Butyrate and other short-chain fatty acids as modulators of immunity: What relevance for health?

Current Opinion in Clinical Nutrition and Metabolic Care

Volumn 13, Issue 6, 2010, Pages 715-721

  Meijer, Kees ^a   De Vos, Paul ^a   Priebe, Marion G ^a  

^a UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

Author keywords

dietary fiber; low grade inflammation; obesity; prebiotics; short chain fatty acids

Indexed keywords

BUTYRIC ACID; C REACTIVE PROTEIN; CYTOKINE; HISTONE DEACETYLASE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 1BETA; INTERLEUKIN 6; PROPIONIC ACID; SHORT CHAIN FATTY ACID; TUMOR NECROSIS FACTOR ALPHA; VASCULAR CELL ADHESION MOLECULE 1;

ADIPOSE TISSUE; ANTIGEN PRESENTING CELL; ANTIINFLAMMATORY ACTIVITY; BLOOD FLOW; CELL ADHESION; CELL DIFFERENTIATION; CELL INFILTRATION; CELL PROLIFERATION; CELL TYPE; CHEMOTAXIS; ENZYME INHIBITION; HUMAN; IMMUNOCOMPETENT CELL; IMMUNOMODULATION; INFLAMMATION; LEUKOCYTE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; T LYMPHOCYTE ACTIVATION; TH1 CELL; TH2 CELL;

ANTI-INFLAMMATORY AGENTS; ANTIGEN-PRESENTING CELLS; BUTYRATES; CELL ADHESION; CHEMOTAXIS; DIETARY FIBER; FATTY ACIDS, VOLATILE; FERMENTATION; HUMANS; IMMUNE SYSTEM; IMMUNOLOGIC FACTORS; INFLAMMATION MEDIATORS; OBESITY; SIGNAL TRANSDUCTION;

EID: 78149285318     PISSN: 13631950     EISSN: 14736519     Source Type: Journal    
DOI: 10.1097/MCO.0b013e32833eebe5     Document Type: Review

References (78)

