Gut microbiota as a therapeutic target for metabolic disorders

Current Medicinal Chemistry

Volumn 25, Issue 9, 2018, Pages 984-1001

  Okubo, Hirofumi ^a   Nakatsu, Yusuke ^a   Kushiyama, Akifumi ^b   Yamamotoya, Takeshi ^a   Matsunaga, Yasuka ^a   Inoue, Masa Ki ^a   Fujishiro, Midori ^c   Sakoda, Hideaki ^d   Ohno, Haruya ^a   Yoneda, Masayasu ^a   Ono, Hiraku ^e   Asano, Tomoichiro ^a  

^a HIROSHIMA UNIVERSITY   (Japan)

^b INSTITUTE FOR ADULT DISEASES   (Japan)

^c NIHON UNIVERSITY SCHOOL OF MEDICINE   (Japan)

^d UNIVERSITY OF MIYAZAKI   (Japan)

^e CHIBA UNIVERSITY   (Japan)

Author keywords

Fecal microbiota transplantation; Gut microbiota; Non alcoholic fatty liver disease; Obesity; Prebiotics; Probiotics; Type 2 diabetes mellitus

Indexed keywords

DEFENSE MECHANISM; ENERGY EXPENDITURE; ENERGY METABOLISM; FECAL MICROBIOTA TRANSPLANTATION; FOOD INTAKE; GLUCONEOGENESIS; HUMAN; INSULIN RESISTANCE; INTESTINE FLORA; METABOLIC DISORDER; NON INSULIN DEPENDENT DIABETES MELLITUS; NONALCOHOLIC FATTY LIVER; NONHUMAN; OBESITY; REVIEW; ANIMAL; MICROBIOLOGY; MOLECULARLY TARGETED THERAPY;

PREBIOTIC AGENT; PROBIOTIC AGENT;

ANIMALS; DIABETES MELLITUS, TYPE 2; FECAL MICROBIOTA TRANSPLANTATION; GASTROINTESTINAL MICROBIOME; HUMANS; MOLECULAR TARGETED THERAPY; NON-ALCOHOLIC FATTY LIVER DISEASE; OBESITY; PREBIOTICS; PROBIOTICS;

EID: 85048465721     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/0929867324666171009121702     Document Type: Review

References (132)

