Regulation of inflammation by short chain fatty acids

Marco A R Vinolo, Hosana G Rodrigues, Renato T Nachbar, Rui Curi, Marco A R Vinolo, Hosana G Rodrigues, Renato T Nachbar, Rui Curi

Abstract

The short chain fatty acids (SCFAs) acetate (C(2)), propionate (C(3)) and butyrate (C(4)) are the main metabolic products of anaerobic bacteria fermentation in the intestine. In addition to their important role as fuel for intestinal epithelial cells, SCFAs modulate different processes in the gastrointestinal (GI) tract such as electrolyte and water absorption. These fatty acids have been recognized as potential mediators involved in the effects of gut microbiota on intestinal immune function. SCFAs act on leukocytes and endothelial cells through at least two mechanisms: activation of GPCRs (GPR41 and GPR43) and inhibiton of histone deacetylase (HDAC). SCFAs regulate several leukocyte functions including production of cytokines (TNF-α, IL-2, IL-6 and IL-10), eicosanoids and chemokines (e.g., MCP-1 and CINC-2). The ability of leukocytes to migrate to the foci of inflammation and to destroy microbial pathogens also seems to be affected by the SCFAs. In this review, the latest research that describes how SCFAs regulate the inflammatory process is presented. The effects of these fatty acids on isolated cells (leukocytes, endothelial and intestinal epithelial cells) and, particularly, on the recruitment and activation of leukocytes are discussed. Therapeutic application of these fatty acids for the treatment of inflammatory pathologies is also highlighted.

Keywords: short chain fatty acids; acetate; butyrate; inflammation; leukocytes; neutrophils; propionate.

Figures

Figure 1
Figure 1
Schematic representation of the interaction between gut microbiota and host tissues. Soluble factors (e.g., LPS, flagellin, ATP and short chain fatty acids (SCFAs)) released by gut microbiota modulate host tissues such as pancreas, skeletal muscle (SM), adipose tissue (AT), leukocytes, liver and blood vessels function and may play a role in the development of several diseases including cancer, inflammation and diabetes.
Figure 2
Figure 2
Schematic overview of the signaling pathways activated downstream of GPR43 receptors and representation of the effects of SCFAs through inhibition of histone deacetylase (HDAC) activity (B). GPR43 couples to Gi and Gq proteins, which interact with several proteins including adenylate cyclase, small G proteins (e.g., Rac and Rho), mitogen-activated protein kinases (MAPK), phospholipase C (PLC) and A2 (PLA2), ion channels and transcription factors (A). SCFAs may also act on cells through inhibition of HDAC (B). This class of enzymes, together with histone acetyltransferase (HAT), controls the acetylation state of histones and non-histone proteins and, consequently, modulates the transcription of several genes.

References

    1. O’Hara A.M., Shanahan F. The gut flora as a forgotten organ. EMBO Rep. 2006;7:688–693.
    1. Heijtz R.D., Wang S., Anuar F., Qian Y., Bjorkholm B., Samuelsson A., Hibberd M.L., Forssberg H., Pettersson S. Normal gut microbiota modulates brain development and behavior. Proc. Natl. Acad. Sci. USA. 2011;108:3047–3052.
    1. Vijay-Kumar M., Aitken J.D., Carvalho F.A., Cullender T.C., Mwangi S., Srinivasan S., Sitaraman S.V., Knight R., Ley R.E., Gewirtz A.T. Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science. 2010;328:228–231.
    1. Maslowski K.M., Vieira A.T., Ng A., Kranich J., Sierro F., Yu D., Schilter H.C., Rolph M.S., Mackay F., Artis D., et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature. 2009;461:1282–1286.
    1. Uronis J.M., Muhlbauer M., Herfarth H.H., Rubinas T.C., Jones G.S., Jobin C. Modulation of the intestinal microbiota alters colitis-associated colorectal cancer susceptibility. PLoS One. 2009;4:e6026.
