The role of the gut microbiota in metabolic health

FASEB Journal

Volumn 29, Issue 8, 2015, Pages 3111-3123

  Janssen, Aafke W F ^a   Kersten, Sander ^a  

^a WAGENINGEN UNIVERSITY   (Netherlands)

Author keywords

Energy harvest; Gut permeability; Insulin resistance; Obesity; Short chain fatty acids

Indexed keywords

CHOLINE; SHORT CHAIN FATTY ACID;

ANGPTL4 GENE; BILE ACID METABOLISM; DIET; GENE; GENOME; HEALTH; HUMAN; INTESTINE FLORA; INTESTINE MUCOSA PERMEABILITY; META ANALYSIS (TOPIC); METABOLIC DISORDER; METABOLIC HEALTH; METABOLISM; NONHUMAN; OBESITY; PRIORITY JOURNAL; REVIEW; ANIMAL; GASTROINTESTINAL TRACT; METABOLIC DISEASES; MICROBIOLOGY; MICROFLORA; PHYSIOLOGY;

MUS;

ANIMALS; GASTROINTESTINAL TRACT; HUMANS; METABOLIC DISEASES; MICROBIOTA; OBESITY;

EID: 84940392207     PISSN: 08926638     EISSN: 15306860     Source Type: Journal    
DOI: 10.1096/fj.14-269514     Document Type: Review

References (120)

1. Ng, M., Fleming, T., Robinson, M., Thomson, B., Graetz, N., Margono, C., Mullany, E. C., Biryukov, S., Abbafati, C., Abera, S. F., Abraham, J. P., Abu-Rmeileh, N. M., Achoki, T., AlBuhairan, F. S., Alemu, Z. A., Alfonso, R., Ali, M. K., Ali, R., Guzman, N. A., Ammar, W., Anwari, P., Banerjee, A., Barquera, S., Basu, S., Bennett, D. A., Bhutta, Z., Blore, J., Cabral, N., Nonato, I. C., Chang, J. C., Chowdhury, R., Courville, K. J., Criqui, M. H., Cundiff, D. K., Dabhadkar, K. C., Dandona, L., Davis, A., Dayama, A., Dharmaratne, S. D., Ding, E. L., Durrani, A. M., Esteghamati, A., Farzadfar, F., Fay, D. F., Feigin, V. L., Flaxman, A., Forouzanfar, M. H., Goto, A., Green, M. A., Gupta, R., Hafezi-Nejad, N., Hankey, G. J., Harewood, H. C., Havmoeller, R., Hay, S., Hernandez, L., Husseini, A., Idrisov, B. T., Ikeda, N., Islami, F., Jahangir, E., Jassal, S. K., Jee, S. H., Jeffreys, M., Jonas, J.B., Kabagambe, E. K., Khalifa, S. E., Kengne, A. P., Khader, Y. S., Khang, Y. H., Kim, D., Kimokoti, R. W., Kinge, J.M., Kokubo, Y., Kosen, S., Kwan, G., Lai, T., Leinsalu, M., Li, Y., Liang, X., Liu, S., Logroscino, G., Lotufo, P.A., Lu, Y., Ma, J., Mainoo, N. K., Mensah, G. A., Merriman, T. R., Mokdad, A. H., Moschandreas, J., Naghavi, M., Naheed, A., Nand, D., Narayan, K.M., Nelson, E.L., Neuhouser, M. L., Nisar, M. I., Ohkubo, T., Oti, S. O., Pedroza, A., Prabhakaran, D., Roy, N., Sampson, U., Seo, H., Sepanlou, S. G., Shibuya, K., Shiri, R., Shiue, I., Singh, G.M., Singh, J. A., Skirbekk, V., Stapelberg, N. J., Sturua, L., Sykes, B. L., Tobias, M., Tran, B. X., Trasande, L., Toyoshima, H., van de Vijver, S., Vasankari, T. J., Veerman, J. L., Velasquez-Melendez, G., Vlassov, V. V., Vollset, S. E., Vos, T., Wang, C., Wang, X., Weiderpass, E., Werdecker, A., Wright, J. L., Yang, Y. C., Yatsuya, H., Yoon, J., Yoon, S. J., Zhao, Y., Zhou, M., Zhu, S., Lopez, A. D., Murray, C. J., and Gakidou, E. (2014) Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: A systematic analysis for the Global Burden of Disease Study 2013. Lancet 384, 766-781.
2. Matheus, A. S., Tannus, L. R., Cobas, R. A., Palma, C. C., Negrato, C. A., and Gomes, M. B. (2013) Impact of diabetes on cardiovascular disease: An update. Int. J. Hypertens. 2013, 653789.
3. Despŕes, J. P., Lemieux, I., Bergeron, J., Pibarot, P., Mathieu, P., Larose, E., Rodés-Cabau, J., Bertrand, O. F., and Poirier, P. (2008) Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk. Arterioscler. Thromb. Vasc. Biol. 28, 1039-1049.