1. Tilg, H.; Kaser, A. Gut microbiome, obesity, and metabolic dysfunction. J. Clin. Invest., 2011, 121(6), 2126-2132.
2. Bouter, K.E.; van Raalte, D.H.; Groen, A.K.; Nieuwdorp, M. Role of the gut microbiome in the pathogenesis of obesity and obesity-related metabolic dysfunction. Gastroenterology, 2017, 152(7), 1671-1678.
3. Xu, J.; Gordon, J.I. Honor thy symbionts. Proc. Natl. Acad. Sci. USA, 2003, 100(18), 10452-10459.
4. Sommer, F.; Bäckhed, F. The gut microbiota--masters of host development and physiology. Nat. Rev. Microbiol., 2013, 11(4), 227-238.
5. Eckburg, P.B.; Bik, E.M.; Bernstein, C.N.; Purdom, E.; Dethlefsen, L.; Sargent, M.; Gill, S.R.; Nelson, K.E.; Relman, D.A. Diversity of the human intestinal microbial flora. Science, 2005, 308(5728), 1635-1638.
6. Gill, S.R.; Pop, M.; Deboy, R.T.; Eckburg, P.B.; Turnbaugh, P.J.; Samuel, B.S.; Gordon, J.I.; Relman, D.A.; Fraser-Liggett, C.M.; Nelson, K.E. Metagenomic analysis of the human distal gut microbiome. Science, 2006, 312(5778), 1355-1359.
7. Noverr, M.C.; Huffnagle, G.B. Does the microbiota regulate immune responses outside the gut? Trends Microbiol., 2004, 12(12), 562-568.
8. Vrieze, A.; Holleman, F.; Zoetendal, E.G.; de Vos, W.M.; Hoekstra, J.B.; Nieuwdorp, M. The environment within: how gut microbiota may influence metabolism and body composition. Diabetologia, 2010, 53(4), 606-613.
9. Viggiano, D.; Ianiro, G.; Vanella, G.; Bibbò, S.; Bruno, G.; Simeone, G.; Mele, G. Gut barrier in health and disease: Focus on childhood. Eur. Rev. Med. Pharmacol. Sci., 2015, 19(6), 1077-1085.
10. 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. USA, 2004, 101(44), 15718-15723.
11. Ley, R.E.; Bäckhed, F.; Turnbaugh, P.; Lozupone, C.A.; Knight, R.D.; Gordon, J.I. Obesity alters gut microbial ecology. Proc. Natl. Acad. Sci. USA, 2005, 102(31), 11070-11075.
12. 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), 1027-1031.
13. Turnbaugh, P.J.; Bäckhed, F.; Fulton, L.; Gordon, J.I. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe, 2008, 3(4), 213-223.
14. Ley, R.E.; Turnbaugh, P.J.; Klein, S.; Gordon, J.I. Microbial ecology: human gut microbes associated with obesity. Nature, 2006, 444(7122), 1022-1023.
15. Duncan, S.H.; Lobley, G.E.; Holtrop, G.; Ince, J.; Johnstone, A.M.; Louis, P.; Flint, H.J. Human colonic microbiota associated with diet, obesity and weight loss. Int. J. Obes., 2008, 32(11), 1720-1724.
16. 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), 201018(1), 190-195.
17. Turnbaugh, P.J.; Hamady, M.; Yatsunenko, T.; CantarelB.L.; Duncan, A.; Ley, R.E.; Sogin, M.L.; Jones, W.J.; RoeB.A.; Affourtit, J.P.; Egholm, M.; Henrissat, B.; HeathA.C.; Knight, R.; Gordon, J.I. A core gut microbiome in obese and lean twins. Nature, 2009, 457(7228), 480-484.
18. Gong, D.; Gong, X.; Wang, L.; Yu, X.; Dong, Q. Involvement of reduced microbial diversity in inflammatory bowedisease. Gastroenterol. Res. Pract., 2009, 2016(2016)6951091.
19. Brahe, L.K.; Astrup, A.; Larsen, L.H. Is butyrate the link between diet, intestinal microbiota and obesity-related metabolic diseases? Obes. Rev., 2013, 14(12), 950-959.
20. Fernandes, J.; Su, W.; Rahat-Rozenbloom, S.; WoleverT.M.; Comelli, E.M. Adiposity, gut microbiota and faecashort chain fatty acids are linked in adult humans. NutrDiabetes, 2014, 4, e121.
21. Goffredo, M.; Mass, K.; Parks, E.J.; Wagner, D.A., McClure, E.A.; Graf, J.; Savoye, M.; Pierpont, B.; Cline G.; Santoro, N. Role of Gut Microbiota and Short Chain Fatty Acids in Modulating Energy Harvest and Fat Partitioning in Youth. J. Clin. Endocrinol. Metab., 2016, 101(11), 4367-4376.
22. Hamer, H.M.; Jonkers, D.; Venema, K.; Vanhoutvin, S.Troost, F.J.; Brummer, R.J. Review article: the role of butyrate on colonic function. Aliment. Pharmacol. Ther.2008, 27(2), 104-119.
23. Cummings, J.H.; Pomare, E.W.; Branch, W.J.; NaylorC.P.; Macfarlane, G.T. Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut, 198728(10), 1221-1227.
24. 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 hosenergy metabolism. J. Lipid Res., 2013, 54(9), 2325-2340.
25. Topping, D.L.; Clifton, P.M. Short-chain fatty acids and human colonic function: roles of resistant starch and non-starch polysaccharides. Physiol. Rev., 2001, 81(3), 1031-1064.
26. Brown, A.J.; Goldsworthy, S.M.; Barnes, A.A.; EilertM.M.; Tcheang, L.; Daniels, D.; Muir, A.I.; WigglesworthM.J.; Kinghorn, I.; Fraser, N.J.; Pike, N.B.; Strum, J.C.Steplewski, K.M.; Murdock, P.R.; Holder, J.C.; MarshallF.H.; Szekeres, P.G.; Wilson, S.; Ignar, D.M.; Foord, S.M.Wise, A.; Dowell, S.J. The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J. Biol. Chem., 2003278(13), 11312-11319.