    1. De Filippo C., Cavalieri D., Di Paola M., Ramazzotti M., Poullet J.B., Massart S., Collini S., Pieraccini G., Lionetti P. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc. Natl. Acad. Sci. USA. 2010;107:14691–14696.
    1. Cani P.D., Amar J., Iglesias M.A., Poggi M., Knauf C., Bastelica D., Neyrinck A.M., Fava F., Tuohy K.M., Chabo C., et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007;56:1761–1772.
    1. Atarashi K., Nishimura J., Shima T., Umesaki Y., Yamamoto M., Onoue M., Yagita H., Ishii N., Evans R., Honda K., et al. ATP drives lamina propria T(H)17 cell differentiation. Nature. 2008;455:808–812.
    1. Huda-Faujan N., Abdulamir A.S., Fatimah A.B., Anas O.M., Shuhaimi M., Yazid A.M., Loong Y.Y. The impact of the level of the intestinal short chain Fatty acids in inflammatory bowel disease patients versus healthy subjects. Open Biochem. J. 2010;4:53–58.
    1. Vernia P., Caprilli R., Latella G., Barbetti F., Magliocca F.M., Cittadini M. Fecal lactate and ulcerative colitis. Gastroenterology. 1988;95:1564–1568.
    1. Murphy E.F., Cotter P.D., Healy S., Marques T.M., O’Sullivan O., Fouhy F., Clarke S.F., O’Toole P.W., Quigley E.M., Stanton C., et al. Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models. Gut. 2010;59:1635–1642.
    1. McIntyre A., Gibson P.R., Young G.P. Butyrate production from dietary fibre and protection against large bowel cancer in a rat model. Gut. 1993;34:386–391.
    1. Schwiertz A., Taras D., Schafer K., Beijer S., Bos N.A., Donus C., Hardt P.D. Microbiota and SCFA in lean and overweight healthy subjects. Obesity. 2010;18:190–195.
    1. 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. 1987;28:1221–1227. doi: 10.1136/gut.28.10.1221.
    1. McNeil N.I. The contribution of the large intestine to energy supplies in man. Am. J. Clin. Nutr. 1984;39:338–342.
    1. Zaibi M.S., Stocker C.J., O’Dowd J., Davies A., Bellahcene M., Cawthorne M.A., Brown A.J., Smith D.M., Arch J.R. Roles of GPR41 and GPR43 in leptin secretory responses of murine adipocytes to short chain fatty acids. FEBS Lett. 2010;584:2381–2386.
    1. Plaisancie P., Dumoulin V., Chayvialle J.A., Cuber J.C. Luminal peptide YY-releasing factors in the isolated vascularly perfused rat colon. J. Endocrinol. 1996;151:421–429.
    1. Vinolo M.A., Rodrigues H.G., Hatanaka E., Sato F.T., Sampaio S.C., Curi R. Suppressive effect of short-chain fatty acids on production of proinflammatory mediators by neutrophils. J. Nutr. Biochem. 2011;22:849–855.
    1. Luster A.D., Alon R., von Andrian U.H. Immune cell migration in inflammation: present and future therapeutic targets. Nat. Immunol. 2005;6:1182–1190.
    1. Vinolo M.A., Rodrigues H.G., Hatanaka E., Hebeda C.B., Farsky S.H., Curi R. Short-chain fatty acids stimulate the migration of neutrophils to inflammatory sites. Clin. Sci. 2009;117:331–338.
    1. Vinolo M.A., Rodrigues H.G., Hatanaka E., Sato F.T., Sampaio S.C., Curi R. Suppressive effect of short chain fatty acids on production of proinflammatory mediators by neutrophils. J. Nutr. Biochem. 2011;22:849–855.
    1. Le Poul E., Loison C., Struyf S., Springael J.Y., Lannoy V., Decobecq M.E., Brezillon S., Dupriez V., Vassart G., Van Damme J., 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.
