The gut microbiota metabolite indole alleviates liver inflammation in mice

FASEB Journal

Volumn 32, Issue 12, 2018, Pages 6681-6693

  Beaumont, Martin ^b   Neyrinck, Audrey M ^b   Olivares, Marta ^b   Rodriguez, Julie ^b   De Rocca Serra, Audrey ^a   Roumain, Martin ^b   Bindels, Laure B ^b   Cani, Patrice D ^b   Evenepoel, Pieter ^c   Muccioli, Giulio G ^b   Demoulin, Jean Baptiste ^a   Delzenne, Nathalie M ^b  

^a DE DUVE INSTITUTE   (Belgium)

^b UNIVERSITÉ CATHOLIQUE DE LOUVAIN   (Belgium)

^c UNIVERSITY OF LEUVEN   (Belgium)

Author keywords

Cholesterol metabolism; Gut liver axis; Kupffer cells; LPS; PCLS

Indexed keywords

4BETA HYDROXYCHOLESTEROL; AROMATIC AMINO ACID; BENZOIC ACID; CHOLESTEROL DERIVATIVE; CRYOPYRIN; ENDOTOXIN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INDOLE; MESSENGER RNA; PARA CRESOL; PHENYLACETIC ACID; TRANSCRIPTOME; TRYPTOPHAN; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIINFLAMMATORY ACTIVITY; ARTICLE; CHOLESTEROL LIVER LEVEL; CHOLESTEROL METABOLISM; CONTROLLED STUDY; DOWN REGULATION; DRUG MECHANISM; GENE EXPRESSION; HEPATITIS; IN VITRO STUDY; IN VIVO STUDY; INTESTINE FLORA; KUPFFER CELL; LIPOPOLYSACCHARIDE-INDUCED INFLAMMATION; LIVER SLICE; MALE; MOUSE; NONHUMAN; OB/OB MOUSE; PRIORITY JOURNAL; TRANSCRIPTION REGULATION; UPREGULATION; XENOBIOTIC METABOLISM;

EID: 85055470325     PISSN: 08926638     EISSN: 15306860     Source Type: Journal    
DOI: 10.1096/fj.201800544     Document Type: Article

References (59)