27. Le Poul, E.; Loison, C.; Struyf, S.; Springael, J.Y.; LannoyV.; Decobecq, M.E.; Brezillon, S.; Dupriez, V.; Vassart, G.Van Damme, J.; Parmentier, M.; Detheux, M. Functionacharacterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. JBiol. Chem., 2003, 278(28), 25481-25489.
28. Karaki, S.; Tazoe, H.; Hayashi, H.; Kashiwabara, H.Tooyama, K.; Suzuki, Y.; Kuwahara, A. Expression of the short-chain fatty acid receptor, GPR43, in the human colonJ. Mol. Histol., 2008, 39(2), 135-142.
29. Tazoe, H.; Otomo, Y.; Karaki, S.; Kato, I.; Fukami, Y.Terasaki, M.; Kuwahara, A. Expression of short-chain fatty acid receptor GPR41 in the human colon. Biomed. Res.2009, 30(3), 149-156.
30. Theodorakis, M.J.; Carlson, O.; Michopoulos, S.; DoyleM.E.; Juhaszova, M.; Petraki, K.; Egan, J.M. Human duodenal enteroendocrine cells: source of both incretin peptides, GLP-1 and GIP. Am. J. Physiol. Endocrinol. Metab.2006, 290(3), E550-E559.
31. Habib, A.M.; Richards, P.; Rogers, G.J.; Reimann, F.Gribble, F.M. Co-localisation and secretion of glucagon-like peptide 1 and peptide YY from primary cultured human L cells. Diabetologia, 2013, 56(6), 1413-1416.
32. Samuel, B.S.; Shaito, A.; Motoike, T.; Rey, F.E.; BackhedF.; Manchester, J.K.; Hammer, R.E.; Williams, S.C.; Crowley, J.; Yanagisawa, M.; Gordon, J.I. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. ProcNatl. Acad. Sci. USA, 2008, 105(43), 16767-16772.
33. Frost, G.; Sleeth, M.L.; Sahuri-Arisoylu, M.; Lizarbe, B.Cerdan, S.; Brody, L.; Anastasovska, J.; Ghourab, S.Hankir, M.; Zhang, S.; Carling, D.; Swann, J.R.; GibsonG.; Viardot, A.; Morrison, D.; Louise Thomas, E.; Bell, J.DThe short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nat. Commun., 2014, 53611.
34. De Vadder, F.; Kovatcheva-Datchary, P.; Goncalves, D.Vinera, J.; Zitoun, C.; Duchampt, A.; Bäckhed, F.Mithieux, G. Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell, 2014156(1-2), 84-96.
35. Kimura, I.; Ozawa, K.; Inoue, D.; Imamura, T.; Kimura, K.Maeda, T.; Terasawa, K.; Kashihara, D.; Hirano, K.; TaniT.; Takahashi, T.; Miyauchi, S.; Shioi, G.; Inoue, H.; Tsujimoto, G. The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptoGPR43. Nat. Commun., 2013, 4, 1829.
36. Ridaura, V.K.; Faith, J.J.; Rey, F.E.; Cheng, J.; DuncanA.E.; Kau, A.L.; Griffin, N.W.; Lombard, V.; Henrissat, B.Bain, J.R.; Muehlbauer, M.J.; Ilkayeva, O.; SemenkovichC.F.; Funai, K.; Hayashi, D.K.; Lyle, B.J.; Martini, M.C.Ursell, L.K.; Clemente, J.C.; Van Treuren, W.; WaltersW.A.; Knight, R.; Newgard, C.B.; Heath, A.C.; Gordon, J.IGut microbiota from twins discordant for obesity modulate metabolism in mice. Science, 2013, 341(6150), 1241214.
37. Canfora, E.E.; Jocken, J.W.; Blaak, E.E. Short-chain fatty acids in control of body weight and insulin sensitivity. NatRev. Endocrinol., 2015, 11(10), 577-591.
38. Alex, S.; Lichtenstein, L.; Dijk, W.; Mensink, R.P.; TanN.S.; Kersten, S. ANGPTL4 is produced by enteroendocrine cells in the human intestinal tract. HistochemCell Biol., 2014, 141(4), 383-391.
39. Robciuc, M.R.; Naukkarinen, J.; Ortega-Alonso, A.Tyynismaa, H.; Raivio, T.; Rissanen, A.; Kaprio, J.Ehnholm, C.; Jauhiainen, M.; Pietiläinen, K.H. Serum angiopoietin-like 4 protein levels and expression in adipose tissue are inversely correlated with obesity in monozygotic twins. J. Lipid Res., 2011, 52(8), 1575-1582.
40. Delzenne, N.M.; Neyrinck, A.M.; Bäckhed, F.; Cani, P.DTargeting gut microbiota in obesity: Effects of prebiotics and probiotics. Nat. Rev. Endocrinol., 2011, 7(11), 639-646
41. Zhang, C.; Zhang, M.; Wang, S.; Han, R.; Cao, Y.; HuaW.; Mao, Y.; Zhang, X.; Pang, X.; Wei, C.; Zhao, G.; ChenY.; Zhao, L. Interactions between gut microbiota, host genetics and diet relevant to development of metabolic syndromes in mice. ISME J., 2010, 4(2), 232-241.
42. Roberfroid, M. Prebiotics: the concept revisited. J. Nutr.2007, 137(3 Suppl. 2), 830-837.
43. Upadhyaya, B.; McCormack, L.; Fardin-Kia, A.R.; Juene-mann, R.; Nichenametla, S.; Clapper, J.; Specker, B.; DeyM. Impact of dietary resistant starch type 4 on human gumicrobiota and immunometabolic functions. Sci. Rep.2016, 6, 28797.
44. Hill, C.; Guarner, F.; Reid, G.; Gibson, G.R.; MerensteinD.J.; Pot, B.; Morelli, L.; Canani, R.B.; Flint, H.J.; Salminen, S.; Calder, P.C.; Sanders, M.E. Expert consensus document. The International Scientific Association for Pro-biotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat. Rev. Gastroenterol. Hepatol., 2014, 11(8), 506-514.