1. Maachi M, Pieroni L, Bruckert E, et al. Systemic low-grade inflammation is related to both circulating and adipose tissue TNFalpha, leptin and IL-6 levels in obese women. Int J Obes Relat Metab Disord 2004;28:993-997.
2. Dandona P, Ghanim H, Chaudhuri A, et al. Macronutrient intake induces oxidative and inflammatory stress: potential relevance to atherosclerosis and insulin resistance. Exp Mol Med 2010;42:245-253.
3. Kolb H, Mandrup-Poulsen T. The global diabetes epidemic as a consequence of lifestyle-induced low-grade inflammation. Diabetologia 2010;53:10-20.
4. Olefsky JM, Glass CK. Macrophages, inflammation, and insulin resistance. Annu Rev Physiol 2010;72:219-246.
5. Pradhan AD, Manson JE, Rifai N, et al. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 2001;286:327-334.
6. Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000;342:836-843.
7. Ajani UA, Ford ES, Mokdad AH. Dietary fiber and C-reactive protein: findings from national health and nutrition examination survey data. J Nutr 2004;134:1181-1185.
8. Ma Y, Griffith JA, Chasan-Taber L, et al. Association between dietary fiber and serum C-reactive protein. Am J Clin Nutr 2006;83:760-766.
9. Qi L, van Dam RM, Liu S, et al. Whole-grain, bran, and cereal fiber intakes and markers of systemic inflammation in diabetic women. Diabetes Care 2006;29:207-211.
10. Wannamethee SG, Whincup PH, Thomas MC, Sattar N. Associations between dietary fiber and inflammation, hepatic function, and risk of type 2 diabetes in older men: potential mechanisms for the benefits of fiber on diabetes risk. Diabetes Care 2009;32:1823-1825.
11. Vulevic J, Drakoularakou A, Yaqoob P, et al. Modulation of the fecal microflora profile and immune function by a novel trans-galactooligosaccharide mixture (B-GOS) in healthy elderly volunteers. Am J Clin Nutr 2008;88:1438-1446.
12. Guigoz Y, Rochat F, Perruisseau-Carrier G, et al. Effects of oligosaccharide on the faecal flora and nonspecific immune system in elderly people. Nutr Res 2000;22:13-25.
13. Priebe MG, Wang H, Weening D, et al. Factors related to colonic fermentation • of nondigestible carbohydrates of a previous evening meal increase tissue glucose uptake and moderate glucose-associated inflammation. Am J Clin Nutr 2010;91:90-97. A study suggesting a link between colonic fermentation of nondigestible carbohydrates and prevention of glucose-induced inflammation in healthy young individuals.
14. Galisteo M, Duarte J, Zarzuelo A. Effects of dietary fibers on disturbances clustered in the metabolic syndrome. J Nutr Biochem 2008;19:71-84.
15. Seifert S, Watzl B. Inulin and oligofructose: review of experimental data on immune modulation. J Nutr 2007;137:2563S-2567S.
16. Schley PD, Field CJ. The immune-enhancing effects of dietary fibres and prebiotics. Br J Nutr 2002;87:S221-S230.
17. Cummings JH, Pomare EW, Branch WJ, et al. Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut 1987;28:1221-1227.
18. Ghanim H, Aljada A, Hofmeyer D, et al. Circulating mononuclear cells in the obese are in a proinflammatory state. Circulation 2004;110:1564-1571.
19. Deopurkar R, Ghanim H, Friedman J, et al. Differential effects of cream, glucose, and orange juice on inflammation, endotoxin, and the expression of Toll-like receptor-4 and suppressor of cytokine signaling-3. Diabetes Care 2010;33:991-997.
20. Ghanim H, Sia CL, Upadhyay M, et al. Orange juice neutralizes the proinflammatory effect of a high-fat, high-carbohydrate meal and prevents endotoxin increase and Toll-like receptor expression. Am J Clin Nutr 2010;91:940-949.
21. Patel C, Ghanim H, Ravishankar S, et al. Prolonged reactive oxygen species generation and nuclear factor-kappaB activation after a high-fat, highcarbohydrate meal in the obese. J Clin Endocrinol Metab 2007;92:4476-4479.
22. Burdge GC, Calder PC. Plasma cytokine response during the postprandial period: a potential causal process in vascular disease? Br J Nutr 2005;93:3-9.
23. Magne J, Mariotti F, Fischer R, et al. Early postprandial low-grade inflammation after high-fat meal in healthy rats: possible involvement of visceral adipose tissue. J Nutr Biochem 2010;21:550-555.
24. Neels JG, Olefsky JM. Inflamed fat: what starts the fire? J Clin Invest 2006;116:33-35.
25. Fontana L, Eagon JC, Trujillo ME, et al. Visceral fat adipokine secretion is associated with systemic inflammation in obese humans. Diabetes 2007;56:1010-1013.
26. Duffaut C, Zakaroff-Girard A, Bourlier V, et al. Interplay between human adipocytes and T lymphocytes in obesity: CCL20 as an adipochemokine and T lymphocytes as lipogenic modulators. Arterioscler Thromb Vasc Biol 2009;29:1608-1614.
27. reg cells in adipose tissue of obese versus nonobese persons.
28. Winer S, Chan Y, Paltser G, et al. Normalization of obesity-associated insulin • resistance through immunotherapy. Nat Med 2009;15:921-929. An interesting study on the balance of different types of T cells in adipose tissue and effects of obesity on T-cell receptor diversity.