1. Strnad, P., Tacke, F., Koch, A., and Trautwein, C. (2017) Liver—guardian, modifier and target of sepsis. Nat. Rev. Gastroenterol. Hepatol. 14, 55–66
2. Cani, P. D., Bibiloni, R., Knauf, C., Waget, A., Neyrinck, A. M., Delzenne, N. M., and Burcelin, R. (2008) Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet–induced obesity and diabetes in mice. Diabetes 57, 1470–1481
3. Cani, P. D., Possemiers, S., Van de Wiele, T., Guiot, Y., Everard, A., Rottier, O., Geurts, L., Naslain, D., Neyrinck, A., Lambert, D. M., Muccioli, G. G., and Delzenne, N. M. (2009) Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2–driven improvement of gut permeability. Gut 58, 1091–1103
4. Brandl, K., Kumar, V., and Eckmann, L. (2017) Gut–liver axis at the frontier of host–microbial interactions. Am. J. Physiol. Gastrointest. Liver Physiol. 312, G413–G419
5. Heymann, F., and Tacke, F. (2016) Immunology in the liver—from homeostasis to disease. Nat. Rev. Gastroenterol. Hepatol. 13, 88–110
6. Luedde, T., and Schwabe, R. F. (2011) NF-kB in the liver—linking injury, fibrosis and hepatocellular carcinoma. Nat. Rev. Gastroenterol. Hepatol. 8, 108–118
7. Chassaing, B., Etienne-Mesmin, L., and Gewirtz, A. T. (2014) Microbiota–liver axis in hepatic disease. Hepatology 59, 328–339
8. Szabo, G., and Petrasek, J. (2015) Inflammasome activation and function in liver disease. Nat. Rev. Gastroenterol. Hepatol. 12, 387–400
9. Tilg, H., Cani, P. D., and Mayer, E. A. (2016) Gut microbiome and liver diseases. Gut 65, 2035–2044
10. Llopis, M., Cassard, A. M., Wrzosek, L., Boschat, L., Bruneau, A., Ferrere, G., Puchois, V., Martin, J. C., Lepage, P., Le Roy, T., Lefèvre, L., Langelier, B., Cailleux, F., González-Castro, A. M., Rabot, S., Gaudin, F., Agostini, H., Prévot, S., Berrebi, D., Ciocan, D., Jousse, C., Naveau, S., Gérard, P., and Perlemuter, G. (2016) Intestinal microbiota contributes to individual susceptibility to alcoholic liver disease. Gut 65, 830–839
11. 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., and Diehl, A. M. (2016) The severity of nonalcoholic fatty liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota. Hepatology 63, 764–775
12. Leung, C., Rivera, L., Furness, J. B., and Angus, P. W. (2016) The role of the gut microbiota in NAFLD. Nat. Rev. Gastroenterol. Hepatol. 13, 412–425
13. Blander, J. M., Longman, R. S., Iliev, I. D., Sonnenberg, G. F., and Artis, D. (2017) Regulation of inflammation by microbiota interactions with the host. Nat. Immunol. 18, 851–860
14. Schnabl, B., and Brenner, D. A. (2014) Interactions between the intestinalmicrobiomeandliverdiseases.Gastroenterology146,1513–1524
15. Wikoff, W. R., Anfora, A. T., Liu, J., Schultz, P. G., Lesley, S. A., Peters, E. C., and Siuzdak, G. (2009) Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc. Natl. Acad. Sci. USA 106, 3698–3703
16. Zheng, X., Xie, G., Zhao, A., Zhao, L., Yao, C., Chiu, N. H. L., Zhou, Z., Bao, Y., Jia, W., Nicholson, J. K., and Jia, W. (2011) The footprints of gut microbial–mammalian co-metabolism. J. Proteome Res. 10, 5512–5522
17. Portune, K. J., Beaumont, M., Davila, A.-M., Tomé, D., Blachier, F., and Sanz, Y. (2016) Gut microbiota role in dietary protein metabolism and health-related outcomes: the two sides of the coin. Trends Food Sci. Technol. 57, 213–232
18. De Graaf, I. A. M., Olinga, P., de Jager, M. H., Merema, M. T., de Kanter, R., van de Kerkhof, E. G., and Groothuis, G. M. M. (2010) Preparation and incubation of precision-cut liver and intestinal slices for application in drug metabolism and toxicity studies. Nat. Protoc. 5, 1540–1551
19. Whitfield-Cargile, C. M., Cohen, N. D., Chapkin, R. S., Weeks, B. R., Davidson, L. A., Goldsby, J. S., Hunt, C. L., Steinmeyer, S. H., Menon, R., Suchodolski, J. S., Jayaraman, A., and Alaniz, R. C. (2016) The microbiota-derived metabolite indole decreases mucosal inflammation and injury in a murine model of NSAID enteropathy. Gut Microbes 7, 246–261
20. Li, P. Z., Li, J. Z., Li, M., Gong, J. P., and He, K. (2014) An efficient method to isolate and culture mouse Kupffer cells. Immunol. Lett. 158, 52–56
21. Neyrinck, A. M., Possemiers, S., Verstraete, W., De Backer, F., Cani, P. D., and Delzenne, N. M. (2012) Dietary modulation of clostridial cluster XIVa gut bacteria (Roseburia spp.) by chitin–glucan fiber improves host metabolic alterations induced by high-fat diet in mice. J. Nutr. Biochem. 23, 51–59
