Microbiome-modulated metabolites at the interface of host immunity

Journal of Immunology

Volumn 198, Issue 2, 2017, Pages 572-580

  Blacher, Eran ^a   Levy, Maayan ^a   Tatirovsky, Evgeny ^a   Elinav, Eran ^a  

^a WEIZMANN INSTITUTE OF SCIENCE   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

BIOSYNTHESIS; CELL FUNCTION; CELL MATURATION; DIGESTION; DISEASE ASSOCIATION; EPIGENETICS; FERMENTATION; GENETIC TRANSCRIPTION; IMMUNITY; IMMUNOMODULATION; IMMUNOREGULATION; INTESTINE FLORA; METABOLITE; MICROBIOME; MOLECULAR MECHANICS; NONALCOHOLIC FATTY LIVER; NONHUMAN; NUCLEAR REPROGRAMMING; REVIEW; SECONDARY METABOLISM; ANIMAL; HUMAN; IMMUNE SYSTEM; IMMUNOLOGY; MUCOSAL IMMUNITY; SIGNAL TRANSDUCTION;

ANIMALS; GASTROINTESTINAL MICROBIOME; HUMANS; IMMUNE SYSTEM; IMMUNITY, MUCOSAL; RECEPTOR CROSS-TALK;

EID: 85014707675     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1601247     Document Type: Review

References (99)

1. Veldhoen, M., and V. Brucklacher-Waldert. 2012. Dietary influences on intestinal immunity. Nat. Rev. Immunol. 12: 696-708
2. Lee, W.-J., and K. Hase. 2014. Gut microbiota-generated metabolites in animal health and disease. Nat. Chem. Biol. 10: 416-424
3. Zheng, X., G. Xie, A. Zhao, L. Zhao, C. Yao, N. H. L. Chiu, Z. Zhou, Y. Bao, W. Jia, J. K. Nicholson, and W. Jia. 2011. The footprints of gut microbialmammalian co-metabolism. J. Proteome Res. 10: 5512-5522
4. Gargaro, M., M. Pirro, R. Romani, T. Zelante, and F. Fallarino. 2016. AhRdependent pathways in immune regulation. Am. J. Transplant. 16: 2270-2276
5. Gaudet, R. G., A. Sintsova, C. M. Buckwalter, N. Leung, A. Cochrane, J. Li, A. D. Cox, J. Moffat, and S. D. Gray-Owen. 2015. Cytosolic detection of the bacterial metabolite HBP activates TIFA-dependent innate immunity. Science 348: 1251-1255
6. Hall, J. A., J. L. Cannons, J. R. Grainger, L. M. Dos Santos, T. W. Hand, S. Naik, E. A. Wohlfert, D. B. Chou, G. Oldenhove, M. Robinson, et al. 2011. Essential role for retinoic acid in the promotion of CD4(+) T cell effector responses via retinoic acid receptor alpha. Immunity 34: 435-447
7. Lamas, B., M. L. Richard, V. Leducq, H.-P. Pham, M.-L. Michel, G. Da Costa, C. Bridonneau, S. Jegou, T. W. Hoffmann, J. M. Natividad, et al. 2016. CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. Nat. Med. 22: 598-605
8. Mader, D., M. J. Rabiet, F. Boulay, and A. Peschel. 2010. Formyl peptide receptormediated proinflammatory consequences of peptide deformylase inhibition in Staphylococcus aureus. Microbes Infect. 12: 415-419
9. Thorburn, A. N., L. Macia, and C. R. Mackay. 2014. Diet, metabolites, and "western-lifestyle" inflammatory diseases. Immunity 40: 833-842
10. Tan, J., C. McKenzie, M. Potamitis, A. N. Thorburn, C. R. Mackay, and L. Macia. 2014. The role of short-chain fatty acids in health and disease. Adv. Immunol. 121: 91-119
11. Rothhammer, V., I. D. Mascanfroni, L. Bunse, M. C. Takenaka, J. E. Kenison, L. Mayo, C.-C. Chao, B. Patel, R. Yan, M. Blain, et al. 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