    1. Park J.S., Lee E.J., Lee J.C., Kim W.K., Kim H.S. 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. doi: 10.1016/j.intimp.2006.08.015.
    1. Sina C., Gavrilova O., Forster M., Till A., Derer S., Hildebrand F., Raabe B., Chalaris A., Scheller J., Rehmann A., et al. G protein-coupled receptor 43 is essential for neutrophil recruitment during intestinal inflammation. J. Immunol. 2009;183:7514–7522.
    1. Vinolo M.A., Ferguson G.J., Kulkarni S., Damoulakis G., Anderson K., Bohlooly Y.M., Stephens L., Hawkins P.T., Curi R. SCFAs Induce Mouse Neutrophil Chemotaxis through the GPR43 Receptor. PLoS One. 2011;6:e21205.
    1. Brown A.J., Goldsworthy S.M., Barnes A.A., Eilert M.M., Tcheang L., Daniels D., Muir A.I., Wigglesworth M.J., Kinghorn I., Fraser N.J., 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.
    1. Nilsson N.E., Kotarsky K., Owman C., Olde B. Identification of a free fatty acid receptor, FFA2R, expressed on leukocytes and activated by short-chain fatty acid. Biochem. Biophys. Res. Commun. 2003;303:1047–1052.
    1. Itoh Y., Kawamata Y., Harada M., Kobayashi M., Fujii R., Fukusumi S., Ogi K., Hosoya M., Tanaka Y., Uejima H., et al. Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40. Nature. 2003;422:173–176.
    1. Maa M.C., Chang M.Y., Hsieh M.Y., Chen Y.J., Yang C.J., Chen Z.C., Li Y.K., Yen C.K., Wu R.R., Leu T.H. Butyrate reduced lipopolysaccharide-mediated macrophage migration by suppression of Src enhancement and focal adhesion kinase activity. J. Nutr. Biochem. 2010;21:1186–1192.
    1. Owen K.A., Pixley F.J., Thomas K.S., Vicente-Manzanares M., Ray B.J., Horwitz A.F., Parsons J.T., Beggs H.E., Stanley E.R., Bouton A.H. Regulation of lamellipodial persistence, adhesion turnover, and motility in macrophages by focal adhesion kinase. J. Cell Biol. 2007;179:1275–1287.
    1. Zapolska-Downar D., Naruszewicz M. Propionate reduces the cytokine-induced VCAM-1 and ICAM-1 expression by inhibiting nuclear factor-kappa B (NF-kappaB) activation. J. Physiol. Pharmacol. 2009;60:123–131.
    1. Zapolska-Downar D., Siennicka A., Kaczmarczyk M., Kolodziej B., Naruszewicz M. 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.
    1. Miller S.J., Zaloga G.P., Hoggatt A.M., Labarrere C., Faulk W.P. Short-chain fatty acids modulate gene expression for vascular endothelial cell adhesion molecules. Nutrition. 2005;21:740–748.
    1. Cox M.A., Jackson J., Stanton M., Rojas-Triana A., Bober L., Laverty M., Yang X., Zhu F., Liu J., Wang S., et al. Short-chain fatty acids act as antiinflammatory mediators by regulating prostaglandin E(2) and cytokines. World J. Gastroenterol. 2009;15:5549–5557.
    1. Blais M., Seidman E.G., Asselin C. Dual effect of butyrate on IL-1beta-mediated intestinal epithelial cell inflammatory response. DNA Cell Biol. 2007;26:133–147.
    1. Leung C.H., Lam W., Ma D.L., Gullen E.A., Cheng Y.C. Butyrate mediates nucleotide-binding and oligomerisation domain (NOD) 2-dependent mucosal immune responses against peptidoglycan. Eur. J. Immunol. 2009;39:3529–3537.
    1. Bocker U., Nebe T., Herweck F., Holt L., Panja A., Jobin C., Rossol S., Sartor R.B., Singer M.V. Butyrate modulates intestinal epithelial cell-mediated neutrophil migration. Clin. Exp. Immunol. 2003;131:53–60.
