Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Gut microbiota–generated metabolites in animal health and disease

Nature Chemical Biology volume 10, pages 416–424 (2014)Cite this article

Subjects

Abstract

Gut microbiota is found in virtually any metazoan, from invertebrates to vertebrates. It has long been believed that gut microbiota, more specifically, the activity of the microbiome and its metabolic products, directly influence a variety of aspects in metazoan physiology. However, the exact molecular relationship among microbe-derived gut metabolites, host signaling pathways, and host physiology remains to be elucidated. Here we review recent discoveries regarding the molecular links between gut metabolites and host physiology in different invertebrate and vertebrate animal models. We describe the different roles of gut microbiome activity and their metabolites in regulating distinct host physiology and the molecular mechanisms by which gut metabolites cause physiological homeostasis via regulating specific host signaling pathways. Future studies in this direction using different animal models will provide the key concepts to understanding the evolutionarily conserved chemical dialogues between gut microbiota and metazoan cells and also human diseases associated with gut microbiota and metabolites.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Gut metabolites and metabolism and host longevity in C. elegans.
Figure 2: A model for gut metabolites and dysbiosis in Drosophila.
Figure 3: Physiological and pathological roles of gut microbial metabolites.
Figure 4: Host-microbe interactions mediated by butyrate and niacin.

Similar content being viewed by others

References

  1. Lee, W.J. & Brey, P.T. How microbiomes influence metazoan development: insights from history and Drosophila modeling of gut-microbe interactions. Annu. Rev. Cell Dev. Biol. 29, 571–592 (2013).

    Article  CAS  PubMed  Google Scholar 

  2. Gusarov, I. et al. Bacterial nitric oxide extends the lifespan of C. elegans. Cell 152, 818–830 (2013).

    Article  CAS  PubMed  Google Scholar 

  3. Cabreiro, F. et al. Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism. Cell 153, 228–239 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Buchon, N., Broderick, N.A. & Lemaitre, B. Gut homeostasis in a microbial world: insights from Drosophila melanogaster. Nat. Rev. Microbiol. 11, 615–626 (2013).

    Article  CAS  PubMed  Google Scholar 

  5. Lee, K.A. & Lee, W.J. Drosophila as a model for intestinal dysbiosis and chronic inflammatory diseases. Dev. Comp. Immunol. 42, 102–110 (2014).

    Article  CAS  PubMed  Google Scholar 

  6. Guo, L., Karpac, J., Tran, S.L. & Jasper, H. PGRP-SC2 promotes gut immune homeostasis to limit commensal dysbiosis and extend lifespan. Cell 156, 109–122 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Shin, S.C. et al. Drosophila microbiome modulates host developmental and metabolic homeostasis via insulin signaling. Science 334, 670–674 (2011).

    Article  CAS  PubMed  Google Scholar 

  8. Gems, D. & Partridge, L. Genetics of longevity in model organisms: debates and paradigm shifts. Annu. Rev. Physiol. 75, 621–644 (2013).

    Article  CAS  PubMed  Google Scholar 

  9. Abada, E.A. et al. C. elegans behavior of preference choice on bacterial food. Mol. Cells 28, 209–213 (2009).

    Article  CAS  PubMed  Google Scholar 

  10. Lenaerts, I., Walker, G.A., Van Hoorebeke, L., Gems, D. & Vanfleteren, J.R. Dietary restriction of Caenorhabditis elegans by axenic culture reflects nutritional requirement for constituents provided by metabolically active microbes. J. Gerontol. A Biol. Sci. Med. Sci. 63, 242–252 (2008).

    Article  PubMed  Google Scholar 

  11. Saiki, R. et al. Altered bacterial metabolism, not coenzyme Q content, is responsible for the lifespan extension in Caenorhabditis elegans fed an Escherichia coli diet lacking coenzyme Q. Aging Cell 7, 291–304 (2008).

    Article  CAS  PubMed  Google Scholar 

  12. Tang, W.H. et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N. Engl. J. Med. 368, 1575–1584 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Koeth, R.A. et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat. Med. 19, 576–585 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Yoshimoto, S. et al. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature 499, 97–101 (2013).

