of farnesoid X receptor activity reveals the ileum as the primary bile acidsignaling tissue. Mol Endocrinol. 2007;21(6):1312-23. doi: 10.1210/me.2007-0113
- Jiang C, Xie C, Lv Y, Li J, Krausz K.W, Shi J, Brocker C.N, Desai D, Amin S.G, Bisson W.H, Liu Y, Gavrilova O, Patterson A.D, Gonzalez F.J. Intestine - selective farnesoid X receptor inhibition improves obesity - related metabolic dysfunction. Nat Commun. 2015 Dec 15;6:10166. doi: 10.1038/ncomms10166
- Fang S, Suh J.M, Reilly S.M, Yu E, Osborn O, Lackey D, Yoshihara E, Perino A, Jacinto S, Lukasheva Y, Atkins A.R, Khvat A, Schnabl B, Yu R.T, Brenner D.A, Coulter S, Liddle C, Schoonjans K, Olefsky J.M, Saltiel A.R, Downes M, Evans R.M. Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulinresistance. Nat Med. 2015;21(2):159-65. doi: 10.1038/nm.3760
- Mouzaki M, Wang A.Y, Bandsma R, Comelli E.M, Arendt B.M, Zhang L, Fung S, Fischer S.E, Mc Gilvray I.G, Allard J.P. Bile Acids and Dysbiosis in Non-Alcoholic Fatty Liver Disease. PLoS One. 2016;11(5):e0151829. doi: 10.1371/journal.pone.0151829