29. Zeyda M, Huber J, Prager G, Stulnig TM. Inflammation correlates with markers of T-cell subsets including regulatory T cells in adipose tissue from obese patients. Obesity (Silver Spring) 2010. [Epub ahead of print]
30. Nishimura S, Manabe I, Nagasaki M, et al. CD8+ effector T cells contribute to • macrophage recruitment and adipose tissue inflammation in obesity. Nat Med 2009;15:914-920. A paper describing the sequence of infiltrating immune cells in obese adipose tissue.
31. Maynard CL, Weaver CT. Intestinal effector T cells in health and disease. Immunity 2009;31:389-400.
32. Brown AJ, Goldsworthy SM, Barnes AA, et al. The orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem 2003;278:11312-11319.
33. Le Poul E, Loison C, Struyf S, et al. Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J Biol Chem 2003;278:25481-25489.
34. Al-Lahham SH, Roelofsen H, Priebe M, et al. Regulation of adipokine production in human adipose tissue by propionic acid. Eur J Clin Invest 2010;40:401-407.
35. -/- mice showing aggravated inflammation.
36. Sina C, Gavrilova O, Forster M, et al. G protein-coupled receptor 43 is essential for neutrophil recruitment during intestinal inflammation. J Immunol 2009;183:7514-7522.
37. Bocker U, Nebe T, Herweck F, et al. Butyrate modulates intestinal epithelial cell-mediated neutrophil migration. Clin Exp Immunol 2003;131:53-60.
38. Vinolo MA, Rodrigues HG, Hatanaka E, et al. Short-chain fatty acids stimulate • the migration of neutrophils to inflammatory sites. Clin Sci (Lond) 2009;117:331-338. A study analyzing SCFA-induced migration of neutrophils and involved adhesion molecules and chemokines.
39. Maa MC, Chang MY, Hsieh MY, et al. Butyrate reduced lipopolysaccharide- •• mediated macrophage migration by suppression of Src enhancement and focal adhesion kinase activity. J Nutr Biochem 2010. [Epub ahead of print] An interesting article on the effect of butyrate on migration of macrophages and underlying mechanisms.
40. Cox MA, Jackson J, Stanton M, et al. Short-chain fatty acids act as antiin-• flammatory mediators by regulating prostaglandin E (2) and cytokines. World J Gastroenterol 2009;15:5549-5557. This article describes the differential anti-inflammatory effects of SCFAs on immune cells.
41. Menzel T, Luhrs H, Zirlik S, et al. Butyrate inhibits leukocyte adhesion to endothelial cells via modulation of VCAM-1. Inflamm Bowel Dis 2004;10:1 22-128.
42. Miller SJ, Zaloga GP, Hoggatt AM, et al. Short-chain fatty acids modulate gene expression for vascular endothelial cell adhesion molecules. Nutrition 2005;21:740-748.
43. Zapolska-Downar D, Siennicka A, Kaczmarczyk M, et al. Butyrate inhibits cytokine-induced VCAM-1 and ICAM-1 expression in cultured endothelial cells: the role of NF-kappaB and PPARalpha. J Nutr Biochem 2004;15:220-228.
44. Zapolska-Downar D, Naruszewicz M. Propionate reduces the cytokine-in-• duced VCAM-1 and ICAM-1 expression by inhibiting nuclear factor-kappa B (NF-kappaB) activation. J Physiol Pharmacol 2009;60:123-131. A study analyzing the effect of propionate on expression of adhesion molecules.
45. Bohmig GA, Krieger PM, Saemann MD, et al. n-butyrate downregulates the stimulatory function of peripheral blood-derived antigen-presenting cells: a potential mechanism for modulating T-cell responses by short-chain fatty acids. Immunology 1997;92:234-243.
46. Roy CC, Kien CL, Bouthillier L, Levy E. Short-chain fatty acids: ready for prime time? Nutr Clin Pract 2006;21:351-366.
47. Eftimiadi C, Buzzi E, Tonetti M, et al. Short-chain fatty acids produced by anaerobic bacteria alter the physiological responses of human neutrophils to chemotactic peptide. J Infect 1987;14:43-53.
48. Eftimiadi C, Tonetti M, Cavallero A, et al. Short-chain fatty acids produced by anaerobic bacteria inhibit phagocytosis by human lung phagocytes. J Infect Dis 1990;161:138-142.
49. Saemann MD, Bohmig GA, Osterreicher CH, et al. Anti-inflammatory effects of sodium butyrate on human monocytes: potent inhibition of IL-12 and upregulation of IL-10 production. FASEB J 2000;14:2380-2382.
50. Park JS, Lee EJ, Lee JC, et al. Anti-inflammatory effects of short chain fatty acids in IFN-gamma-stimulated RAW 264.7 murine macrophage cells: involvement of NF-kappaB and ERK signaling pathways. Int Immunopharmacol 2007;7:70-77.
51. Chakravortty D, Koide N, Kato Y, et al. The inhibitory action of butyrate on lipopolysaccharide-induced nitric oxide production in RAW 264.7 murine macrophage cells. J Endotoxin Res 2000;6:243-247.
52. Stempelj M, Kedinger M, Augenlicht L, Klampfer L. Essential role of the JAK/STAT1 signaling pathway in the expression of inducible nitric-oxide synthase in intestinal epithelial cells and its regulation by butyrate. J Biol Chem 2007;282:9797-9804.
53. Cavaglieri CR, Nishiyama A, Fernandes LC, et al. Differential effects of shortchain fatty acids on proliferation and production of pro-and anti-inflammatory cytokines by cultured lymphocytes. Life Sci 2003;73:1683-1690.