    Article  CAS  PubMed  Google Scholar 

  15. Johnson, C.H., Patterson, A.D., Idle, J.R. & Gonzalez, F.J. Xenobiotic metabolomics: major impact on the metabolome. Annu. Rev. Pharmacol. Toxicol. 52, 37–56 (2012).

    Article  CAS  PubMed  Google Scholar 

  16. Nicholson, J.K. & Wilson, I.D. Opinion: understanding 'global' systems biology: metabonomics and the continuum of metabolism. Nat. Rev. Drug Discov. 2, 668–676 (2003).

    Article  CAS  PubMed  Google Scholar 

  17. Mahmood, K., Naeem, M. & Rahimnajjad, N.A. Metformin: the hidden chronicles of a magic drug. Eur. J. Intern. Med. 24, 20–26 (2013).

    Article  CAS  PubMed  Google Scholar 

  18. Pyra, K.A., Saha, D.C. & Reimer, R.A. Prebiotic fiber increases hepatic acetyl CoA carboxylase phosphorylation and suppresses glucose-dependent insulinotropic polypeptide secretion more effectively when used with metformin in obese rats. J. Nutr. 142, 213–220 (2012).

    Article  CAS  PubMed  Google Scholar 

  19. Shin, N.R. et al. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut 63, 727–735 (2014).

    Article  PubMed  Google Scholar 

  20. Anisimov, V.N. et al. Metformin slows down aging and extends life span of female SHR mice. Cell Cycle 7, 2769–2773 (2008).

    Article  CAS  PubMed  Google Scholar 

  21. Onken, B. & Driscoll, M. Metformin induces a dietary restriction–like state and the oxidative stress response to extend C. elegans healthspan via AMPK, LKB1, and SKN-1. PLoS ONE 5, e8758 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Grandison, R.C., Piper, M.D. & Partridge, L. Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila. Nature 462, 1061–1064 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Zimmerman, J.A., Malloy, V., Krajcik, R. & Orentreich, N. Nutritional control of aging. Exp. Gerontol. 38, 47–52 (2003).

    Article  CAS  PubMed  Google Scholar 

  24. Slack, C., Foley, A. & Partridge, L. Activation of AMPK by the putative dietary restriction mimetic metformin is insufficient to extend lifespan in Drosophila. PLoS ONE 7, e47699 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Ryu, J.H. et al. Innate immune homeostasis by the homeobox gene caudal and commensal-gut mutualism in Drosophila. Science 319, 777–782 (2008).

    Article  CAS  PubMed  Google Scholar 

  26. O'Hara, A.M. & Shanahan, F. The gut flora as a forgotten organ. EMBO Rep. 7, 688–693 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Packey, C.D. & Sartor, R.B. Commensal bacteria, traditional and opportunistic pathogens, dysbiosis and bacterial killing in inflammatory bowel diseases. Curr. Opin. Infect. Dis. 22, 292–301 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  28. Kamada, N., Chen, G.Y., Inohara, N. & Nuñez, G. Control of pathogens and pathobionts by the gut microbiota. Nat. Immunol. 14, 685–690 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Lemaitre, B. & Hoffmann, J. The host defense of Drosophila melanogaster. Annu. Rev. Immunol. 25, 697–743 (2007).

    Article  CAS  PubMed  Google Scholar 

  30. Kim, S.H. & Lee, W.J. Role of DUOX in gut inflammation: lessons from Drosophila model of gut-microbiota interactions. Front. Cell. Infect. Microbiol. 3, 116 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  31. Lee, K.-A. et al. Bacterial-derived uracil as a modulator of mucosal immunity and gut-microbe homeostasis in Drosophila. Cell 153, 797–811 (2013).

    Article  CAS  PubMed  Google Scholar 

  32. Bischoff, V. et al. Downregulation of the Drosophila immune response by peptidoglycan-recognition proteins SC1 and SC2. PLoS Pathog. 2, e14 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Paredes, J.C., Welchman, D.P., Poidevin, M. & Lemaitre, B. Negative regulation by amidase PGRPs shapes the Drosophila antibacterial response and protects the fly from innocuous infection. Immunity 35, 770–779 (2011).