22. Mutemberezi, V., Masquelier, J., Guillemot-Legris, O., and Muccioli, G. G. (2016) Development and validation of an HPLC-MS method for the simultaneous quantification of key oxysterols, endocannabinoids, and ceramides: variations in metabolic syndrome. Anal. Bioanal. Chem. 408, 733–745
23. Neyrinck, A. M., Etxeberria, U., Taminiau, B., Daube, G., Van Hul, M., Everard, A., Cani, P. D., Bindels, L. B., and Delzenne, N. M. (In press) Rhubarb extract prevents hepatic inflammation induced by acute alcohol intake, an effect related to the modulation of the gut microbiota. Mol. Nutr. Food Res. 61
24. Andriamihaja, M., Lan, A., Beaumont, M., Audebert, M., Wong, X., Yamada, K., Yin, Y., Tomé, D., Carrasco-Pozo, C., Gotteland, M., Kong, X., and Blachier, F. (2015) The deleterious metabolic and genotoxic effects of the bacterial metabolite p-cresol on colonic epithelial cells. Free Radic. Biol. Med. 85, 219–227
25. Bansal, T., Alaniz, R. C., Wood, T. K., and Jayaraman, A. (2010) The bacterial signal indole increases epithelial-cell tight-junction resistance and attenuates indicators of inflammation. Proc. Natl. Acad. Sci. USA 107, 228–233
26. Shimada, Y., Kinoshita, M., Harada, K., Mizutani, M., Masahata, K., Kayama, H., and Takeda, K. (2013) Commensal bacteria–dependent indole production enhances epithelial barrier function in the colon. PLoS One 8, e80604
27. Tacke, F. (2017) Targeting hepatic macrophages to treat liver diseases. J. Hepatol. 66, 1300–1312
28. Van Rooijen, N., and Sanders, A. (1996) Kupffer cell depletion by liposome-delivered drugs: comparative activity of intracellular clodronate, propamidine, and ethylenediaminetetraacetic acid. Hepatology 23, 1239–1243
29. Banoglu, E., Jha, G. G., and King, R. S. (2001) Hepatic microsomal metabolism of indole to indoxyl, a precursor of indoxyl sulfate. Eur. J. Drug Metab. Pharmacokinet. 26, 235–240
30. Banoglu, E., and King, R. S. (2002) Sulfation of indoxyl by human and rat aryl (phenol) sulfotransferases to form indoxyl sulfate. Eur. J. Drug Metab. Pharmacokinet. 27, 135–140
31. Murray, I. A., Patterson, A. D., and Perdew, G. H. (2014) Aryl hydrocarbon receptor ligands in cancer: friend and foe. Nat. Rev. Cancer 14, 801–814
32. Schulman, I. G. (2017) Liver X receptors link lipid metabolism and inflammation. FEBS Lett. 591, 2978–2991
33. Lee, J.-H., and Lee, J. (2010) Indole as an intercellular signal in microbial communities. FEMS Microbiol. Rev. 34, 426–444
34. Jin, U.-H., Lee, S.-O., Sridharan, G., Lee, K., Davidson, L. A., Jayaraman, A., Chapkin, R. S., Alaniz, R., and Safe, S. (2014) Microbiome-derived tryptophan metabolites and their aryl hydrocarbon receptor-dependent agonist and antagonist activities. Mol. Pharmacol. 85, 777–788
35. Zelante, T., Iannitti, R. G., Cunha, C., De Luca, A., Giovannini, G., Pieraccini, G., Zecchi, R., D’Angelo, C., Massi-Benedetti, C., Fallarino, F., Carvalho, A., Puccetti, P., and Romani, L. (2013) Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity 39, 372–385
36. Venkatesh, M., Mukherjee, S., Wang, H., Li, H., Sun, K., Benechet, A. P., Qiu, Z., Maher, L., Redinbo, M. R., Phillips, R. S., Fleet, J. C., Kortagere, S., Mukherjee, P., Fasano, A., Le Ven, J., Nicholson, J. K., Dumas, M. E., Khanna, K. M., and Mani, S. (2014) Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4. Immunity 41, 296–310
37. Jennis, M., Cavanaugh, C. R., Leo, G. C., Mabus, J. R., Lenhard, J., and Hornby, P. J. (In press) Microbiota-derived tryptophan indoles increase after gastric bypass surgery and reduce intestinal permeability in vitro and in vivo. Neurogastroenterol. Motil. 30
38. + T cells. Science 357, 806–810
39. Piñero-Fernandez, S., Chimerel, C., Keyser, U. F., and Summers, D. K. (2011) Indole transport across Escherichia coli membranes. J. Bacteriol. 193, 1793–1798
40. Kitchens, R. L., and Thompson, P. A. (2005) Modulatory effects of sCD14 and LBP on LPS–host cell interactions. J. Endotoxin Res. 11, 225–229
41. Petrasek, J., Bala, S., Csak, T., Lippai, D., Kodys, K., Menashy, V., Barrieau, M., Min, S.-Y., Kurt-Jones, E. A., and Szabo, G. (2012) IL-1 receptor antagonist ameliorates inflammasome-dependent alcoholic steatohepatitis in mice. J. Clin. Invest. 122, 3476–3489
42. Quiroga, J., and Prieto, J. (1993) Liver cytoprotection by prostaglandins. Pharmacol. Ther. 58, 67–91