54. Vinolo MA, Hatanaka E, Lambertucci RH, et al. Effects of short chain fatty • acids on effector mechanisms of neutrophils. Cell Biochem Funct 2009;27:48-55. This article describes the effect of butyrate and propionate on effector functions of neutrophils.
55. Tedelind S, Westberg F, Kjerrulf M, Vidal A. Anti-inflammatory properties of the short-chain fatty acids acetate and propionate: a study with relevance to inflammatory bowel disease. World J Gastroenterol 2007;13:2826-2832.
56. Usami M, Kishimoto K, Ohata A, et al. 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 2008;28:321-328.
57. Maier E, Kurz K, Jenny M, et al. Food preservatives sodium benzoate and • propionic acid and colorant curcumin suppress Th1-type immune response in vitro. Food Chem Toxicol 2010;48:1950-1956. A paper on the immune modulatory effects of propionate (as food additive) on PBMCs.
58. Nancey S, Bienvenu J, Coffin B, et al. Butyrate strongly inhibits in vitro stimulated release of cytokines in blood. Dig Dis Sci 2002;47:921-928.
59. Bailón E, Cueto-Sola M, Utrilla P, et al. Butyrate in vitro immune-modulatory •• effects might be mediated through a proliferation-related induction of apoptosis. Immunobiology 2010. [Epub ahead of print] An elegant study investigating the effect of butyrate on activation and apoptosis as well as the dependence of this effect on the proliferation status of cells.
60. Segain JP, Raingeard De La BD, Bourreille A, et al. Butyrate inhibits inflammatory responses through NFkappaB inhibition: implications for Crohn's disease. Gut 2000;47:397-403.
61. Diakos C, Prieschl EE, Saemann M, et al. Novel mode of interference with nuclear factor of activated T-cells regulation in T-cells by the bacterial metabolite n-butyrate. J Biol Chem 2002;277:24243-24251.
62. Davie JR. Inhibition of histone deacetylase activity by butyrate. J Nutr 2003;133:2485S-2493S.
63. Kouraklis G, Theocharis S. Histone deacetylase inhibitors: a novel target of anticancer therapy (review). Oncol Rep 2006;15:489-494.
64. Quivy V, Van LC. Regulation at multiple levels of NF-kappaB-mediated transactivation by protein acetylation. Biochem Pharmacol 2004;68:1221-1229.
65. Han S, Lu J, Zhang Y, et al. HDAC inhibitors TSA and sodium butyrate enhanced the human IL-5 expression by altering histone acetylation status at its promoter region. Immunol Lett 2007;108:143-150.
66. Park GY, Joo M, Pedchenko T, et al. Regulation of macrophage cyclooxygenase-2 gene expression by modifications of histone H3. Am J Physiol Lung Cell Mol Physiol 2004;286:L956-L962.
67. Tong X, Yin L, Giardina C. Butyrate suppresses Cox-2 activation in colon cancer cells through HDAC inhibition. Biochem Biophys Res Commun 2004;317:463-471.
68. Riggs MG, Whittaker RG, Neumann JR, Ingram VM. n-Butyrate causes histone modification in HeLa and Friend erythroleukaemia cells. Nature 1977;268:462-464.
69. Whitlock JP Jr, Augustine R, Schulman H. Calcium-dependent phosphorylation of histone H3 in butyrate-treated HeLa cells. Nature 1980;287:74-76.
70. Darzynkiewicz Z, Traganos F, Xue SB, Melamed MR. Effect of n-butyrate on cell cycle progression and in situ chromatin structure of L1210 cells. Exp Cell Res 1981;136:279-293.
71. Chung YS, Song IS, Erickson RH, et al. Effect of growth and sodium butyrate on brush border membrane-associated hydrolases in human colorectal cancer cell lines. Cancer Res 1985;45:2976-2982.
72. Kruh J. Effects of sodium butyrate, a new pharmacological agent, on cells in culture. Mol Cell Biochem 1982;42:65-82.
73. Comalada M, Valledor AF, Sanchez-Tillo E, et al. Macrophage colony-stimulating factor-dependent macrophage proliferation is mediated through a calcineurin-independent but immunophilin-dependent mechanism that mediates the activation of external regulated kinases. Eur J Immunol 2003;33:3091-3100.
74. Aoyama M, Kotani J, Usami M. Butyrate and propionate induced activated or •• nonactivated neutrophil apoptosis via HDAC inhibitor activity but without activating GPR-41/GPR-43 pathways. Nutrition 2010;26:653-661. This is an interesting paper studying SCFA-induced apoptosis in neutrophils and possible mechanisms.
75. Stehle HW, Leblebicioglu B, Walters JD. Short-chain carboxylic acids produced by Gram-negative anaerobic bacteria can accelerate or delay polymorphonuclear leukocyte apoptosis in vitro. J Periodontol 2001;72:1059-1063.
76. Tao R, de Zoeten EF, Ozkaynak E, et al. Deacetylase inhibition promotes the generation and function of regulatory T cells. Nat Med 2007;13:1299-1307.
77. Wang L, Tao R, Hancock WW. Using histone deacetylase inhibitors to enhance Foxp3 (+) regulatory T-cell function and induce allograft tolerance. Immunol Cell Biol 2009;87:195-202.
78. Izcue A, Coombes JL, Powrie F. Regulatory T cells suppress systemic and mucosal immune activation to control intestinal inflammation. Immunol Rev 2006;212:256-271.