    1. Fusunyan R.D., Quinn J.J., Fujimoto M., MacDermott R.P., Sanderson I.R. Butyrate switches the pattern of chemokine secretion by intestinal epithelial cells through histone acetylation. Mol. Med. 1999;5:631–640.
    1. Inatomi O., Andoh A., Kitamura K., Yasui H., Zhang Z., Fujiyama Y. Butyrate blocks interferon-gamma-inducible protein-10 release in human intestinal subepithelial myofibroblasts. J. Gastroenterol. 2005;40:483–489.
    1. Menzel T., Luhrs H., Zirlik S., Schauber J., Kudlich T., Gerke T., Gostner A., Neumann M., Melcher R., Scheppach W. Butyrate inhibits leukocyte adhesion to endothelial cells via modulation of VCAM-1. Inflamm. Bowel Dis. 2004;10:122–128.
    1. Bohmig G.A., Krieger P.M., Saemann M.D., Wenhardt C., Pohanka E., Zlabinger G.J. 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.
    1. Dianzani C., Cavalli R., Zara G.P., Gallicchio M., Lombardi G., Gasco M.R., Panzanelli P., Fantozzi R. Cholesteryl butyrate solid lipid nanoparticles inhibit adhesion of human neutrophils to endothelial cells. Br. J. Pharmacol. 2006;148:648–656.
    1. Allport J.R., Ding H.T., Ager A., Steeber D.A., Tedder T.F., Luscinskas F.W. L-selectin shedding does not regulate human neutrophil attachment, rolling, or transmigration across human vascular endothelium in vitro. J. Immunol. 1997;158:4365–4372.
    1. Olefsky J.M., Glass C.K. Macrophages, inflammation, and insulin resistance. Annu. Rev. Physiol. 2010;72:219–246.
    1. Kinne R.W., Brauer R., Stuhlmuller B., Palombo-Kinne E., Burmester G.R. Macrophages in rheumatoid arthritis. Arthritis Res. 2000;2:189–202.
    1. Griffin W.S. Inflammation and neurodegenerative diseases. Am. J. Clin. Nutr. 2006;83:470S–474S.
    1. Boyle J.J. Macrophage activation in atherosclerosis: Pathogenesis and pharmacology of plaque rupture. Curr. Vasc. Pharmacol. 2005;3:63–68.
    1. Chakravortty D., Koide N., Kato Y., Sugiyama T., Mu M.M., Yoshida T., Yokochi T. 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.
    1. Usami M., Kishimoto K., Ohata A., Miyoshi M., Aoyama M., Fueda Y., Kotani J. 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.
    1. Fukae J., Amasaki Y., Yamashita Y., Bohgaki T., Yasuda S., Jodo S., Atsumi T., Koike T. Butyrate suppresses tumor necrosis factor alpha production by regulating specific messenger RNA degradation mediated through a cis-acting AU-rich element. ArthritisRheum. 2005;52:2697–2707.
    1. Saemann M.D., Bohmig G.A., Osterreicher C.H., Burtscher H., Parolini O., Diakos C., Stockl J., Horl W.H., Zlabinger G.J. Anti-inflammatory effects of sodium butyrate on human monocytes: Potent inhibition of IL-12 and up-regulation of IL-10 production. FASEB J. 2000;14:2380–2382.
    1. Huuskonen J., Suuronen T., Nuutinen T., Kyrylenko S., Salminen A. Regulation of microglial inflammatory response by sodium butyrate and short-chain fatty acids. Br. J. Pharmacol. 2004;141:874–880.
    1. Park J.S., Woo M.S., Kim S.Y., Kim W.K., Kim H.S. Repression of interferon-gamma-induced inducible nitric oxide synthase (iNOS) gene expression in microglia by sodium butyrate is mediated through specific inhibition of ERK signaling pathways. J. Neuroimmunol. 2005;168:56–64.
