The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition

Proceedings of the National Academy of Sciences of the United States of America

Volumn 111, Issue 6, 2014, Pages 2247-2252

  Chang, Pamela V ^a   Hao, Liming ^a   Offermanns, Stefan ^b   Medzhitov, Ruslan ^a  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b MAX PLANCK INSTITUTE FOR HEART AND LUNG RESEARCH   (Germany)

Author keywords

Inflammation; Microbiome

Indexed keywords

INFLAMMATION; MICROBIOME;

ANIMALS; BONE MARROW CELLS; BUTYRATES; HISTONE DEACETYLASE INHIBITORS; INTESTINES; MACROPHAGES; MICE; RECEPTORS, G-PROTEIN-COUPLED;

EID: 84893859801     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1322269111     Document Type: Article

References (42)

1. Hooper LV, Macpherson AJ (2010) Immune adaptations that maintain homeostasis with the intestinal microbiota. Nat Rev Immunol 10(3):159-169.
2. Garrett WS, Gordon JI, Glimcher LH (2010) Homeostasis and inflammation in the intestine. Cell 140(6):859-870.
3. Honda K, Littman DR (2012) The microbiome in infectious disease and inflammation. Annu Rev Immunol 30:759-795.
4. Cerf-Bensussan N, Gaboriau-Routhiau V (2010) The immune system and the gut microbiota: Friends or foes? Nat Rev Immunol 10(10):735-744.
5. Round JL, Mazmanian SK (2009) The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol 9(5):313-323.
6. Varol C, Zigmond E, Jung S (2010) Securing the immune tightrope: Mononuclear phagocytes in the intestinal lamina propria. Nat Rev Immunol 10(6):415-426.
7. Kaser A, Zeissig S, Blumberg RS (2010) Inflammatory bowel disease. Annu Rev Immunol 28:573-621.
8. Maloy KJ, Powrie F (2011) Intestinal homeostasis and its breakdown in inflammatory bowel disease. Nature 474(7351):298-306.
9. Bandara HM, Lam OL, Jin LJ, Samaranayake L (2012) Microbial chemical signaling: A current perspective. Crit Rev Microbiol 38(3):217-249.
10. Atarashi K, et al. (2008) ATP drives lamina propria T(H)17 cell differentiation. Nature 455(7214):808-812.
11. Louis P, Flint HJ (2009) Diversity, metabolism and microbial ecology of butyrateproducing bacteria from the human large intestine. FEMS Microbiol Lett 294(1): 1-8.
12. Sokol H, et al. (2009) Low counts of Faecalibacterium prausnitzii in colitis microbiota. Inflamm Bowel Dis 15(8):1183-1189.
13. Scheppach W; German-Austrian SCFA Study Group (1996) Treatment of distal ulcerative colitis with short-chain fatty acid enemas. A placebo-controlled trial. Dig Dis Sci 41(11):2254-2259.
14. Maslowski KM, et al. (2009) Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 461(7268):1282-1286.
15. Arpaia N, et al. (2013) Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 504(7480):451-455.
16. Furusawa Y, et al. (2013) Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504(7480):446-450.
17. Atarashi K, et al. (2013) Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 500(7461):232-236.
18. Smith PM, et al. (2013) The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341(6145):569-573.
19. Zigmond E, Jung S (2013) Intestinal macrophages: well educated exceptions from the rule. Trends Immunol 34(4):162-168.
20. Ramirez-Carrozzi VR, et al. (2006) Selective and antagonistic functions of SWI/SNF and Mi-2beta nucleosome remodeling complexes during an inflammatory response. Genes Dev 20(3):282-296.
21. Zigmond E, et al. (2012) Ly6C hi monocytes in the inflamed colon give rise to proinflammatory effector cells and migratory antigen-presenting cells. Immunity 37(6): 1076-1090.