    Article  CAS  PubMed  Google Scholar 

  34. Lhocine, N. et al. PIMS modulates immune tolerance by negatively regulating Drosophila innate immune signaling. Cell Host Microbe 4, 147–158 (2008).

    Article  CAS  PubMed  Google Scholar 

  35. Franzenburg, S. et al. Distinct antimicrobial peptide expression determines host species-specific bacterial associations. Proc. Natl. Acad. Sci. USA 110, E3730–E3738 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  36. Cabreiro, F. & Gems, D. Worms need microbes too: microbiota, health and aging in Caenorhabditis elegans. EMBO Mol. Med. 5, 1300–1310 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Bosch, T.C. Cnidarian-microbe interactions and the origin of innate immunity in metazoans. Annu. Rev. Microbiol. 67, 499–518 (2013).

    Article  CAS  PubMed  Google Scholar 

  38. McFall-Ngai, M. et al. Animals in a bacterial world, a new imperative for the life sciences. Proc. Natl. Acad. Sci. USA 110, 3229–3236 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  39. Chu, H. & Mazmanian, S.K. Innate immune recognition of the microbiota promotes host-microbial symbiosis. Nat. Immunol. 14, 668–675 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Storelli, G. et al. Lactobacillus plantarum promotes Drosophila systemic growth by modulating hormonal signals through TOR-dependent nutrient sensing. Cell Metab. 14, 403–414 (2011).

    Article  CAS  PubMed  Google Scholar 

  41. Ley, R.E., Peterson, D.A. & Gordon, J.I. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 124, 837–848 (2006).

    Article  CAS  PubMed  Google Scholar 

  42. Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature 486, 207–214 (2012).

  43. Nicholson, J.K. et al. Host-gut microbiota metabolic interactions. Science 336, 1262–1267 (2012).

    Article  CAS  PubMed  Google Scholar 

  44. Bäckhed, F. et al. The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl. Acad. Sci. USA 101, 15718–15723 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Cummings, J.H. Fermentation in the human large intestine: evidence and implications for health. Lancet 1, 1206–1209 (1983).

    Article  CAS  PubMed  Google Scholar 

  46. Cummings, J.H., Pomare, E.W., Branch, W.J., Naylor, C.P. & Macfarlane, G.T. Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut 28, 1221–1227 (1987).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Donohoe, D.R. et al. The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. Cell Metab. 13, 517–526 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Kuma, A. et al. The role of autophagy during the early neonatal starvation period. Nature 432, 1032–1036 (2004).

    Article  CAS  PubMed  Google Scholar 

  49. Asanuma, N., Kawato, M., Ohkawara, S. & Hino, T. Characterization and transcription of the genes encoding enzymes involved in butyrate production in Butyrivibrio fibrisolvens. Curr. Microbiol. 47, 203–207 (2003).

    Article  CAS  PubMed  Google Scholar 

  50. Cho, I. et al. Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature 488, 621–626 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Ley, R.E. et al. Obesity alters gut microbial ecology. Proc. Natl. Acad. Sci. USA 102, 11070–11075 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Ley, R.E., Turnbaugh, P.J., Klein, S. & Gordon, J.I. Microbial ecology: human gut microbes associated with obesity. Nature 444, 1022–1023 (2006).

    Article  CAS  PubMed  Google Scholar 

  53. Turnbaugh, P.J. et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 1027–1031 (2006).

    Article  PubMed  Google Scholar 

  54. Thangaraju, M. et al. GPR109A is a G protein–coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon. Cancer Res. 69, 2826–2832 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Le Poul, E. et al. Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J. Biol. Chem. 278, 25481–25489 (2003).

    Article  CAS  PubMed  Google Scholar 

  56. Singh, N. et al. Activation of gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity 40, 128–139 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Tunaru, S. et al. PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect. Nat. Med. 9, 352–355 (2003).

    Article  CAS  PubMed  Google Scholar 

  58. Hong, Y.-H. et al. Acetate and propionate short chain fatty acids stimulate adipogenesis via GPCR43. Endocrinology 146, 5092–5099 (2005).