    1. Chen P.S., Wang C.C., Bortner C.D., Peng G.S., Wu X., Pang H., Lu R.B., Gean P.W., Chuang D.M., Hong J.S. Valproic acid and other histone deacetylase inhibitors induce microglial apoptosis and attenuate lipopolysaccharide-induced dopaminergic neurotoxicity. Neuroscience. 2007;149:203–212.
    1. Perez R., Stevenson F., Johnson J., Morgan M., Erickson K., Hubbard N.E., Morand L., Rudich S., Katznelson S., German J.B. Sodium butyrate upregulates Kupffer cell PGE2 production and modulates immune function. J. Surg. Res. 1998;78:1–6.
    1. Waldecker M., Kautenburger T., Daumann H., Busch C., Schrenk D. Inhibition of histone-deacetylase activity by short-chain fatty acids and some polyphenol metabolites formed in the colon. J. Nutr. Biochem. 2008;19:587–593.
    1. Glozak M.A., Sengupta N., Zhang X., Seto E. Acetylation and deacetylation of non-histone proteins. Gene. 2005;363:15–23.
    1. Cox H.M., Tough I.R., Woolston A.M., Zhang L., Nguyen A.D., Sainsbury A., Herzog H. Peptide YY is critical for acylethanolamine receptor Gpr119-induced activation of gastrointestinal mucosal responses. Cell Metab. 2010;11:532–542.
    1. Yao C., Sakata D., Esaki Y., Li Y., Matsuoka T., Kuroiwa K., Sugimoto Y., Narumiya S. Prostaglandin E2-EP4 signaling promotes immune inflammation through Th1 cell differentiation and Th17 cell expansion. Nat. Med. 2009;15:633–640.
    1. Sakata D., Yao C., Narumiya S. Prostaglandin E2, an immunoactivator. J. Pharmacol. Sci. 2010;112:1–5.
    1. Serhan C.N., Krishnamoorthy S., Recchiuti A., Chiang N. Novel anti-inflammatory-pro-resolving mediators and their receptors. Curr. Top. Med. Chem. 2011;11:629–647.
    1. 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.
    1. Nakamura Y. Regulating factors for microglial activation. Biol. Pharm. Bull. 2002;25:945–953.
    1. Kim H.J., Rowe M., Ren M., Hong J.S., Chen P.S., Chuang D.M. Histone deacetylase inhibitors exhibit anti-inflammatory and neuroprotective effects in a rat permanent ischemic model of stroke: Multiple mechanisms of action. J. Pharmacol. Exp. Ther. 2007;321:892–901.
    1. Vinolo M.A., Hatanaka E., Lambertucci R.H., Newsholme P., Curi R. Effects of short chain fatty acids on effector mechanisms of neutrophils. Cell Biochem. Funct. 2009;27:48–55.
    1. Mills S.W., Montgomery S.H., Morck D.W. Evaluation of the effects of short-chain fatty acids and extracellular pH on bovine neutrophil function in vitro. Am. J. Vet. Res. 2006;67:1901–1907.
    1. Eftimiadi C., Buzzi E., Tonetti M., Buffa P., Buffa D., van Steenbergen M.T., de Graaff J., Botta G.A. Short-chain fatty acids produced by anaerobic bacteria alter the physiological responses of human neutrophils to chemotactic peptide. J. Infect. 1987;14:43–53.
    1. Eftimiadi C., Tonetti M., Cavallero A., Sacco O., Rossi G.A. Short-chain fatty acids produced by anaerobic bacteria inhibit phagocytosis by human lung phagocytes. J. Infect. Dis. 1990;161:138–142.
    1. Millard A.L., Mertes P.M., Ittelet D., Villard F., Jeannesson P., Bernard J. Butyrate affects differentiation, maturation and function of human monocyte-derived dendritic cells and macrophages. Clin. Exp. Immunol. 2002;130:245–255.