12. Butovsky, O., A. E. Talpalar, K. Ben-Yaakov, and M. Schwartz. 2005. Activation of microglia by aggregated b-amyloid or lipopolysaccharide impairs MHC-II expression and renders them cytotoxic whereas IFN-g and IL-4 render them protective. Mol. Cell. Neurosci. 29: 381-393
13. Koren, O., J. K. Goodrich, T. C. Cullender, A. Spor, K. Laitinen, H. K. Bäckhed, A. Gonzalez, J. J. Werner, L. T. Angenent, R. Knight, et al. 2012. Host remodeling of the gut microbiome and metabolic changes during pregnancy. Cell 150: 470-480
14. Ley, R. E., D. A. Peterson, and J. I. Gordon. 2006. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 124: 837-848
15. Martin, F. P. J., N. Sprenger, I. Montoliu, S. Rezzi, S. Kochhar, and J. K. Nicholson. 2010. Dietary modulation of gut functional ecology studied by fecal metabonomics. J. Proteome Res. 9: 5284-5295
16. Marcobal, A., T. Yusufaly, S. Higginbottom, M. Snyder, J. L. Sonnenburg, and G. I. Mias. 2015. Metabolome progression during early gut microbial colonization of gnotobiotic mice. Sci. Rep. 5: 11589
17. Matsumoto, M., R. Kibe, T. Ooga, Y. Aiba, S. Kurihara, E. Sawaki, Y. Koga, and Y. Benno. 2012. Impact of intestinal microbiota on intestinal luminal metabolome. Sci. Rep. 2: 233
18. Nicholls, A. W., R. J. Mortishire-Smith, and J. K. Nicholson. 2003. NMR spectroscopic-based metabonomic studies of urinary metabolite variation in acclimatizing germ-free rats. Chem. Res. Toxicol. 16: 1395-1404
19. Pryde, S. E., S. H. Duncan, G. L. Hold, C. S. Stewart, and H. J. Flint. 2002. The microbiology of butyrate formation in the human colon. FEMS Microbiol. Lett. 217: 133-139
20. Topping, D. L., and P. M. Clifton. 2001. Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiol. Rev. 81: 1031-1064
21. Card, D. J., R. Gorska, J. Cutler, and D. J. Harrington. 2014. Vitamin K metabolism: current knowledge and future research. Mol. Nutr. Food Res. 58: 1590-1600
22. Xu, Z., Q. Qiu, J. Tian, J. S. Smith, G. M. Conenello, T. Morita, and A. P. Byrnes. 2013. Coagulation factor X shields adenovirus type 5 from attack by natural antibodies and complement. Nat. Med. 19: 452-457
23. Biesalski, H. K. 2016. Nutrition meets the microbiome: micronutrients and the microbiota. Ann. N. Y. Acad. Sci. 1372: 53-64
24. Beulens, J. W. J., S. L. Booth, E. G. H. M. van den Heuvel, E. Stoecklin, A. Baka, and C. Vermeer. 2013. The role of menaquinones (Vitamin K2) in human health. Br. J. Nutr. 110: 1357-1368
25. Conly, J., and K. Stein. 1994. Reduction of Vitamin K2 concentrations in human liver associated with the use of broad spectrum antimicrobials. Clin. Invest. Med. 17: 531-539
26. Komai, M., H. Shirakawa, and S. Kimura. 1988. Newly developed model for Vitamin K deficiency in germfree mice. Int. J. Vitam. Nutr. Res. 58: 55-59
27. Davidson, R. T., A. L. Foley, J. A. Engelke, and J. W. Suttie. 1998. Conversion of dietary phylloquinone to tissue menaquinone-4 in rats is not dependent on gut bacteria. J. Nutr. 128: 220-223
28. Champagne, C. P., T. A. Tompkins, N. D. Buckley, and J. M. Green-Johnson. 2010. Effect of fermentation by pure and mixed cultures of Streptococcus thermophilus and Lactobacillus helveticus on isoflavone and B-Vitamin content of a fermented soy beverage. Food Microbiol. 27: 968-972