45. Kadooka, Y.; Sato, M.; Imaizumi, K.; Ogawa, A.; Ikuyama, K.; Akai, Y.; Okano, M.; Kagoshima, M.; Tsuchida, T. Regulation of abdominal adiposity by probiotics (Lactoba-cillus gasseri SBT2055) in adults with obese tendencies in a randomized controlled trial. Eur. J. Clin. Nutr., 2010, 64(6), 636-643.
46. Erejuwa, O.O.; Sulaiman, S.A.; Ab Wahab, M.S. Modulation of gut microbiota in the management of metabolic disorders: the prospects and challenges. Int. J. Mol. Sci., 2014, 15(3), 4158-4188.
47. Million, M.; Angelakis, E.; Maraninchi, M.; Henry, M.; Giorgi, R.; Valero, R.; Vialettes, B.; Raoult, D. Correlation between body mass index and gut concentrations of Lactobacillus reuteri, Bifidobacterium animalis, Methanobrevi-bacter smithii and Escherichia coli. Int. J. Obes., 2013, 37(11), 1460-1466.
48. Armougom, F.; Henry, M.; Vialettes, B.; Raccah, D.; Raoult, D. Monitoring bacterial community of human gut microbiota reveals an increase in Lactobacillus in obese patients and Methanogens in anorexic patients. PLoS One, 2009, 4(9), e7125.
49. Derrien, M.; Vaughan, E.E.; Plugge, C.M.; de Vos, W.M. Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium. Int. J. Syst. Evol. Microbiol., 2004, 54(Pt 5), 1469-1476.
50. Santacruz, A.; Collado, M.C.; García-Valdés, L.; Segura, M.T.; Martín-Lagos, J.A.; Anjos, T.; Martí-Romero, M.; Lopez, R.M.; Florido, J.; Campoy, C.; Sanz, Y. Gut microbiota composition is associated with body weight, weight gain and biochemical parameters in pregnant women. Br. J. Nutr., 2010, 104(1), 83-92.
51. Karlsson, C.L.; Onnerfält, J.; Xu, J.; Molin, G.; Ahrné, S.; Thorngren-Jerneck, K. The microbiota of the gut in preschool children with normal and excessive body weight. Obesity (Silver Spring), 2012, 20(11), 2257-2261.
52. 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. USA, 2013, 110(22), 9066-9071.
53. Plovier, H.; Everard, A.; Druart, C.; Depommier, C.; Van Hul, M.; Geurts, L.; Chilloux, J.; Ottman, N.; Duparc, T.; Lichtenstein, L.; Myridakis, A.; Delzenne, N.M.; Klievink, J.; Bhattacharjee, A.; van der Ark, K.C.; Aalvink, S.; Martinez, L.O.; Dumas, M.E.; Maiter, D.; Loumaye, A.; Hermans, M.P.; Thissen, J.P.; Belzer, C.; de Vos, W.M.; Cani, P.D. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat. Med., 2017, 23(1), 107-113.
54. Dao, M.C.; Everard, A.; Aron-Wisnewsky, J.; Sokolovska, N.; Prifti, E.; Verger, E.O.; Kayser, B.D.; Levenez, F.; Chilloux, J.; Hoyles, L.; Dumas, M.E.; Rizkalla, S.W.; Doré, J.; Cani, P.D.; Clément, K. Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut, 2016, 65(3), 426-436.
55. Ianiro, G.; Tilg, H.; Gasbarrini, A. Antibiotics as deep modulators of gut microbiota: Between good and evil. Gut, 2016, 65(11), 1906-1915.
56. Reijnders, D.; Goossens, G.H.; Hermes, G.D.; Neis, E.P.; van der Beek, C.M.; Most, J.; Holst, J.J.; Lenaerts, K.; Kootte, R.S.; Nieuwdorp, M.; Groen, A.K.; Olde Damink, S.W.; Boekschoten, M.V.; Smidt, H.; Zoetendal, E.G.; De-jong, C.H.; Blaak, E.E. Effects of gut microbiota manipulation by antibiotics on host metabolism in obese humans: A randomized double-blind placebo-controlled trial. Cell Metab., 2016, 24(2), 341.
57. Bailey, L.C.; Forrest, C.B.; Zhang, P.; Richards, T.M.; Livshits, A.; DeRusso, P.A. Association of antibiotics in infancy with early childhood obesity. JAMA Pediatr., 2014, 168(11), 1063-1069.
58. Scott, F.I.; Horton, D.B.; Mamtani, R.; Haynes, K.; Goldberg, D.S.; Lee, D.Y.; Lewis, J.D. Administration of antibiotics to children before age 2 years increases risk for childhood obesity. Gastroenterology, 2016, 151(1), 120-129.
59. Cox, L.M.; Yamanishi, S.; Sohn, J.; Alekseyenko, A.V.; Leung, J.M.; Cho, I.; Kim, S.G.; Li, H.; Gao, Z.; Mahana, D.; Zárate Rodriguez, J.G.; Rogers, A.B.; Robine, N.; Loke, P.; Blaser, M.J. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell, 2014, 158(4), 705-721.
60. Cammarota, G.; Ianiro, G.; Tilg, H.; Rajilić-Stojanović, M.; Kump, P.; Satokari, R.; Sokol, H.; Arkkila, P.; Pintus, C.; Hart, A.; Segal, J.; Aloi, M.; Masucci, L.; Molinaro, A.; Scaldaferri, F.; Gasbarrini, G.; Lopez-Sanroman, A.; Link, A.; de Groot, P.; de Vos, W.M.; Högenauer, C.; Mal-fertheiner, P.; Mattila, E.; Milosavljević, T.; Nieuwdorp, M.; Sanguinetti, M.; Simren, M.; Gasbarrini, A.; European, F.M. European consensus conference on faecal microbiota transplantation in clinical practice. Gut, 2017, 66(4), 569-580.
61. Alang, N.; Kelly, C.R. Weight gain after fecal microbiota transplantation. Open Forum Infect. Dis., 2015, 2(1), ofv004.
62. Ott, S.J.; Waetzig, G.H.; Rehman, A.; Moltzau-Anderson, J.; Bharti, R.; Grasis, J.A.; Cassidy, L.; Tholey, A.; Ficken-scher, H.; Seegert, D.; Rosenstiel, P.; Schreiber, S., Efficacy of Sterile Fecal Filtrate Transfer for Treating Patients With Clostridium difficile Infection. Gastroenterology, 2017, 152, (4), 799-811 e797.