22. Rivollier A, He J, Kole A, Valatas V, Kelsall BL (2012) Inflammation switches the differentiation program of Ly6Chi monocytes from antiinflammatory macrophages to inflammatory dendritic cells in the colon. J Exp Med 209(1):139-155.
23. Medina-Contreras O, et al. (2011) CX3CR1 regulates intestinal macrophage homeostasis, bacterial translocation, and colitogenic Th17 responses in mice. J Clin Invest 121(12):4787-4795.
24. Platt AM, Bain CC, Bordon Y, Sester DP, Mowat AM (2010) An independent subset of TLR expressing CCR2-dependent macrophages promotes colonic inflammation. J Immunol 184(12):6843-6854.
25. Atarashi K, et al. (2011) Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331(6015):337-341.
26. Ritter SL, Hall RA (2009) Fine-tuning of GPCR activity by receptor-interacting proteins. Nat Rev Mol Cell Biol 10(12):819-830.
27. Taggart AK, et al. (2005) (D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. J Biol Chem 280(29):26649-26652.
28. Brown AJ, et al. (2003) The orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem 278(13): 11312-11319.
29. Davie JR (2003) Inhibition of histone deacetylase activity by butyrate. J Nutr 133(7, Suppl):2485S-2493S.
30. Musselman CA, et al. (2009) Binding of the CHD4 PHD2 finger to histone H3 is modulated by covalent modifications. Biochem J 423(2):179-187.
31. Roger T, et al. (2011) Histone deacetylase inhibitors impair innate immune responses to Toll-like receptor agonists and to infection. Blood 117(4):1205-1217.
32. Lin ZQ, Kondo T, Ishida Y, Takayasu T, Mukaida N (2003) Essential involvement of IL-6 in the skin wound-healing process as evidenced by delayed wound healing in IL-6-deficient mice. J Leukoc Biol 73(6):713-721.
33. Kanauchi O, et al. (1999) Germinated barley foodstuffs attenuate colonic mucosal damage and mucosal nuclear factor kappa B activity in a spontaneous colitis model. J Gastroenterol Hepatol 14(12):1173-1179.
34. Lührs H, et al. (2002) Butyrate inhibits NF-kappaB activation in lamina propria macrophages of patients with ulcerative colitis. Scand J Gastroenterol 37(4):458-466.
35. Segain JP, et al. (2000) Butyrate inhibits inflammatory responses through NFkappaB inhibition: Implications for Crohn's disease. Gut 47(3):397-403.
36. Wang Q, et al. (2006) Characterization of monocarboxylate transport in human kidney HK-2 cells. Mol Pharm 3(6):675-685.
37. Stein J, Zores M, Schröder O (2000) Short-chain fatty acid (SCFA) uptake into Caco-2 cells by a pH-dependent and carrier mediated transport mechanism. Eur J Nutr 39(3): 121-125.
38. Cui D, Morris ME (2009) The drug of abuse gamma-hydroxybutyrate is a substrate for sodium-coupled monocarboxylate transporter (SMCT) 1 (SLC5A8): Characterization of SMCT-mediated uptake and inhibition. Drug Metab Dispos 37(7):1404-1410.
39. Hamer HM, et al. (2010) Effect of butyrate enemas on inflammation and antioxidant status in the colonic mucosa of patients with ulcerative colitis in remission. Clin Nutr 29(6):738-744.
40. Tarrerias AL, et al. (2002) Short-chain fatty acid enemas fail to decrease colonic hypersensitivity and inflammation in TNBS-induced colonic inflammation in rats. Pain 100(1-2):91-97.
41. Tebbutt NC, et al. (2002) Reciprocal regulation of gastrointestinal homeostasis by SHP2 and STAT-mediated trefoil gene activation in gp130 mutant mice. Nat Med 8(10):1089-1097.
42. Hoshi N, et al. (2012) MyD88 signalling in colonic mononuclear phagocytes drives colitis in IL-10-deficient mice. Nat Commun 3:1120.