29. Pompei, A., L. Cordisco, A. Amaretti, S. Zanoni, D. Matteuzzi, and M. Rossi. 2007. Folate production by bifidobacteria as a potential probiotic property. Appl. Environ. Microbiol. 73: 179-185
30. Degnan, P. H., M. E. Taga, and A. L. Goodman. 2014. Vitamin B12 as a modulator of gut microbial ecology. Cell Metab. 20: 769-778
31. Zelante, T., R. G. Iannitti, C. Cunha, A. De Luca, G. Giovannini, G. Pieraccini, R. Zecchi, C. D'Angelo, C. Massi-Benedetti, F. Fallarino, et al. 2013. Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity 39: 372-385
32. Hashimoto, T., T. Perlot, A. Rehman, J. Trichereau, H. Ishiguro, M. Paolino, V. Sigl, T. Hanada, R. Hanada, S. Lipinski, et al. 2012. ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. Nature 487: 477-481
33. de Aguiar Vallim, T. Q., E. J. Tarling, and P. A. Edwards. 2013. Pleiotropic roles of bile acids in metabolism. Cell Metab. 17: 657-669
34. Wahlström, A., S. I. Sayin, H.-U. Marschall, and F. Bäckhed. 2016. Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism. Cell Metab. 24: 41-50
35. Ridlon, J. M., D.-J. Kang, and P. B. Hylemon. 2006. Bile salt biotransformations by human intestinal bacteria. J. Lipid Res. 47: 241-259
36. Swann, J. R., E. J. Want, F. M. Geier, K. Spagou, I. D. Wilson, J. E. Sidaway, J. K. Nicholson, and E. Holmes. 2011. Systemic gut microbial modulation of bile acid metabolism in host tissue compartments. Proc. Natl. Acad. Sci. USA 108(Suppl. 1): 4523-4530
37. Wang, H., J. Chen, K. Hollister, L. C. Sowers, and B. M. Forman. 1999. Endogenous bile acids are ligands for the nuclear receptor FXR/BAR. Mol. Cell 3: 543-553
38. Inagaki, T., A. Moschetta, Y.-K. Lee, L. Peng, G. Zhao, M. Downes, R. T. Yu, J. M. Shelton, J. A. Richardson, J. J. Repa, et al. 2006. Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor. Proc. Natl. Acad. Sci. USA 103: 3920-3925
39. Pols, T. W. H., M. Nomura, T. Harach, G. Lo Sasso, M. H. Oosterveer, C. Thomas, G. Rizzo, A. Gioiello, L. Adorini, R. Pellicciari, et al. 2011. TGR5 activation inhibits atherosclerosis by reducing macrophage inflammation and lipid loading. Cell Metab. 14: 747-757
40. Vavassori, P., A. Mencarelli, B. Renga, E. Distrutti, and S. Fiorucci. 2009. The bile acid receptor FXR is a modulator of intestinal innate immunity. J. Immunol. 183: 6251-6261
41. Ridaura, V. K., J. J. Faith, F. E. Rey, J. Cheng, A. E. Duncan, A. L. Kau, N. W. Griffin, V. Lombard, B. Henrissat, J. R. Bain, et al. 2013. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 341: 1241214
42. Yoshimoto, S., T. M. Loo, K. Atarashi, H. Kanda, S. Sato, S. Oyadomari, Y. Iwakura, K. Oshima, H. Morita, M. Hattori, et al. 2013. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature 499: 97-101
43. Levy, M., C. A. Thaiss, D. Zeevi, L. Dohnalová, G. Zilberman-Schapira, J. A. Mahdi, E. David, A. Savidor, T. Korem, Y. Herzig, et al. 2015. Microbiotamodulated metabolites shape the intestinal microenvironment by regulating NLRP6 inflammasome signaling. Cell 163: 1428-1443