63. Larsen, N.; Vogensen, F.K.; van den Berg, F.W.; Nielsen, D.S.; Andreasen, A.S.; Pedersen, B.K.; Al-Soud, W.A.; Sørensen, S.J.; Hansen, L.H.; Jakobsen, M. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS One, 2010, 5(2), e9085.
64. Qin, J.; Li, Y.; Cai, Z.; Li, S.; Zhu, J.; Zhang, F.; Liang, S.; Zhang, W.; Guan, Y.; Shen, D.; Peng, Y.; Zhang, D.; Jie, Z.; Wu, W.; Qin, Y.; Xue, W.; Li, J.; Han, L.; Lu, D.; Wu, P.; Dai, Y.; Sun, X.; Li, Z.; Tang, A.; Zhong, S.; Li, X.; Chen, W.; Xu, R.; Wang, M.; Feng, Q.; Gong, M.; Yu, J.; Zhang, Y.; Zhang, M.; Hansen, T.; Sanchez, G.; Raes, J.; Falony, G.; Okuda, S.; Almeida, M.; LeChatelier, E.; Renault, P.; Pons, N.; Batto, J.M.; Zhang, Z.; Chen, H.; Yang, R.; Zheng, W.; Li, S.; Yang, H.; Wang, J.; Ehrlich, S.D.; Nielsen, R.; Pedersen, O.; Kristiansen, K.; Wang, J. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature, 2012, 490(7418), 55-60.
65. Karlsson, F.H.; Tremaroli, V.; Nookaew, I.; Bergström, G.; Behre, C.J.; Fagerberg, B.; Nielsen, J.; Bäckhed, F. Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature, 2013, 498(7452), 99-103.
66. Wellen, K.E.; Hotamisligil, G.S. Inflammation, stress, and diabetes. J. Clin. Invest., 2005, 115(5), 1111-1119.
67. Cani, P.D.; Amar, J.; Iglesias, M.A.; Poggi, M.; Knauf, C.; Bastelica, D.; Neyrinck, A.M.; Fava, F.; Tuohy, K.M.; Chabo, C.; Waget, A.; Delmée, E.; Cousin, B.; Sulpice, T.; Chamontin, B.; Ferrières, J.; Tanti, J.F.; Gibson, G.R.; Casteilla, L.; Delzenne, N.M.; Alessi, M.C.; Burcelin, R. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes, 2007, 56(7), 1761-1772.
68. Cani, P.D.; Bibiloni, R.; Knauf, C.; Waget, A.; Neyrinck, A.M.; Delzenne, N.M.; Burcelin, R. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes, 2008, 57(6), 1470-1481.
69. Lu, Y.C.; Yeh, W.C.; Ohashi, P.S. LPS/TLR4 signal transduction pathway. Cytokine, 2008, 42(2), 145-151.
70. Gomes, J.M.; Costa, J.A.; Alfenas, R.C. Metabolic endotoxemia and diabetes mellitus: A systematic review. Metabolism, 2017, 68, 133-144.
71. Sato, J.; Kanazawa, A.; Ikeda, F.; Yoshihara, T.; Goto, H.; Abe, H.; Komiya, K.; Kawaguchi, M.; Shimizu, T.; Ogihara, T.; Tamura, Y.; Sakurai, Y.; Yamamoto, R.; Mita, T.; Fujitani, Y.; Fukuda, H.; Nomoto, K.; Takahashi, T.; Asahara, T.; Hirose, T.; Nagata, S.; Yamashiro, Y.; Watada, H. Gut dysbiosis and detection of “live gut bacteria” in blood of Japanese patients with type 2 diabetes. Diabetes Care, 2014, 37(8), 2343-2350.
72. Gerova, V.A.; Stoynov, S.G.; Katsarov, D.S.; Svinarov, D.A. Increased intestinal permeability in inflammatory bowel diseases assessed by iohexol test. World J. Gastroenterol., 2011, 17(17), 2211-2215.
73. Furusawa, Y.; Obata, Y.; Fukuda, S.; Endo, T.A.; Nakato, G.; Takahashi, D.; Nakanishi, Y.; Uetake, C.; Kato, K.; Kato, T.; Takahashi, M.; Fukuda, N.N.; Murakami, S.; Miyauchi, E.; Hino, S.; Atarashi, K.; Onawa, S.; Fujimura, Y.; Lockett, T.; Clarke, J.M.; Topping, D.L.; Tomita, M.; Hori, S.; Ohara, O.; Morita, T.; Koseki, H.; Kikuchi, J.; Honda, K.; Hase, K.; Ohno, H. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature, 2013, 504(7480), 446-450.
74. Kawano, Y.; Nakae, J.; Watanabe, N.; Kikuchi, T.; Tateya, S.; Tamori, Y.; Kaneko, M.; Abe, T.; Onodera, M.; Itoh, H. Colonic pro-inflammatory macrophages cause insulin resistance in an intestinal Ccl2/Ccr2-dependent manner. Cell Metab., 2016, 24(2), 295-310.
75. Bodinham, C.L.; Smith, L.; Thomas, E.L.; Bell, J.D.; Swann, J.R.; Costabile, A.; Russell-Jones, D.; Umpleby, A.M.; Robertson, M.D. Efficacy of increased resistant starch consumption in human type 2 diabetes. Endocr. Connect., 2014, 3(2), 75-84.
76. Nilsson, A.; Granfeldt, Y.; Ostman, E.; Preston, T.; Björck, I. Effects of GI and content of indigestible carbohydrates of cereal-based evening meals on glucose tolerance at a subsequent standardised breakfast. Eur. J. Clin. Nutr., 2006, 60(9), 1092-1099.
77. Kovatcheva-Datchary, P.; Nilsson, A.; Akrami, R.; Lee, Y.S.; De Vadder, F.; Arora, T.; Hallen, A.; Martens, E.; Björck, I.; Bäckhed, F. Dietary fiber-induced improvement in glucose metabolism is associated with increased abundance of prevotella. Cell Metab., 2015, 22(6), 971-982.
78. Lampe, J.W.; Navarro, S.L.; Hullar, M.A.; Shojaie, A. Inter-individual differences in response to dietary intervention: integrating omics platforms towards personalised dietary recommendations. Proc. Nutr. Soc., 2013, 72(2), 207-218.