43. Neyrinck, A. M., Alexiou, H., and Delzenne, N. M. (2004) Kupffer cell activity is involved in the hepatoprotective effect of dietary oligofructose in rats with endotoxic shock. J. Nutr. 134, 1124–1129
44. Neyrinck, A. M., Gomez, C., and Delzenne, N. M. (2004) Precision-cut liver slices in culture as a tool to assess the physiological involvement of Kupffer cells in hepatic metabolism. Comp. Hepatol. 3(Suppl 1), S45
45. Rasmussen, M. K., Balaguer, P., Ekstrand, B., Daujat-Chavanieu, M., and Gerbal-Chaloin, S. (2016) Skatole (3-methylindole) is a partial aryl hydrocarbon receptor agonist and induces CYP1A1/2 and CYP1B1 expression in primary human hepatocytes. PLoS One 11, e0154629
46. Cheng, Y., Jin, U.-H., Allred, C. D., Jayaraman, A., Chapkin, R. S., and Safe, S. (2015) Aryl hydrocarbon receptor activity of tryptophan metabolites in young adult mouse colonocytes. Drug Metab. Dispos. 43, 1536–1543
47. Hubbard, T. D., Murray, I. A., Bisson, W. H., Lahoti, T. S., Gowda, K., Amin, S. G., Patterson, A. D., and Perdew, G. H. (2015) Adaptation of the human aryl hydrocarbon receptor to sense microbiota-derived indoles. Sci. Rep. 5, 12689
48. Xu, J., Kulkarni, S. R., Li, L., and Slitt, A. L. (2012) UDP-glucuronosyltransferase expression in mouse liver is increased in obesity- and fasting-induced steatosis. Drug Metab. Dispos. 40, 259–266
49. Schroeder, J. C., Dinatale, B. C., Murray, I. A., Flaveny, C. A., Liu, Q., Laurenzana, E. M., Lin, J. M., Strom, S. C., Omiecinski, C. J., Amin, S., and Perdew, G. H. (2010) The uremic toxin 3-indoxyl sulfate is a potent endogenous agonist for the human aryl hydrocarbon receptor. Biochemistry 49, 393–400
50. Tall, A. R., and Yvan-Charvet, L. (2015) Cholesterol, inflammation and innate immunity. Nat. Rev. Immunol. 15, 104–116
51. Feingold, K. R., and Grunfeld, C. (2010) The acute phase response inhibits reverse cholesterol transport. J. Lipid Res. 51, 682–684
52. Mutemberezi, V., Guillemot-Legris, O., and Muccioli, G. G. (2016) Oxysterols: from cholesterol metabolites to key mediators. Prog. Lipid Res. 64, 152–169
53. Ritze, Y., Bárdos, G., Hubert, A., Böhle, M., and Bischoff, S. C. (2014) Effect of tryptophan supplementation on diet-induced non-alcoholic fatty liver disease in mice. Br. J. Nutr. 112, 1–7
54. Osawa, Y., Kanamori, H., Seki, E., Hoshi, M., Ohtaki, H., Yasuda, Y., Ito, H., Suetsugu, A., Nagaki, M., Moriwaki, H., Saito, K., and Seishima, M. (2011) L-Tryptophan–mediated enhancement of susceptibility to nonalcoholic fatty liver disease is dependent on the mammalian target of rapamycin. J. Biol. Chem. 286, 34800–34808
55. Rothhammer, V., Mascanfroni, I. D., Bunse, L., Takenaka, M. C., Kenison, J. E., Mayo, L., Chao, C.-C., Patel, B., Yan, R., Blain, M., Alvarez, J. I., Kébir, H., Anandasabapathy, N., Izquierdo, G., Jung, S., Obholzer, N., Pochet, N., Clish, C. B., Prinz, M., Prat, A., Antel, J., and Quintana, F. J. (2016) Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor. Nat. Med. 22, 586–597
56. Sonowal, R., Swimm, A., Sahoo, A., Luo, L., Matsunaga, Y., Wu, Z., Bhingarde, J. A., Ejzak, E. A., Ranawade, A., Qadota, H., Powell, D. N., Capaldo, C. T., Flacker, J. M., Jones, R. M., Benian, G. M., and Kalman, D. (2017) Indoles from commensal bacteria extend healthspan. Proc. Natl. Acad. Sci. USA 114, E7506–E7515
57. Gaudichon, C., Bos, C., Morens, C., Petzke, K. J., Mariotti, F., Everwand, J., Benamouzig, R., Daré, S., Tomé, D., and Metges, C. C. (2002) Ileal losses of nitrogen and amino acids in humans and their importance to the assessment of amino acid requirements. Gastroenterology 123, 50–59
58. Beaumont, M., Portune, K. J., Steuer, N., Lan, A., Cerrudo, V., Audebert, M., Dumont, F., Mancano, G., Khodorova, N., Andriamihaja, M., Airinei, G., Tomé, D., Benamouzig, R., Davila, A.-M., Claus, S. P., Sanz, Y., and Blachier, F. (2017) Quantity and source of dietary protein influence metabolite production by gut microbiota and rectal mucosa gene expression: a randomized, parallel, double-blind trial in overweight humans. Am. J. Clin. Nutr. 106, 1005–1019
59. Klemashevich, C., Wu, C., Howsmon, D., Alaniz, R. C., Lee, K., and Jayaraman, A. (2014) Rational identification of diet-derived post-biotics for improving intestinal microbiota function. Curr. Opin. Bio-technol. 26, 85–90