44. Donohoe, D. R., A. Wali, B. P. Brylawski, and S. J. Bultman. 2012. Microbial regulation of glucose metabolism and cell-cycle progression in mammalian colonocytes. PLoS One 7: e46589
45. Donohoe, D. R., N. Garge, X. Zhang, W. Sun, T. M. O'Connell, M. K. Bunger, and S. J. Bultman. 2011. The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. Cell Metab. 13: 517-526
46. Sanderson, I. R. 2004. Short chain fatty acid regulation of signaling genes expressed by the intestinal epithelium. J. Nutr. 134: 2450S-2454S
47. Buck, M. D., D. O'Sullivan, and E. L. Pearce. 2015. T cell metabolism drives immunity. J. Exp. Med. 212: 1345-1360
48. Chung, H., S. J. Pamp, J. A. Hill, N. K. Surana, S. M. Edelman, E. B. Troy, N. C. Reading, E. J. Villablanca, S. Wang, J. R. Mora, et al. 2012. Gut immune maturation depends on colonization with a host-specific microbiota. Cell 149: 1578-1593
49. Gaudier, E., A. Jarry, H. M. Blottière, P. de Coppet, M. P. Buisine, J. P. Aubert, C. Laboisse, C. Cherbut, and C. Hoebler. 2004. Butyrate specifically modulates MUC gene expression in intestinal epithelial goblet cells deprived of glucose. Am. J. Physiol. Gastrointest. Liver Physiol. 287: G1168-G1174
50. Willemsen, L. E. M., M. A. Koetsier, S. J. van Deventer, and E. A. van Tol. 2003. Short chain fatty acids stimulate epithelial mucin 2 expression through differential effects on prostaglandin E(1) and E(2) production by intestinal myofibroblasts. Gut 52: 1442-1447
51. Wrzosek, L., S. Miquel, M.-L. Noordine, S. Bouet, M. Joncquel Chevalier-Curt, V. Robert, C. Philippe, C. Bridonneau, C. Cherbuy, C. Robbe-Masselot, et al. 2013. Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii influence the production of mucus glycans and the development of goblet cells in the colonic epithelium of a gnotobiotic model rodent. BMC Biol. 11: 61
52. Arpaia, N., C. Campbell, X. Fan, S. Dikiy, J. van der Veeken, P. deRoos, H. Liu, J. R. Cross, K. Pfeffer, P. J. Coffer, and A. Y. Rudensky. 2013. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 504: 451-455
53. Chang, P. V., L. Hao, S. Offermanns, and R. Medzhitov. 2014. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc. Natl. Acad. Sci. USA 111: 2247-2252
54. Smith, P. M., M. R. Howitt, N. Panikov, M. Michaud, C. A. Gallini, M. Bohlooly-Y, J. N. Glickman, and W. S. Garrett. 2013. The microbial metabolites, short-chain fatty acids, regulate colonic treg cell homeostasis. Science 341: 569-573
55. Furusawa, Y., Y. Obata, S. Fukuda, T. A. Endo, G. Nakato, D. Takahashi, Y. Nakanishi, C. Uetake, K. Kato, T. Kato, et al. 2013. Commensal microbederived butyrate induces the differentiation of colonic regulatory T cells. Nature 504: 446-450
56. Singh, N., A. Gurav, S. Sivaprakasam, E. Brady, R. Padia, H. Shi, M. Thangaraju, P. D. Prasad, S. Manicassamy, D. H. Munn, et al. 2014. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity 40: 128-139