4. Pi-Sunyer, X. (2009)Themedical risks ofobesity.Postgrad.Med. 121, 21-33.
5. D'Aversa, F., Tortora, A., Ianiro, G., Ponziani, F. R., Annicchiarico, B. E., and Gasbarrini, A. (2013) Gut microbiota and metabolic syndrome. Intern. Emerg. Med. 8(Suppl 1), S11-S15.
6. Kau, A. L., Ahern, P. P., Griffin, N. W., Goodman, A. L., and Gordon, J. I. (2011)Human nutrition, the gutmicrobiome and the immune system. Nature 474, 327-336.
7. De Wit, N., Derrien, M., Bosch-Vermeulen, H., Oosterink, E., Keshtkar, S., Duval, C., de Vogel-van den Bosch, J., Kleerebezem, M., Müller, M., and van derMeer, R. (2012) Saturated fat stimulates obesityandhepatic steatosis andaffects gutmicrobiota composition by an enhanced overflow of dietary fat to the distal intestine. Am. J. Physiol. Gastrointest. Liver Physiol. 303, G589-G599.
8. Ley, R. E., Bäckhed, F., Turnbaugh, P., Lozupone, C. A., Knight, R.D., and Gordon, J. I. (2005)Obesity alters gutmicrobial ecology. Proc.Natl. Acad. Sci. USA 102, 11070-11075.
9. Turnbaugh, P. J., Bäckhed, F., Fulton, L., and Gordon, J. I. (2008) Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe 3, 213-223.
10. Ley, R. E., Turnbaugh, P. J., Klein, S., and Gordon, J. I. (2006) Microbial ecology: human gut microbes associated with obesity. Nature 444, 1022-1023.
11. Schwiertz, A., Taras, D., Schäfer, K., Beijer, S., Bos, N.A., Donus, C., and Hardt, P. D. (2010) Microbiota and SCFA in lean and overweight healthy subjects. Obesity (Silver Spring) 18, 190-195.
12. Karlsson, F. H., Fak, F., Nookaew, I., Tremaroli, V., Fagerberg, B., Petranovic, D., Bäckhed, F., and Nielsen, J. (2012) Symptomatic atherosclerosis is associated with an altered gut metagenome. Nat. Commun. 3, 1245.
13. 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., and Wang, J. (2012) A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490, 55-60.
14. Jiang, W., Wu, N., Wang, X., Chi, Y., Zhang, Y., Qiu, X., Hu, Y., Li, J., and Liu, Y. (2015) Dysbiosis gut microbiota associated with inflammation and impaired mucosal immune function in intestine of humans with non-alcoholic fatty liver disease. Sci. Rep. 5, 8096.
15. Zhu, L., Baker, S. S., Gill, C., Liu, W., Alkhouri, R., Baker, R. D., and Gill, S.R. (2013) Characterization of gutmicrobiomes in nonalcoholic steatohepatitis (NASH) patients: A connection between endogenous alcohol and NASH. Hepatology 57, 601-609.
16. Clemente, J. C., Ursell, L. K., Parfrey, L. W., and Knight, R. (2012) The impact of the gut microbiota on human health: An integrative view. Cell 148, 1258-1270.
17. Sekirov, I., Russell, S. L., Antunes, L.C., and Finlay, B. B. (2010)Gut microbiota in health and disease. Physiol. Rev. 90, 859-904.
18. Sommer, F., and Bäckhed, F. (2013) The gut microbiota: masters of host development and physiology. Nat. Rev. Microbiol. 11, 227-238.
19. Moschen, A. R., Wieser, V., and Tilg, H. (2012) Dietary factors: major regulators of the gut's microbiota. Gut Liver 6, 411-416.
20. Kinross, J.M., vonRoon, A.C., Holmes, E., Darzi, A., and Nicholson, J. K. (2008) The human gut microbiome: implications for future health care. Curr. Gastroenterol. Rep. 10, 396-403.
21. Qin, J., Li, R., Raes, J., Arumugam, M., Burgdorf, K. S., Manichanh, C., Nielsen, T., Pons, N., Levenez, F., Yamada, T., Mende, D.R., Li, J., Xu, J., Li, S., Li, D., Cao, J., Wang, B., Liang, H., Zheng, H., Xie, Y., Tap, J., Lepage, P., Bertalan, M., Batto, J.M., Hansen, T., Le Paslier, D., Linneberg, A., Nielsen, H. B., Pelletier, E., Renault, P., Sicheritz-Ponten, T., Turner, K., Zhu, H., Yu, C., Li, S., Jian, M., Zhou, Y., Li, Y., Zhang, X., Li, S., Qin, N., Yang, H., Wang, J., Brunak, S., Doŕe, J., Guarner, F., Kristiansen, K., Pedersen, O., Parkhill, J., Weissenbach, J., Bork, P., Ehrlich, S. D., and Wang, J.; MetaHIT Consortium. (2010) A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464, 59-65.
22. Eckburg, P. B., Bik, E.M., Bernstein, C.N., Purdom, E., Dethlefsen, L., Sargent, M., Gill, S. R., Nelson, K. E., and Relman, D.A. (2005)Diversity of the human intestinal microbial flora. Science 308, 1635-1638.