    Article  CAS  PubMed  Google Scholar 

  59. Bjursell, M. et al. Improved glucose control and reduced body fat mass in free fatty acid receptor 2–deficient mice fed a high-fat diet. Am. J. Physiol. Endocrinol. Metab. 300, E211–E220 (2011).

    Article  CAS  PubMed  Google Scholar 

  60. Kimura, I. et al. The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43. Nat. Commun. 4, 1829 (2013).

    Article  CAS  PubMed  Google Scholar 

  61. Tolhurst, G. et al. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G protein–coupled receptor FFAR2. Diabetes 61, 364–371 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Maslowski, K.M. et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 461, 1282–1286 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Garrett, W.S., Gordon, J.I. & Glimcher, L.H. Homeostasis and inflammation in the intestine. Cell 140, 859–870 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Del Rio, D., Borges, G. & Crozier, A. Berry flavonoids and phenolics: bioavailability and evidence of protective effects. Br. J. Nutr. 104 Suppl 3, S67–S90 (2010).

    Article  CAS  PubMed  Google Scholar 

  65. Possemiers, S., Bolca, S., Verstraete, W. & Heyerick, A. The intestinal microbiome: a separate organ inside the body with the metabolic potential to influence the bioactivity of botanicals. Fitoterapia 82, 53–66 (2011).

    Article  CAS  PubMed  Google Scholar 

  66. Brestoff, J.R. & Artis, D. Commensal bacteria at the interface of host metabolism and the immune system. Nat. Immunol. 14, 676–684 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Hooper, L.V. & Macpherson, A.J. Immune adaptations that maintain homeostasis with the intestinal microbiota. Nat. Rev. Immunol. 10, 159–169 (2010).

    Article  CAS  PubMed  Google Scholar 

  68. Bouskra, D. et al. Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis. Nature 456, 507–510 (2008).

    Article  CAS  PubMed  Google Scholar 

  69. Moreau, M.C., Ducluzeau, R., Guy-Grand, D. & Muller, M.C. Increase in the population of duodenal immunoglobulin A plasmocytes in axenic mice associated with different living or dead bacterial strains of intestinal origin. Infect. Immun. 21, 532–539 (1978).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Atarashi, K. et al. Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331, 337–341 (2011).

    Article  CAS  PubMed  Google Scholar 

  71. Atarashi, K. et al. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 500, 232–236 (2013).

    Article  CAS  PubMed  Google Scholar 

  72. Mazmanian, S.K., Liu, C.H., Tzianabos, A.O. & Kasper, D.L. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 122, 107–118 (2005).

    Article  CAS  PubMed  Google Scholar 

  73. Cahenzli, J., Köller, Y., Wyss, M., Geuking, M.B. & McCoy, K.D. Intestinal microbial diversity during early-life colonization shapes long-term IgE levels. Cell Host Microbe 14, 559–570 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Umetsu, D.T., McIntire, J.J., Akbari, O., Macaubas, C. & DeKruyff, R.H. Asthma: an epidemic of dysregulated immunity. Nat. Immunol. 3, 715–720 (2002).

    Article  CAS  PubMed  Google Scholar 

  75. Mazmanian, S.K., Round, J.L. & Kasper, D.L. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453, 620–625 (2008).

    Article  CAS  PubMed  Google Scholar 

  76. Round, J.L. et al. The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota. Science 332, 974–977 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Olszak, T. et al. Microbial exposure during early life has persistent effects on natural killer T cell function. Science 336, 489–493 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. An, D. et al. Sphingolipids from a symbiotic microbe regulate homeostasis of host intestinal natural killer T cells. Cell 156, 123–133 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Kawano, T. et al. CD1d-restricted and TCR-mediated activation of va14 NKT cells by glycosylceramides. Science 278, 1626–1629 (1997).

    Article  CAS  PubMed  Google Scholar 

  80. Greer, R.L., Morgun, A. & Shulzhenko, N. Bridging immunity and lipid metabolism by gut microbiota. J. Allergy Clin. Immunol. 132, 253–262, quiz 263 (2013).