57. Thorburn, A. N., C. I. McKenzie, S. Shen, D. Stanley, L. Macia, L. J. Mason, L. K. Roberts, C. H. Y. Wong, R. Shim, R. Robert, et al. 2015. Evidence that asthma is a developmental origin disease influenced by maternal diet and bacterial metabolites. Nat. Commun. 6: 7320
58. Vinolo, M. A. R., H. G. Rodrigues, E. Hatanaka, F. T. Sato, S. C. Sampaio, and R. Curi. 2011. Suppressive effect of short-chain fatty acids on production of proinflammatory mediators by neutrophils. J. Nutr. Biochem. 22: 849-855
59. Usami, M., K. Kishimoto, A. Ohata, M. Miyoshi, M. Aoyama, Y. Fueda, and J. Kotani. 2008. Butyrate and trichostatin A attenuate nuclear factor kappaB activation and tumor necrosis factor alpha secretion and increase prostaglandin E2 secretion in human peripheral blood mononuclear cells. Nutr. Res. 28: 321-328
60. Trompette, A., E. S. Gollwitzer, K. Yadava, A. K. Sichelstiel, N. Sprenger, C. Ngom-Bru, C. Blanchard, T. Junt, L. P. Nicod, N. L. Harris, and B. J. Marsland. 2014. Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat. Med. 20: 159-166
61. Singh, N., M. Thangaraju, P. D. Prasad, P. M. Martin, N. A. Lambert, T. Boettger, S. Offermanns, and V. Ganapathy. 2010. Blockade of dendritic cell development by bacterial fermentation products butyrate and propionate through a transporter (Slc5a8)-dependent inhibition of histone deacetylases. J. Biol. Chem. 285: 27601-27608
62. Macia, L., J. Tan, A. T. Vieira, K. Leach, D. Stanley, S. Luong, M. Maruya, C. Ian McKenzie, A. Hijikata, C. Wong, et al. 2015. Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome. Nat. Commun. 6: 6734
63. Fukuda, S., H. Toh, K. Hase, K. Oshima, Y. Nakanishi, K. Yoshimura, T. Tobe, J. M. Clarke, D. L. Topping, T. Suzuki, et al. 2011. Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature 469: 543-547
64. Gury-BenAri, M., C. A. Thaiss, N. Serafini, D. R. Winter, A. Giladi, D. Lara-Astiaso, M. Levy, T. M. Salame, A. Weiner, E. David, et al. 2016. The spectrum and regulatory landscape of intestinal innate lymphoid cells are shaped by the microbiome. Cell 166: 1231-1246.e13
65. Ivanov, I. I., K. Atarashi, N. Manel, E. L. Brodie, T. Shima, U. Karaoz, D. Wei, K. C. Goldfarb, C. A. Santee, S. V. Lynch, et al. 2009. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139: 485-498
66. Goto, Y., C. Panea, G. Nakato, A. Cebula, C. Lee, M. G. Diez, T. M. Laufer, L. Ignatowicz, and I. I. Ivanov. 2014. Segmented filamentous bacteria antigens presented by intestinal dendritic cells drive mucosal Th17 cell differentiation. Immunity 40: 594-607
67. Maslowski, K. M., A. T. Vieira, A. Ng, J. Kranich, F. Sierro, D. Yu, H. C. Schilter, M. S. Rolph, F. Mackay, D. Artis, et al. 2009. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 461: 1282-1286
68. Giongo, A., K. A. Gano, D. B. Crabb, N. Mukherjee, L. L. Novelo, G. Casella, J. C. Drew, J. Ilonen, M. Knip, H. Hyöty, et al. 2011. Toward defining the autoimmune microbiome for type 1 diabetes. ISME J. 5: 82-91
69. Henao-Mejia, J., E. Elinav, C. A. Thaiss, P. Licona-Limon, and R. A. Flavell. 2013. Role of the intestinal microbiome in liver disease. J. Autoimmun. 46: 66-73