23. Round, J. L., and Mazmanian, S. K. (2009) The gut microbiota shapes intestinal immune responses during healthand disease. Nat. Rev. Immunol. 9, 313-323.
24. Smith, K., McCoy, K.D., and Macpherson, A. J. (2007)Useofaxenic animals in studying the adaptation ofmammals to their commensal intestinal microbiota. Semin. Immunol. 19, 59-69.
25. Wong, J. M., Esfahani, A., Singh, N., Villa, C. R., Mirrahimi, A., Jenkins, D. J., and Kendall, C. W. (2012) Gut microbiota, diet, and heart disease. J. AOAC Int. 95, 24-30.
26. Chassard, C., and Lacroix, C. (2013)Carbohydrates and thehuman gut microbiota. Curr. Opin. Clin. Nutr. Metab. Care 16, 453-460.
27. Louis, P., Scott, K. P., Duncan, S. H., and Flint, H. J. (2007) Understanding the effects of diet on bacterial metabolism in the large intestine. J. Appl. Microbiol. 102, 1197-1208.
28. Tremaroli, V., and Bäckhed, F. (2012) Functional interactions between the gut microbiota and host metabolism. Nature 489, 242-249.
29. Benson, A.K., Kelly, S.A., Legge, R., Ma, F., Low, S. J., Kim, J., Zhang, M., Oh, P.L., Nehrenberg, D., Hua, K., Kachman, S.D., Moriyama, E. N., Walter, J., Peterson, D. A., and Pomp, D. (2010) Individuality in gut microbiota composition is a complex polygenic trait shaped bymultiple environmental and host genetic factors. Proc.Natl.Acad. Sci. USA 107, 18933-18938.
30. Turnbaugh, P. J., Ley, R. E., Hamady, M., Fraser-Liggett, C. M., Knight, R., and Gordon, J. I. (2007) The human microbiome project. Nature 449, 804-810.
31. De Filippo, C., Cavalieri, D., Di Paola, M., Ramazzotti, M., Poullet, J. B., Massart, S., Collini, S., Pieraccini, G., and Lionetti, P. (2010) Impact of diet in shaping gutmicrobiota revealed by a comparative study in children fromEurope and rural Africa. Proc. Natl. Acad. Sci. USA 107, 14691-14696.
32. Wu, G. D., Chen, J., Hoffmann, C., Bittinger, K., Chen, Y. Y., Keilbaugh, S. A., Bewtra, M., Knights, D., Walters, W. A., Knight, R., Sinha, R., Gilroy, E., Gupta, K., Baldassano, R., Nessel, L., Li, H., Bushman, F. D., and Lewis, J. D. (2011) Linking long-term dietary patterns with gut microbial enterotypes. Science 334, 105-108.
33. David, L. A., Maurice, C. F., Carmody, R. N., Gootenberg, D. B., Button, J. E., Wolfe, B. E., Ling, A. V., Devlin, A. S., Varma, Y., Fischbach, M. A., Biddinger, S. B., Dutton, R. J., and Turnbaugh, P. J. (2014) Diet rapidly and reproducibly alters the human gut microbiome. Nature 505, 559-563.
34. Walker, A. W., Ince, J., Duncan, S. H., Webster, L. M., Holtrop, G., Ze, X., Brown, D., Stares, M. D., Scott, P., Bergerat, A., Louis, P., McIntosh, F., Johnstone, A.M., Lobley, G. E., Parkhill, J., and Flint, H. J. (2011) Dominant and diet-responsive groups of bacteria within the human colonic microbiota. ISME J. 5, 220-230.
35. Carmody, R. N., Gerber, G. K., Luevano, J. M. Jr., Gatti, D. M., Somes, L., Svenson, K. L., and Turnbaugh, P. J. (2015) Diet dominateshost genotypeinshaping themurine gutmicrobiota. Cell Host Microbe 17, 72-84.
36. Zimmer, J., Lange, B., Frick, J. S., Sauer, H., Zimmermann, K., Schwiertz, A., Rusch, K., Klosterhalfen, S., and Enck, P. (2012) A vegan or vegetarian diet substantially alters the human colonic faecal microbiota. Eur. J. Clin. Nutr. 66, 53-60.
37. Yan, H., Potu, R., Lu, H., Vezzoni de Almeida, V., Stewart, T., Ragland, D., Armstrong, A., Adeola, O., Nakatsu, C. H., and Ajuwon, K. M. (2013) Dietary fat content and fiber type modulate hind gut microbial community and metabolic markers in the pig. PLoS ONE 8, e59581.
38. Turnbaugh, P. J., Hamady, M., Yatsunenko, T., Cantarel, B. L., Duncan, A., Ley, R.E., Sogin, M.L., Jones, W.J., Roe, B.A., Affourtit, J. P., Egholm, M., Henrissat, B., Heath, A. C., Knight, R., and Gordon, J. I. (2009)Acore gutmicrobiome in obese and leantwins. Nature 457, 480-484.
39. Nicholson, J. K., Holmes, E., Kinross, J., Burcelin, R., Gibson, G., Jia, W., and Pettersson, S. (2012) Host-gut microbiota metabolic interactions. Science 336, 1262-1267.