79. Korpela, K.; Flint, H.J.; Johnstone, A.M.; Lappi, J.; Poutanen, K.; Dewulf, E.; Delzenne, N.; de Vos, W.M.; Sa-lonen, A. Gut microbiota signatures predict host and microbiota responses to dietary interventions in obese individuals. PLoS One, 2014, 9(6), e90702.
80. Asemi, Z.; Zare, Z.; Shakeri, H.; Sabihi, S.S.; Esmaillzadeh, A. Effect of multispecies probiotic supplements on metabolic profiles, hs-CRP, and oxidative stress in patients with type 2 diabetes. Ann. Nutr. Metab., 2013, 63(1-2), 1-9.
81. Yin, Y.N.; Yu, Q.F.; Fu, N.; Liu, X.W.; Lu, F.G. Effects of four Bifidobacteria on obesity in high-fat diet induced rats. World J. Gastroenterol., 2010, 16(27), 3394-3401.
82. Vrieze, A.; Van Nood, E.; Holleman, F.; Salojarvi, J.; Kootte, R.S.; Bartelsman, J.F.; Dallinga-Thie, G.M.; Ack-ermans, M.T.; Serlie, M.J.; Oozeer, R.; Derrien, M.; Druesne, A.; Van Hylckama Vlieg, J.E.; Bloks, V.W.; Groen, A.K.; Heilig, H.G. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology, 2012, 143(4), 913-916 e917.
83. Zhou, G.; Myers, R.; Li, Y.; Chen, Y.; Shen, X.; Fenyk-Melody, J.; Wu, M.; Ventre, J.; Doebber, T.; Fujii, N.; Musi, N.; Hirshman, M.F.; Goodyear, L.J.; Moller, D.E. Role of AMP-activated protein kinase in mechanism of metformin action. J. Clin. Invest., 2001, 108(8), 1167-1174.
84. Shaw, R.J.; Lamia, K.A.; Vasquez, D.; Koo, S.H.; Bardeesy, N.; Depinho, R.A.; Montminy, M.; Cantley, L.C. The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science, 2005, 310(5754), 1642-1646.
85. Madiraju, A.K.; Erion, D.M.; Rahimi, Y.; Zhang, X.M.; Braddock, D.T.; Albright, R.A.; Prigaro, B.J.; Wood, J.L.; Bhanot, S.; MacDonald, M.J.; Jurczak, M.J.; Camporez, J.P.; Lee, H.Y.; Cline, G.W.; Samuel, V.T.; Kibbey, R.G.; Shulman, G.I. Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. Nature, 2014, 510(7506), 542-546.
86. Forslund, K.; Hildebrand, F.; Nielsen, T.; Falony, G.; Le Chatelier, E.; Sunagawa, S.; Prifti, E.; Vieira-Silva, S.; Gudmundsdottir, V.; Pedersen, H.K.; Arumugam, M.; Kristiansen, K.; Voigt, A.Y.; Vestergaard, H.; Hercog, R.; Costea, P.I.; Kultima, J.R.; Li, J.; Jørgensen, T.; Levenez, F.; Dore, J.; Nielsen, H.B.; Brunak, S.; Raes, J.; Hansen, T.; Wang, J.; Ehrlich, S.D.; Bork, P.; Pedersen, O.; Pedersen, O. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature, 2015, 528(7581), 262-266.
87. Wu, H.; Esteve, E.; Tremaroli, V.; Khan, M.T.; Caesar, R.; Mannerås-Holm, L.; Ståhlman, M.; Olsson, L.M.; Serino, M.; Planas-Fèlix, M.; Xifra, G.; Mercader, J.M.; Torrents, D.; Burcelin, R.; Ricart, W.; Perkins, R.; Fernàndez-Real, J.M.; Bäckhed, F. Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. Nat. Med., 2017, 23(7), 850-858.
88. Luck, H.; Tsai, S.; Chung, J.; Clemente-Casares, X.; Ghazarian, M.; Revelo, X.S.; Lei, H.; Luk, C.T.; Shi, S.Y.; Surendra, A.; Copeland, J.K.; Ahn, J.; Prescott, D.; Rasmussen, B.A.; Chng, M.H.; Engleman, E.G.; Girardin, S.E.; Lam, T.K.; Croitoru, K.; Dunn, S.; Philpott, D.J.; Guttman, D.S.; Woo, M.; Winer, S.; Winer, D.A. Regulation of obesity-related insulin resistance with gut anti-inflammatory agents. Cell Metab., 2015, 21(4), 527-542.
89. Vernon, G.; Baranova, A.; Younossi, Z.M. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment. Pharmacol. Ther., 2011, 34(3), 274-285.
90. Younossi, Z.M.; Stepanova, M.; Afendy, M.; Fang, Y.; Younossi, Y.; Mir, H.; Srishord, M. Changes in the prevalence of the most common causes of chronic liver diseases in the United States from 1988 to 2008. Clin. Gastroenterol. Hepatol., 2011, 9(6), 524-530.
91. Hashimoto, E.; Taniai, M.; Tokushige, K. Characteristics and diagnosis of NAFLD/NASH. J. Gastroenterol. Hepatol., 2013, 28(Suppl. 4), 64-70.
92. Lazo, M.; Solga, S.F.; Horska, A.; Bonekamp, S.; Diehl, A.M.; Brancati, F.L.; Wagenknecht, L.E.; Pi-Sunyer, F.X.; Kahn, S.E.; Clark, J.M. Effect of a 12-month intensive lifestyle intervention on hepatic steatosis in adults with type 2 diabetes. Diabetes Care, 2010, 33(10), 2156-2163.
93. Rafiq, N.; Younossi, Z.M. Effects of weight loss on nonalcoholic fatty liver disease. Semin. Liver Dis., 2008, 28(4), 427-433.
94. Mouzaki, M.; Comelli, E.M.; Arendt, B.M.; Bonengel, J.; Fung, S.K.; Fischer, S.E.; McGilvray, I.D.; Allard, J.P. Intestinal microbiota in patients with nonalcoholic fatty liver disease. Hepatology, 2013, 58(1), 120-127.
95. Zhu, L.; Baker, S.S.; Gill, C.; Liu, W.; Alkhouri, R.; Baker, R.D.; Gill, S.R. Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: a connection between endogenous alcohol and NASH. Hepatology, 2013, 57(2), 601-609.
96. Michail, S.; Lin, M.; Frey, M.R.; Fanter, R.; Paliy, O.; Hilbush, B.; Reo, N.V. Altered gut microbial energy and metabolism in children with non-alcoholic fatty liver disease. FEMS Microbiol. Ecol., 2015, 91(2), 1-9.