70. Kostic, A. D., R. J. Xavier, and D. Gevers. 2014. The microbiome in inflammatory bowel disease: current status and the future ahead. Gastroenterology 146: 1489-1499
71. Sears, C. L., and W. S. Garrett. 2014. Microbes, microbiota, and colon cancer. Cell Host Microbe 15: 317-328
72. Parracho, H. M. R. T., M. O. Bingham, G. R. Gibson, and A. L. McCartney. 2005. Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. J. Med. Microbiol. 54: 987-991
73. Tang, W. H. W., and S. L. Hazen. 2014. The contributory role of gut microbiota in cardiovascular disease. J. Clin. Invest. 124: 4204-4211
74. Qiu, J., X. Guo, Z.-M. E. Chen, L. He, G. F. Sonnenberg, D. Artis, Y.-X. Fu, and L. Zhou. 2013. Group 3 innate lymphoid cells inhibit T-cell-mediated intestinal inflammation through aryl hydrocarbon receptor signaling and regulation of microflora. Immunity 39: 386-399
75. Li, Y., S. Innocentin, D. R. Withers, N. A. Roberts, A. R. Gallagher, E. F. Grigorieva, C. Wilhelm, and M. Veldhoen. 2011. Exogenous stimuli maintain intraepithelial lymphocytes via aryl hydrocarbon receptor activation. Cell 147: 629-640
76. Park, J., M. Kim, S. G. Kang, A. H. Jannasch, B. Cooper, J. Patterson, and C. H. Kim. 2015. Short-chain fatty acids induce both effector and regulatory T cells by suppression of histone deacetylases and regulation of the mTOR-S6K pathway. Mucosal Immunol. 8: 80-93
77. Berndt, B. E., M. Zhang, S. Y. Owyang, T. S. Cole, T. W. Wang, J. Luther, N. a. Veniaminova, J. L. Merchant, C. C. Chen, G. B. Huffnagle, and J. Y. Kao. 2012. Butyrate increases IL-23 production by stimulated dendritic cells. Am. J. Physiol. Gastrointest. Liver Physiol. 303: G1384-G1392
78. Angulo, P. 2002. Nonalcoholic fatty liver disease. N. Engl. J. Med. 346: 1221-1231
79. Miele, L., V. Valenza, G. La Torre, M. Montalto, G. Cammarota, R. Ricci, R. Mascianè, A. Forgione, M. L. Gabrieli, G. Perotti, et al. 2009. Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. Hepatology 49: 1877-1887
80. Wigg, A. J., I. C. Roberts-Thomson, R. B. Dymock, P. J. McCarthy, R. H. Grose, and A. G. Cummins. 2001. The role of small intestinal bacterial overgrowth, intestinal permeability, endotoxaemia, and tumour necrosis factor alpha in the pathogenesis of non-alcoholic steatohepatitis. Gut 48: 206-211
81. Elinav, E., T. Strowig, A. L. Kau, J. Henao-Mejia, C. A. Thaiss, C. J. Booth, D. R. Peaper, J. Bertin, S. C. Eisenbarth, J. I. Gordon, and R. A. Flavell. 2011. NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell 145: 745-757
82. Henao-Mejia, J., E. Elinav, C. Jin, L. Hao, W. Z. Mehal, T. Strowig, C. A. Thaiss, A. L. Kau, S. C. Eisenbarth, M. J. Jurczak, et al. 2012. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 482: 179-185
83. Jiang, W., N. Wu, X. Wang, Y. Chi, Y. Zhang, X. Qiu, Y. Hu, J. Li, and Y. Liu. 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
84. Thaiss, C. A., N. Zmora, M. Levy, and E. Elinav. 2016. The microbiome and innate immunity. Nature 535: 65-74
85. Lusis, A. J. 2000. Atherosclerosis. Nature 407: 233-241
86. Moore, K. J., F. J. Sheedy, and E. A. Fisher. 2013. Macrophages in atherosclerosis: a dynamic balance. Nat. Rev. Immunol. 13: 709-721