40. Yi, P., and Li, L. (2012) The germfreemurine animal: An important animal model for research on the relationship between gut microbiota and the host. Vet. Microbiol. 157, 1-7.
41. Turnbaugh, P.J., Ridaura, V.K., Faith, J.J., Rey, F.E., Knight, R., and Gordon, J.I. (2009)Theeffect of dietonthehumangutmicrobiome: Ametagenomic analysis in humanized gnotobiotic mice. Sci. Translat. Med. 1, 6ra14.
42. Goodman, A. L., Kallstrom, G., Faith, J. J., Reyes, A., Moore, A., Dantas, G., and Gordon, J. I. (2011) Extensive personal human gut microbiota culture collections characterized and manipulated in gnotobiotic mice. Proc.Natl. Acad. Sci. USA 108, 6252-6257.
43. Benoit, B., Laugerette, F., Plaisancie, P., Geloen, A., Bodennec, J., Estienne, M., Pineau, G., Bernalier-Donadille, A., Vidal, H., and Michalski, M.C. (2015) Increasing fat content from 20 to 45 wt% in a complexdiet induces lowerendotoxemiainparallelwithanincreased number of intestinal goblet cells in mice. Nutr. Res. 35, 346-356.
44. Mozes, S., Bujńaková, D., Sefćiková, Z., and Kmet, V. (2008) Intestinal microflora and obesity in rats. Folia Microbiol. (Praha) 53, 225-228.
45. Guo, X., Xia, X., Tang, R., Zhou, J., Zhao, H., and Wang, K. (2008) Development of a real-time PCR method for Firmicutes and Bacteroidetes in faeces and its application to quantify intestinal population of obese and lean pigs. Lett. Appl. Microbiol. 47, 367-373.
46. Hildebrandt, M.A., Hoffmann, C., Sherrill-Mix, S.A., Keilbaugh, S.A., Hamady, M., Chen, Y.Y., Knight, R., Ahima, R.S., Bushman, F., and Wu, G.D. (2009) High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology 137, 1716-1724.e1-e2.
47. Murphy, E.F., Cotter, P.D., Healy, S., Marques, T.M., O'Sullivan, O., Fouhy, F., Clarke, S. F., O'Toole, P.W., Quigley, E. M., Stanton, C., Ross, P.R., O'Doherty, R. M., and Shanahan, F. (2010)Composition and energyharvesting capacityof the gutmicrobiota: relationship to diet, obesity and time in mouse models. Gut 59, 1635-1642.
48. Bäckhed, F., Manchester, J.K., Semenkovich, C. F., and Gordon, J. I. (2007) Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc.Natl. Acad. Sci. USA 104, 979-984.
49. Caesar, R., Reigstad, C. S., Bäckhed, H. K., Reinhardt, C., Ketonen, M., Lunden, G.O., Cani, P.D., and Bäckhed, F. (2012)Gut-derived lipopolysaccharide augments adipose macrophage accumulation but is not essential for impaired glucose or insulin tolerance in mice. Gut 61, 1701-1707.
50. Ding, S., Chi, M. M., Scull, B. P., Rigby, R., Schwerbrock, N. M., Magness, S., Jobin, C., and Lund, P. K. (2010) High-fat diet: bacteria interactionspromote intestinal inflammation whichprecedes and correlates with obesity and insulin resistance in mouse. PLoS ONE 5, e12191.
51. Ellekilde, M., Selfjord, E., Larsen, C. S., Jakesevic, M., Rune, I., Tranberg, B., Vogensen, F.K., Nielsen, D. S., Bahl, M. I., Licht, T.R., Hansen, A.K., and Hansen, C.H. (2014)Transfer of gutmicrobiota fromlean and obesemice to antibiotic-treated mice. Sci. Rep. 4, 5922.
52. 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., VanTreuren, W., Walters, W.A., Knight, R., Newgard, C. B., Heath, A. C., and Gordon, J. I. (2013) Gutmicrobiota fromtwins discordant for obesity modulate metabolism in mice. Science 341, 1241214.
53. Murphy, E.F., Cotter, P.D., Hogan, A., O'Sullivan, O., Joyce, A., Fouhy, F., Clarke, S. F., Marques, T. M., O'Toole, P. W., Stanton, C., Quigley, E.M., Daly, C., Ross, P.R., O'Doherty, R. M., and Shanahan, F. (2013) Divergentmetabolic outcomes arising fromtargetedmanipulation of the gut microbiota in diet-induced obesity. Gut 62, 220-226.
54. 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., and Blaser, M. J. (2014) Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell 158, 705-721.
55. Furet, J. P., Kong, L. C., Tap, J., Poitou, C., Basdevant, A., Bouillot, J. L., Mariat, D., Corthier, G., Doŕe, J., Henegar, C., Rizkalla, S., and Cĺement, K. (2010)Differential adaptationof humangutmicrobiota to bariatric surgery-induced weight loss: links with metabolic and low-grade inflammation markers. Diabetes 59, 3049-3057.