97. Le Roy, T.; Llopis, M.; Lepage, P.; Bruneau, A.; Rabot, S.; Bevilacqua, C.; Martin, P.; Philippe, C.; Walker, F.; Bado, A.; Perlemuter, G.; Cassard-Doulcier, A.M.; Gérard, P. Intestinal microbiota determines development of non-alcoholic fatty liver disease in mice. Gut, 2013, 62(12), 1787-1794.
98. Abu-Shanab, A.; Quigley, E.M. The role of the gut microbiota in nonalcoholic fatty liver disease. Nat. Rev. Gastroenterol. Hepatol., 2010, 7(12), 691-701.
99. Jiang, W.; Wu, N.; Wang, X.; Chi, Y.; Zhang, Y.; Qiu, X.; Hu, Y.; Li, J.; Liu, Y. Dysbiosis gut microbiota associated with inflammation and impaired mucosal immune function in intestine of humans with non-alcoholic fatty liver disease. Sci. Rep., 2015, 5, 8096.
100. 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), 1877-1887.
101. Verdam, F.J.; Rensen, S.S.; Driessen, A.; Greve, J.W.; Buurman, W.A. Novel evidence for chronic exposure to endotoxin in human nonalcoholic steatohepatitis. J. Clin. Gastroenterol., 2011, 45(2), 149-152.
102. Sarkola, T.; Eriksson, C.J. Effect of 4-methylpyrazole on endogenous plasma ethanol and methanol levels in humans. Alcohol. Clin. Exp. Res., 2001, 25(4), 513-516.
103. Blomstrand, R. Observations of the formation of ethanol in the intestinal tract in man. Life Sci. II., 1971, 10(10), 575-582.
104. Parlesak, A.; Schäfer, C.; Schütz, T.; Bode, J.C.; Bode, C. Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol-induced liver disease. J. Hepatol., 2000, 32(5), 742-747.
105. Kirsch, R.; Clarkson, V.; Verdonk, R.C.; Marais, A.D.; Shephard, E.G.; Ryffel, B.; de la M Hall, P. Rodent nutritional model of steatohepatitis: effects of endotoxin (lipopolysaccharide) and tumor necrosis factor alpha deficiency. J. Gastroenterol. Hepatol., 2006, 21(1 Pt 1), 174-182.
106. Zeisel, S.H.; daCosta, K.A.; Youssef, M.; Hensey, S. Conversion of dietary choline to trimethylamine and dimethy-lamine in rats: dose-response relationship. J. Nutr., 1989, 119(5), 800-804.
107. Spencer, M.D.; Hamp, T.J.; Reid, R.W.; Fischer, L.M.; Zeisel, S.H.; Fodor, A.A. Association between composition of the human gastrointestinal microbiome and development of fatty liver with choline deficiency. Gastroenterology, 2011, 140(3), 976-986.
108. Porez, G.; Prawitt, J.; Gross, B.; Staels, B. Bile acid receptors as targets for the treatment of dyslipidemia and cardiovascular disease. J. Lipid Res., 2012, 53(9), 1723-1737.
109. Jiao, Y.; Lu, Y.; Li, X.Y. Farnesoid X receptor: a master regulator of hepatic triglyceride and glucose homeostasis. Acta Pharmacol. Sin., 2015, 36(1), 44-50.
110. Watanabe, M.; Houten, S.M.; Mataki, C.; Christoffolete, M.A.; Kim, B.W.; Sato, H.; Messaddeq, N.; Harney, J.W.; Ezaki, O.; Kodama, T.; Schoonjans, K.; Bianco, A.C.; Auwerx, J. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature, 2006, 439(7075), 484-489.
111. Thomas, C.; Gioiello, A.; Noriega, L.; Strehle, A.; Oury, J.; Rizzo, G.; Macchiarulo, A.; Yamamoto, H.; Mataki, C.; Pruzanski, M.; Pellicciari, R.; Auwerx, J.; Schoonjans, K. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab., 2009, 10(3), 167-177.
112. Keitel, V.; Häussinger, D. Perspective: TGR5 (Gpbar-1) in liver physiology and disease. Clin. Res. Hepatol. Gastroenterol., 2012, 36(5), 412-419.
113. Mouzaki, M.; Wang, A.Y.; Bandsma, R.; Comelli, E.M.; Arendt, B.M.; Zhang, L.; Fung, S.; Fischer, S.E.; McGilvray, I.G.; Allard, J.P. Bile acids and dysbiosis in non-alcoholic fatty liver disease. PLoS One, 2016, 11(5), e0151829.
114. Neuschwander-Tetri, B.A.; Loomba, R.; Sanyal, A.J.; Lav-ine, J.E.; Van Natta, M.L.; Abdelmalek, M.F.; Chalasani, N.; Dasarathy, S.; Diehl, A.M.; Hameed, B.; Kowdley, K.V.; McCullough, A.; Terrault, N.; Clark, J.M.; Tonascia, J.; Brunt, E.M.; Kleiner, D.E.; Doo, E. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): A multicentre, randomised, placebo-controlled trial. Lancet, 2015, 385(9972), 956-965.
115. Ritze, Y.; Bárdos, G.; Claus, A.; Ehrmann, V.; Bergheim, I.; Schwiertz, A.; Bischoff, S.C. Lactobacillus rhamnosus GG protects against non-alcoholic fatty liver disease in mice. PLoS One, 2014, 9(1), e80169.
116. Okubo, H.; Sakoda, H.; Kushiyama, A.; Fujishiro, M.; Nakatsu, Y.; Fukushima, T.; Matsunaga, Y.; Kamata, H.; Asahara, T.; Yoshida, Y.; Chonan, O.; Iwashita, M.; Nishimura, F.; Asano, T. Lactobacillus casei strain Shirota protects against nonalcoholic steatohepatitis development in a rodent model. Am. J. Physiol. Gastrointest. Liver Physiol., 2013, 305(12), 911-918.
117. Ma, Y.Y.; Li, L.; Yu, C.H.; Shen, Z.; Chen, L.H.; Li, Y.M. Effects of probiotics on nonalcoholic fatty liver disease: a meta-analysis. World J. Gastroenterol., 2013, 19(40), 6911-6918.