87. Koeth, R. A., Z. Wang, B. S. Levison, J. A. Buffa, E. Org, B. T. Sheehy, E. B. Britt, X. Fu, Y. Wu, L. Li, et al. 2013. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat. Med. 19: 576-585
88. Tang, W. H. W., Z. Wang, B. S. Levison, R. A. Koeth, E. B. Britt, X. Fu, Y. Wu, and S. L. Hazen. 2013. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N. Engl. J. Med. 368: 1575-1584
89. Wang, Z., A. B. Roberts, J. A. Buffa, B. S. Levison, W. Zhu, E. Org, X. Gu, Y. Huang, M. Zamanian-Daryoush, M. K. Culley, et al. 2015. Non-lethal inhibition of gut microbial trimethylamine production for the treatment of atherosclerosis. Cell 163: 1585-1595
90. Tan, J., C. McKenzie, P. J. Vuillermin, G. Goverse, C. G. Vinuesa, R. E. Mebius, L. Macia, and C. R. Mackay. 2016. Dietary fiber and bacterial SCFA enhance oral tolerance and protect against food allergy through diverse cellular pathways. Cell Rep. 15: 2809-2824
91. Erny, D., A. L. Hrabe de Angelis, D. Jaitin, P. Wieghofer, O. Staszewski, E. David, H. Keren-Shaul, T. Mahlakoiv, K. Jakobshagen, T. Buch, et al. 2015. Host microbiota constantly control maturation and function of microglia in the CNS. Nat. Neurosci. 18: 965-977
92. Wakade, C., R. Chong, E. Bradley, B. Thomas, and J. Morgan. 2014. Upregulation of GPR109A in Parkinson's disease. PLoS One 9: e109818
93. Fu, S.-P., J.-F. Wang, W.-J. Xue, H.-M. Liu, B. R. Liu, Y.-L. Zeng, S.-N. Li, B.-X. Huang, Q.-K. Lv, W. Wang, and J.-X. Liu. 2015. Anti-inflammatory effects of BHBA in both in vivo and in vitro Parkinson's disease models are mediated by GPR109A-dependent mechanisms. J. Neuroinflammation 12: 9
94. Sherry, C. L., S. S. Kim, R. N. Dilger, L. L. Bauer, M. L. Moon, R. I. Tapping, G. C. Fahey, Jr., K. A. Tappenden, and G. G. Freund. 2010. Sickness behavior induced by endotoxin can be mitigated by the dietary soluble fiber, pectin, through up-regulation of IL-4 and Th2 polarization. Brain Behav. Immun. 24: 631-640
95. Braniste, V., M. Al-Asmakh, C. Kowal, F. Anuar, A. Abbaspour, M. Toth, A. Korecka, N. Bakocevic, L. G. Ng, P. Kundu, et al. 2014. The gut microbiota influences blood-brain barrier permeability in mice. Sci. Transl. Med. 6: 263ra158
96. Hsiao, E. Y., S. W. McBride, S. Hsien, G. Sharon, E. R. Hyde, T. McCue, J. A. Codelli, J. Chow, S. E. Reisman, J. F. Petrosino, et al. 2013. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 155: 1451-1463
97. Donaldson, G. P., S. M. Lee, and S. K. Mazmanian. 2016. Gut biogeography of the bacterial microbiota. Nat. Rev. Microbiol. 14: 20-32
98. Charbonneau, M. R., D. O'Donnell, L. V. Blanton, S. M. Totten, J. C. C. Davis, M. J. Barratt, J. Cheng, J. Guruge, M. Talcott, J. R. Bain, et al. 2016. Sialylated milk oligosaccharides promote microbiota-dependent growth in models of infant undernutrition. Cell 164: 859-871
99. Zeevi, D., T. Korem, N. Zmora, D. Israeli, D. Rothschild, A. Weinberger, O. Ben-Yacov, D. Lador, T. Avnit-Sagi, M. Lotan-Pompan, et al. 2015. Personalized nutrition by prediction of glycemic responses. Cell 163: 1079-1094.