56. Zhang, H., DiBaise, J.K., Zuccolo, A., Kudrna, D., Braidotti, M., Yu, Y., Parameswaran, P., Crowell, M.D., Wing, R., Rittmann, B. E., and Krajmalnik-Brown, R. (2009)Human gutmicrobiota in obesity and after gastric bypass. Proc. Natl. Acad. Sci. USA 106, 2365-2370.
57. Duncan, S.H., Lobley, G.E., Holtrop, G., Ince, J., Johnstone, A.M., Louis, P., and Flint, H.J. (2008)Humancolonic microbiota associated with diet, obesity and weight loss. Int. J. Obes. 32, 1720-1724.
58. Liou, A.P., Paziuk, M., Luevano, J.M. Jr, Machineni, S., Turnbaugh, P.J., and Kaplan, L.M. (2013)Conserved shifts in the gutmicrobiota due to gastric bypass reduce host weight and adiposity. Sci. Translat. Med. 5, 178ra41.
59. Crawford, P.A., Crowley, J.R., Sambandam, N., Muegge, B.D., Costello, E. K., Hamady, M., Knight, R., and Gordon, J. I. (2009) Regulation of myocardial ketone body metabolism by the gut microbiota during nutrient deprivation. Proc. Natl. Acad. Sci. USA 106, 11276-11281.
60. Dethlefsen, L., Huse, S., Sogin, M. L., and Relman, D.A. (2008)The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biol. 6, e280.
61. Thuny, F., Richet, H., Casalta, J. P., Angelakis, E., Habib, G., and Raoult, D. (2010)Vancomycintreatment of infective endocarditis is linked with recently acquired obesity. PLoS ONE 5, e9074.
62. Lam, Y. Y., Ha, C. W., Campbell, C. R., Mitchell, A. J., Dinudom, A., Oscarsson, J., Cook, D. I., Hunt, N. H., Caterson, I. D., Holmes, A. J., and Storlien, L. H. (2012) Increased gutpermeability andmicrobiota change associate with mesenteric fat inflammation and metabolic dysfunction in diet-induced obese mice. PLoS ONE 7, e34233.
63. Henao-Mejia, J., Elinav, E., Jin, C., Hao, L., Mehal, W.Z., Strowig, T., Thaiss, C. A., Kau, A. L., Eisenbarth, S. C., Jurczak, M. J., Camporez, J. P., Shulman, G. I., Gordon, J. I., Hoffman, H.M., and Flavell, R.A. (2012) Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 482, 179-185.
64. Dixon, L. J., Flask, C. A., Papouchado, B. G., Feldstein, A. E., and Nagy, L. E. (2013) Caspase-1 as a central regulator of high fat dietinduced non-alcoholic steatohepatitis. PLoS ONE 8, e56100.
65. Peverill, W., Powell, L.W., and Skoien, R. (2014) Evolving concepts in the pathogenesis of NASH: beyond steatosis and inflammation. Int. J. Mol. Sci. 15, 8591-8638.
66. Wree, A., McGeough, M. D., Peña, C. A., Schlattjan, M., Li, H., Inzaugarat, M. E., Messer, K., Canbay, A., Hoffman, H. M., and Feldstein, A. E. (2014)NLRP3 inflammasome activationis required for fibrosis development in NAFLD. J. Mol. Med. 92, 1069-1082.
67. 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., and Gonzalez, F. J. (2015) Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease. J. Clin. Invest. 125, 386-402.
68. Bergheim, I., Weber, S., Vos, M., Krämer, S., Volynets, V., Kaserouni, S., McClain, C. J., and Bischoff, S. C. (2008) Antibiotics protect against fructose-induced hepatic lipid accumulation in mice: role of endotoxin. J. Hepatol. 48, 983-992.
69. Lin, Y., Yu, L. X., Yan, H.X., Yang, W., Tang, L., Zhang, H. L., Liu, Q., Zou, S. S., He, Y. Q., Wang, C., Wu, M. C., and Wang, H. Y. (2012)GutderivedlipopolysaccharidepromotesT- cell-mediated hepatitis inmice through Toll-like receptor 4. Cancer Prev.Res. (Phila.) 5, 1090-1102.
70. Rabot, S., Membrez, M., Bruneau, A., Gerard, P., Harach, T., Moser, M., Raymond, F., Mansourian, R., and Chou, C. J. (2010) Germ-free C57BL/6J mice are resistant to high-fat-diet-induced insulin resistance and have altered cholesterolmetabolism. FASEB J. 24, 4948-4959.
71. Ye, X. Y., Xue, Y.M., Sha, J. P., Li, C. Z., and Zhen, Z. J. (2009) Serum amyloid A attenuates cellular insulin sensitivity by increasing JNK activity in 3T3-L1 adipocytes. J. Endocrinol. Invest. 32, 568-575.
72. Bäckhed, F., Ding, H., Wang, T., Hooper, L. V., Koh, G. Y., Nagy, A., Semenkovich, C. F., and Gordon, J. I. (2004) The gutmicrobiota as an environmental factor that regulates fat storage. Proc. Natl. Acad. Sci. USA 101, 15718-15723.
73. Vrieze, A., Van Nood, E., Holleman, F., Salojarvi, J., Kootte, R.S., Bartelsman, J.F., Dallinga-Thie, G.M., Ackermans, M.T., Serlie, M.J., and Oozeer, R. (2012) Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology 143, 913-916.e7.