118. Bergheim, I.; Weber, S.; Vos, M.; Krämer, S.; Volynets, V.; Kaserouni, S.; McClain, C.J.; Bischoff, S.C. Antibiotics protect against fructose-induced hepatic lipid accumulation in mice: role of endotoxin. J. Hepatol., 2008, 48(6), 983-992.
119. 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.
120. Madrid, A.M.; Hurtado, C.; Venegas, M.; Cumsille, F.; Defilippi, C. Long-Term treatment with cisapride and antibiotics in liver cirrhosis: effect on small intestinal motility, bacterial overgrowth, and liver function. Am. J. Gastroenterol., 2001, 96(4), 1251-1255.
121. Soza, A.; Riquelme, A.; González, R.; Alvarez, M.; Pérez-Ayuso, R.M.; Glasinovic, J.C.; Arrese, M. Increased oroce-cal transit time in patients with nonalcoholic fatty liver disease. Dig. Dis. Sci., 2005, 50(6), 1136-1140.
122. Do, T.T.; Hindlet, P.; Waligora-Dupriet, A.J.; Kapel, N.; Neveux, N.; Mignon, V.; Deloménie, C.; Farinotti, R.; Fève, B.; Buyse, M. Disturbed intestinal nitrogen homeostasis in a mouse model of high-fat diet-induced obesity and glucose intolerance. Am. J. Physiol. Endocrinol. Metab., 2014, 306(6), 668-680.
123. Okubo, H.; Nakatsu, Y.; Sakoda, H.; Kushiyama, A.; Fujishiro, M.; Fukushima, T.; Matsunaga, Y.; Ohno, H.; Yoneda, M.; Kamata, H.; Shinjo, T.; Iwashita, M.; Nishimura, F.; Asano, T. Mosapride citrate improves nonalcoholic steatohepatitis with increased fecal lactic acid bacteria and plasma glucagon-like peptide-1 level in a rodent model. Am. J. Physiol. Gastrointest. Liver Physiol., 2015, 308(2), G151-G158.
124. Wigg, A.J.; Roberts-Thomson, I.C.; Dymock, R.B.; McCarthy, P.J.; Grose, R.H.; Cummins, A.G. The role of small intestinal bacterial overgrowth, intestinal permeability, endotoxaemia, and tumour necrosis factor alpha in the pathogenesis of non-alcoholic steatohepatitis. Gut, 2001, 48(2), 206-211.
125. He, W.; Wang, M.L.; Jiang, H.Q.; Steppan, C.M.; Shin, M.E.; Thurnheer, M.C.; Cebra, J.J.; Lazar, M.A.; Wu, G.D. Bacterial colonization leads to the colonic secretion of RELMbeta/FIZZ2, a novel goblet cell-specific protein. Gastroenterology, 2003, 125(5), 1388-1397.
126. Kushiyama, A.; Sakoda, H.; Oue, N.; Okubo, M.; Nakatsu, Y.; Ono, H.; Fukushima, T.; Kamata, H.; Nishimura, F.; Kikuchi, T.; Fujishiro, M.; Nishiyama, K.; Aburatani, H.; Kushiyama, S.; Iizuka, M.; Taki, N.; Encinas, J.; Sentani, K.; Ogonuki, N.; Ogura, A.; Kawazu, S.; Yasui, W.; Higashi, Y.; Kurihara, H.; Katagiri, H.; Asano, T. Resistin-like molecule β is abundantly expressed in foam cells and is involved in atherosclerosis development. Arterioscler. Thromb. Vasc. Biol., 2013, 33(8), 1986-1993.
127. Hildebrandt, M.A.; Hoffmann, C.; Sherrill-Mix, S.A.; Keilbaugh, S.A.; Hamady, M.; Chen, Y.Y.; Knight, R.; Ahima, R.S.; Bushman, F.; Wu, G.D. High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology, 2009, 137(5), 1716-1724. e1711-1712
128. Nair, M.G.; Guild, K.J.; Du, Y.; Zaph, C.; Yancopoulos, G.D.; Valenzuela, D.M.; Murphy, A.; Stevens, S.; Karow, M.; Artis, D. Goblet cell-derived resistin-like molecule beta augments CD4+ T cell production of IFN-gamma and in-fection-induced intestinal inflammation. J. Immunol., 2008, 181(7), 4709-4715.
129. McVay, L.D.; Keilbaugh, S.A.; Wong, T.M.; Kierstein, S.; Shin, M.E.; Lehrke, M.; Lefterova, M.I.; Shifflett, D.E.; Barnes, S.L.; Cominelli, F.; Cohn, S.M.; Hecht, G.; Lazar, M.A.; Haczku, A.; Wu, G.D. Absence of bacterially induced RELMbeta reduces injury in the dextran sodium sulfate model of colitis. J. Clin. Invest., 2006, 116(11), 2914-2923.
130. Kushiyama, A.; Shojima, N.; Ogihara, T.; Inukai, K.; Sakoda, H.; Fujishiro, M.; Fukushima, Y.; Anai, M.; Ono, H.; Horike, N.; Viana, A.Y.; Uchijima, Y.; Nishiyama, K.; Shimosawa, T.; Fujita, T.; Katagiri, H.; Oka, Y.; Kurihara, H.; Asano, T. Resistin-like molecule beta activates MAPKs, suppresses insulin signaling in hepatocytes, and induces diabetes, hyperlipidemia, and fatty liver in transgenic mice on a high fat diet. J. Biol. Chem., 2005, 280(51), 42016-42025.
131. Okubo, H.; Kushiyama, A.; Sakoda, H.; Nakatsu, Y.; Iizuka, M.; Taki, N.; Fujishiro, M.; Fukushima, T.; Kamata, H.; Nagamachi, A.; Inaba, T.; Nishimura, F.; Katagiri, H.; Asahara, T.; Yoshida, Y.; Chonan, O.; Encinas, J.; Asano, T. Involvement of resistin-like molecule β in the development of methionine-choline deficient diet-induced non-alcoholic steatohepatitis in mice. Sci. Rep., 2016, 6, 20157.
132. Neilson, A.P.; Djuric, Z.; Land, S.; Kato, I. Plasma levels of resistin-like molecule beta in humans. Cancer Epidemiol., 2011, 35(5), 485-489.