    Article  CAS  PubMed  Google Scholar 

  81. Rossi, M., Amaretti, A. & Raimondi, S. Folate production by probiotic bacteria. Nutrients 3, 118–134 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Kjer-Nielsen, L. et al. MR1 presents microbial vitamin B metabolites to MAIT cells. Nature 491, 717–723 (2012).

    Article  CAS  PubMed  Google Scholar 

  83. Bansal, T., Alaniz, R.C., Wood, T.K. & Jayaraman, A. The bacterial signal indole increases epithelial-cell tight-junction resistance and attenuates indicators of inflammation. Proc. Natl. Acad. Sci. USA 107, 228–233 (2010).

    Article  PubMed  Google Scholar 

  84. Shimada, Y. et al. Commensal bacteria-dependent indole production enhances epithelial barrier function in the colon. PLoS ONE 8, e80604 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  85. Fukuda, S. et al. Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature 469, 543–547 (2011).

    Article  CAS  PubMed  Google Scholar 

  86. Inan, M.S. et al. The luminal short-chain fatty acid butyrate modulates NF-kB activity in a human colonic epithelial cell line. Gastroenterology 118, 724–734 (2000).

    Article  CAS  PubMed  Google Scholar 

  87. Smith, P.M. et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341, 569–573 (2013).

    Article  CAS  PubMed  Google Scholar 

  88. Arpaia, N. et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 504, 451–455 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Sakaguchi, S., Yamaguchi, T., Nomura, T. & Ono, M. Regulatory T cells and immune tolerance. Cell 133, 775–787 (2008).

    Article  CAS  PubMed  Google Scholar 

  90. Furusawa, Y. et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504, 446–450 (2013).

    CAS  PubMed  Google Scholar 

  91. Kim, S.V. et al. GPR15-mediated homing controls immune homeostasis in the large intestine mucosa. Science 340, 1456–1459 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Frank, D.N. et al. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc. Natl. Acad. Sci. USA 104, 13780–13785 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Trompette, A. et al. Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat. Med. 20, 159–166 (2014).

    Article  CAS  PubMed  Google Scholar 

  94. Blumberg, R. & Powrie, F. Microbiota, disease, and back to health: a metastable journey. Sci. Transl. Med. 4, 137rv137 (2012).

    Article  CAS  Google Scholar 

  95. Vijay-Kumar, M. et al. Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science 328, 228–231 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Tillisch, K. et al. Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology 144, 1394–1401 (2013).

    Article  CAS  PubMed  Google Scholar 

  97. Hsiao, E.Y. et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 155, 1451–1463 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Wang, L., Angley, M.T., Gerber, J.P. & Sorich, M.J. A review of candidate urinary biomarkers for autism spectrum disorder. Biomarkers 16, 537–552 (2011).

    Article  CAS  PubMed  Google Scholar 

  99. Donohoe, D.R. et al. The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation. Mol. Cell 48, 612–626 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This study was supported by the National Creative Research Initiative Program (no. 20120000231) from National Research Foundation of Korea to W.-J.L. and the Japan Society for the Promotion of Science (no. 24117723) and the Japan Science and Technology Agency (PRESTO) to K.H.

Author information

Authors and Affiliations

  1. National Creative Research Initiative Center for Symbiosystem and School of Biological Sciences, Seoul National University, Seoul, South Korea

    Won-Jae Lee

  2. Department of Biochemistry, Faculty of Pharmacy, Keio University, Tokyo, Japan

    Koji Hase

  3. International Research and Developmental Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    Koji Hase

Authors
  1. Won-Jae Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Koji Hase
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Won-Jae Lee or Koji Hase.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, WJ., Hase, K. Gut microbiota–generated metabolites in animal health and disease. Nat Chem Biol 10, 416–424 (2014). https://doi.org/10.1038/nchembio.1535

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchembio.1535

This article is cited by

Search

Advanced search

Quick links

Nature Briefing Microbiology

Sign up for the Nature Briefing: Microbiology newsletter — what matters in microbiology research, free to your inbox weekly.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing: Microbiology