74. Pankow, J. S., Duncan, B. B., Schmidt, M. I., Ballantyne, C. M., Couper, D. J., Hoogeveen, R. C., and Golden, S.H.; Atherosclerosis Risk in Communities Study. (2004) Fasting plasma free fatty acids and risk of type 2 diabetes: The atherosclerosis risk in communities study. Diabetes Care 27, 77-82.
75. Membrez, M., Blancher, F., Jaquet, M., Bibiloni, R., Cani, P. D., Burcelin, R. G., Corthesy, I., Maće, K., and Chou, C. J. (2008)Gut microbiota modulation with norfloxacin and ampicillin enhances glucose tolerance in mice. FASEB J. 22, 2416-2426.
76. Turnbaugh, P. J., Ley, R. E., Mahowald, M. A., Magrini, V., Mardis, E. R., and Gordon, J. I. (2006)An obesity-associated gutmicrobiome with increased capacity for energy harvest. Nature 444, 1027-1031.
77. Carvalho, B. M., Guadagnini, D., Tsukumo, D. M., Schenka, A. A., Latuf-Filho, P., Vassallo, J., Dias, J. C., Kubota, L. T., Carvalheira, J. B., and Saad, M. J. (2012) Modulation of gut microbiota by antibiotics improves insulin signalling in high-fat fed mice. Diabetologia 55, 2823-2834.
78. Velagapudi, V.R., Hezaveh, R., Reigstad, C. S., Gopalacharyulu, P., Yetukuri, L., Islam, S., Felin, J., Perkins, R., Boŕen, J., Oresic, M., and Bäckhed, F. (2010) The gutmicrobiotamodulates host energy and lipid metabolism in mice. J. Lipid Res. 51, 1101-1112.
79. Mattijssen, F., Alex, S., Swarts, H. J., Groen, A. K., van Schothorst, E. M., and Kersten, S. (2014) Angptl4 serves as an endogenous inhibitor of intestinal lipid digestion. Mol. Metab. 3, 135-144.
80. 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., Delmee, E., Cousin, B., Sulpice, T., Chamontin, B., Ferrières, J., Tanti, J.F., Gibson, G.R., Casteilla, L., Delzenne, N.M., Alessi, M.C., and Burcelin, R. (2007) Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56, 1761-1772.
81. Pendyala, S., Walker, J.M., and Holt, P.R. (2012) A high-fat diet is associated with endotoxemia that originates from the gut. Gastroenterology 142, 1100-1101.e2.
82. Wellen, K. E., and Hotamisligil, G. S. (2005) Inflammation, stress, and diabetes. J. Clin. Invest. 115, 1111-1119.
83. Cani, P. D., Bibiloni, R., Knauf, C., Waget, A., Neyrinck, A. M., Delzenne, N.M., and Burcelin, R. (2008)Changes in gutmicrobiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 57, 1470-1481.
84. Muccioli, G. G., Naslain, D., Bäckhed, F., Reigstad, C. S., Lambert, D. M., Delzenne, N. M., and Cani, P. D. (2010) The endocannabinoid system links gut microbiota to adipogenesis. Mol. Syst. Biol. 6, 392.
85. Fukunishi, S., Sujishi, T., Takeshita, A., Ohama, H., Tsuchimoto, Y., Asai, A., Tsuda, Y., and Higuchi, K. (2014) Lipopolysaccharides accelerate hepatic steatosis in the development of nonalcoholic fatty liver disease in Zucker rats. J. Clin. Biochem. Nutr. 54, 39-44.
86. Lichtenstein, L., Mattijssen, F., deWit, N. J., Georgiadi, A., Hooiveld, G. J., van der Meer, R., He, Y., Qi, L., Köster, A., Tamsma, J. T., Tan, N. S., Müller, M., and Kersten, S. (2010)Angptl4protects against severe proinflammatory effects of saturated fat by inhibiting fatty acid uptake into mesenteric lymph node macrophages. Cell Metab. 12, 580-592.
87. Laugerette, F., Furet, J.P., Debard, C., Daira, P., Loizon, E., Gelöen, A., Soulage, C. O., Simonet, C., Lefils-Lacourtablaise, J., Bernoud-Hubac, N., Bodennec, J., Peretti, N., Vidal, H., and Michalski, M.C.(2012)Oil composition of high-fat diet affects metabolic inflammation differently in connection with endotoxin receptors inmice. Am. J. Physiol. Endocrinol. Metab. 302, E374-E386.
88. Huang, H., Liu, T., Rose, J.L., Stevens, R. L., and Hoyt, D.G. (2007) Sensitivity of mice to lipopolysaccharide is increased by a high saturated fat and cholesterol diet. J. Inflamm. (Lond.) 4, 22.
89. Schertzer, J. D., Tamrakar, A. K., Magalhães, J.G., Pereira, S., Bilan, P. J., Fullerton, M. D., Liu, Z., Steinberg, G.R., Giacca, A., Philpott, D. J., and Klip, A. (2011) NOD1 activators link innate immunity to insulin resistance. Diabetes 60, 2206-2215.
90. Bergman, E. N. (1990) Energy contributions of volatile fatty acids from the gastrointestinal tract in various species. Physiol. Rev. 70, 567-590.
91. Le Poul, E., Loison, C., Struyf, S., Springael, J. Y., Lannoy, V., Decobecq, M. E., Brezillon, S., Dupriez, V., Vassart, G., VanDamme, J., Parmentier, M., and Detheux, M. (2003) Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J. Biol. Chem. 278, 25481-25489.
92. Nøhr, M. K., Pedersen, M. H., Gille, A., Egerod, K. L., Engelstoft, M. S., Husted, A. S., Sichlau, R. M., Grunddal, K. V., Poulsen, S. S., Han, S., Jones, R. M., Offermanns, S., and Schwartz, T. W. (2013) GPR41/FFAR3 and GPR43/FFAR2 as cosensors for short-chain fatty acids inenteroendocrinecells vs FFAR3 inentericneurons and FFAR2 in enteric leukocytes. Endocrinology 154, 3552-3564.
93. Brown, A. J., Goldsworthy, S. M., Barnes, A. A., Eilert, M. M., Tcheang, L., Daniels, D., Muir, A. I., Wigglesworth, M. J., Kinghorn, I., Fraser, N. J., Pike, N. B., Strum, J. C., Steplewski, K.M., Murdock, P. R., Holder, J.C., Marshall, F.H., Szekeres, P.G., Wilson, S., Ignar, D.M., Foord, S.M., Wise, A., and Dowell, S. J. (2003)TheOrphanG protein-coupled receptors GPR41 and GPR43 are activated by propionate andother short chaincarboxylic acids. J. Biol.Chem. 278, 11312-11319.
94. Samuel, B. S., Shaito, A., Motoike, T., Rey, F. E., Backhed, F., Manchester, J. K., Hammer, R. E., Williams, S. C., Crowley, J., Yanagisawa, M., and Gordon, J. I. (2008) Effectsof thegutmicrobiota on host adiposity aremodulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc. Natl. Acad. Sci. USA 105, 16767-16772.
95. Lin, H. V., Frassetto, A., Kowalik, E. J. Jr., Nawrocki, A.R., Lu, M.M., Kosinski, J. R., Hubert, J. A., Szeto, D., Yao, X., Forrest, G., and Marsh, D. J. (2012) Butyrate and propionate protect against dietinduced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS ONE 7, e35240.
96. 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., and Tsujimoto, G. (2013)The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43. Nat. Commun. 4, 1829.
97. Tolhurst, G., Heffron, H., Lam, Y. S., Parker, H. E., Habib, A. M., Diakogiannaki, E., Cameron, J., Grosse, J., Reimann, F., and Gribble, F.M. (2012) Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes 61, 364-371.
98. Galisteo, M., Duarte, J., and Zarzuelo, A. (2008) Effects of dietary fibers on disturbances clustered in themetabolic syndrome. J. Nutr. Biochem. 19, 71-84.
99. Alex, S., Lange, K., Amolo, T., Grinstead, J. S., Haakonsson, A. K., Szalowska, E., Koppen, A., Mudde, K., Haenen, D., Al-Lahham, S., Roelofsen, H., Houtman, R., van der Burg, B., Mandrup, S., Bonvin, A. M., Kalkhoven, E., Müller, M., Hooiveld, G. J., and Kersten, S. (2013) Short-chain fatty acids stimulate angiopoietin-like 4 synthesis in human colon adenocarcinoma cells by activating peroxisome proliferator-activated receptorg. Mol. Cell. Biol. 33, 1303-1316.
100. Den Besten, G., Bleeker, A., Gerding, A., van Eunen, K., Havinga, R., van Dijk, T. H., Oosterveer, M. H., Jonker, J. W., Groen, A. K., Reijngoud, D. J., and Bakker, B. M. (2015) Short-chain fatty acids protect against high-fat diet-induced obesity via a PPARg-dependent switch from lipogenesis to fat oxidation. [E-pub ahead of print]. Diabetes doi:10.2337/db14-1213.
101. Wang, Z., Klipfell, E., Bennett, B. J., Koeth, R., Levison, B. S., Dugar, B., Feldstein, A.E., Britt, E.B., Fu, X., Chung, Y. M., Wu, Y., Schauer, P., Smith, J. D., Allayee, H., Tang, W.H., DiDonato, J.A., Lusis, A. J., and Hazen, S.L. (2011)Gutflorametabolismofphosphatidylcholine promotes cardiovascular disease. Nature 472, 57-63.
102. 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., DiDonato, 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., and Hazen, S. L. (2013) Intestinal microbiota metabolism of L-carnitine, a nutrient in redmeat, promotes atherosclerosis. Nat.Med. 19, 576-585.
103. Koeth, R. A., Levison, B. S., Culley, M. K., Buffa, J. A., Wang, Z., Gregory, J. C., Org, E., Wu, Y., Li, L., Smith, J. D., Tang, W. H., DiDonato, J.A., Lusis, A. J., and Hazen, S.L. (2014)g-Butyrobetaine is a proatherogenic intermediate in gut microbialmetabolismof Lcarnitine to TMAO. Cell Metab. 20, 799-812.
104. Tang, W.H., Wang, Z., Levison, B. S., Koeth, R.A., Britt, E.B., Fu, X., Wu, Y., and Hazen, S. L. (2013) Intestinal microbial metabolismof phosphatidylcholine and cardiovascular risk. N. Engl. J. Med. 368, 1575-1584.
105. Hamer, H. M., De Preter, V., Windey, K., and Verbeke, K. (2012) Functional analysis of colonic bacterial metabolism: relevant to health? Am. J. Physiol. Gastrointest. Liver Physiol. 302, G1-G9.
106. Swann, J. R., Want, E. J., Geier, F. M., Spagou, K., Wilson, I. D., Sidaway, J. E., Nicholson, J. K., and Holmes, E. (2011) Systemic gut microbial modulation of bile acid metabolism in host tissue compartments. Proc. Natl. Acad. Sci. USA 108(Suppl 1), 4523-4530.
107. Vrieze, A., Out, C., Fuentes, S., Jonker, L., Reuling, I., Kootte, R. S., van Nood, E., Holleman, F., Knaapen, M., Romijn, J. A., Soeters, M. R., Blaak, E. E., Dallinga-Thie, G.M., Reijnders, D., Ackermans, M. T., Serlie, M. J., Knop, F. K., Holst, J. J., van der Ley, C., Kema, I. P., Zoetendal, E. G., de Vos, W. M., Hoekstra, J. B., Stroes, E. S., Groen, A.K., and Nieuwdorp, M. (2014) Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity. J. Hepatol. 60, 824-831.
108. Sayin, S. I., Wahlström, A., Felin, J., Jäntti, S., Marschall, H. U., Bamberg, K., Angelin, B., Hÿotyläinen, T., Orešič, M., and Bäckhed, F. (2013) Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metab. 17, 225-235.
109. Yokota, A., Fukiya, S., Islam, K. B., Ooka, T., Ogura, Y., Hayashi, T., Hagio, M., and Ishizuka, S. (2012) Is bile acid a determinant of the gut microbiota on a high-fat diet? Gut Microbes 3, 455-459.
110. Islam, K. B., Fukiya, S., Hagio, M., Fujii, N., Ishizuka, S., Ooka, T., Ogura, Y., Hayashi, T., and Yokota, A. (2011) Bile acid is ahost factor that regulates the composition of the cecal microbiota in rats. Gastroenterology 141, 1773-1781.
111. Devkota, S., Wang, Y., Musch, M.W., Leone, V., Fehlner-Peach, H., Nadimpalli, A., Antonopoulos, D. A., Jabri, B., and Chang, E. B. (2012) Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il102/2 mice. Nature 487, 104-108.
112. Binder, H. J., Filburn, B., and Floch, M. (1975) Bile acid inhibition of intestinal anaerobic organisms. Am. J. Clin. Nutr. 28, 119-125.
113. Yoshimoto, S., Loo, T. M., Atarashi, K., Kanda, H., Sato, S., Oyadomari, S., Iwakura, Y., Oshima, K., Morita, H., Hattori, M., Honda, K., Ishikawa, Y., Hara, E., and Ohtani, N. (2013) Obesityinduced gut microbial metabolite promotes liver cancer through senescence secretome. Nature 499, 97-101.
114. Fleissner, C. K., Huebel, N., Abd El-Bary, M. M., Loh, G., Klaus, S., and Blaut, M. (2010) Absence of intestinal microbiota does not protect mice from diet-induced obesity. Br. J. Nutr. 104, 919-929.
115. Swartz, T.D., Sakar, Y., Duca, F.A., and Covasa, M. (2013) Preserved adiposity in the Fischer 344 rat devoid of gut microbiota. FASEB J. 27, 1701-1710.
116. Robles Alonso, V., and Guarner, F. (2013) Linking the gut microbiota to human health. Br. J. Nutr. 109(Suppl 2), S21-S26.
117. Dewulf, E. M., Cani, P. D., Neyrinck, A. M., Possemiers, S., Van Holle, A., Muccioli, G. G., Deldicque, L., Bindels, L. B., Pachikian, B. D., Sohet, F. M., Mignolet, E., Francaux, M., Larondelle, Y., and Delzenne, N. M. (2011) Inulin-type fructans with prebiotic properties counteract GPR43 overexpression and PPARg-related adipogenesis in the white adipose tissue of high-fat diet-fed mice. J. Nutr. Biochem. 22, 712-722.
118. Arora, T., Singh, S., and Sharma, R. K. (2013) Probiotics: Interaction with gut microbiome and antiobesity potential. Nutrition 29, 591-596.
119. Panwar, H., Rashmi, H. M., Batish, V. K., and Grover, S. (2013) Probiotics as potential biotherapeutics in themanagement of type 2 diabetes: prospects and perspectives. Diabetes Metab. Res. Rev. 29, 103-112.
120. Million, M., Lagier, J. C., Yahav, D., and Paul, M. (2013) Gut bacterial microbiota and obesity. Clin. Microbiol. Infect. 19, 305-313.