    1. Stringer R.E., Hart C.A., Edwards S.W. Sodium butyrate delays neutrophil apoptosis: Role of protein biosynthesis in neutrophil survival. Br. J. Haematol. 1996;92:169–175.
    1. Nakao S., Moriya Y., Furuyama S., Niederman R., Sugiya H. Propionic acid stimulates superoxide generation in human neutrophils. Cell Biol. Int. 1998;22:331–337.
    1. Tonetti M., Cavallero A., Botta G.A., Niederman R., Eftimiadi C. Intracellular pH regulates the production of different oxygen metabolites in neutrophils: Effects of organic acids produced by anaerobic bacteria. J. Leukoc. Biol. 1991;49:180–188.
    1. Liu Q., Shimoyama T., Suzuki K., Umeda T., Nakaji S., Sugawara K. Effect of sodium butyrate on reactive oxygen species generation by human neutrophils. Scand. J. Gastroenterol. 2001;36:744–750.
    1. Sandoval A., Trivinos F., Sanhueza A., Carretta D., Hidalgo M.A., Hancke J.L., Burgos R.A. Propionate induces pH(i) changes through calcium flux, ERK1/2, p38, and PKC in bovine neutrophils. Vet. Immunol. Immunopathol. 2007;115:286–298. doi: 10.1016/j.vetimm.2006.11.003.
    1. Cavaglieri C.R., Nishiyama A., Fernandes L.C., Curi R., Miles E.A., Calder P.C. Differential effects of short-chain fatty acids on proliferation and production of pro- and anti-inflammatory cytokines by cultured lymphocytes. Life Sci. 2003;73:1683–1690.
    1. Dagtas A.S., Edens R.E., Gilbert K.M. Histone deacetylase inhibitor uses p21(Cip1) to maintain anergy in CD4+ T cells. Int. Immunopharmacol. 2009;9:1289–1297.
    1. Tao R., de Zoeten E.F., Ozkaynak E., Chen C., Wang L., Porrett P.M., Li B., Turka L.A., Olson E.N., Greene M.I., Wells A.D., Hancock W.W. Deacetylase inhibition promotes the generation and function of regulatory T cells. Nat. Med. 2007;13:1299–1307.
    1. Jacobasch G., Schmiedl D., Kruschewski M., Schmehl K. Dietary resistant starch and chronic inflammatory bowel diseases. Int. J. Colorectal Dis. 1999;14:201–211.
    1. Nishimura T., Andoh A., Hashimoto T., Kobori A., Tsujikawa T., Fujiyama Y. Cellobiose prevents the development of dextran sulfate sodium (DSS)-induced experimental colitis. J. Clin. Biochem. Nutr. 2010;46:105–110.
    1. Rodriguez-Cabezas M.E., Galvez J., Lorente M.D., Concha A., Camuesco D., Azzouz S., Osuna A., Redondo L., Zarzuelo A. Dietary fiber down-regulates colonic tumor necrosis factor alpha and nitric oxide production in trinitrobenzenesulfonic acid-induced colitic rats. J. Nutr. 2002;132:3263–3271.
    1. Tarrerias A.L., Millecamps M., Alloui A., Beaughard C., Kemeny J.L., Bourdu S., Bommelaer G., Eschalier A., Dapoigny M., Ardid D. Short-chain fatty acid enemas fail to decrease colonic hypersensitivity and inflammation in TNBS-induced colonic inflammation in rats. Pain. 2002;100:91–97.
    1. Scheppach W., Sommer H., Kirchner T., Paganelli G.M., Bartram P., Christl S., Richter F., Dusel G., Kasper H. Effect of butyrate enemas on the colonic mucosa in distal ulcerative colitis. Gastroenterology. 1992;103:51–56.
    1. Hamer H.M., Jonkers D.M., Vanhoutvin S.A., Troost F.J., Rijkers G., de Bruine A., Bast A., Venema K., Brummer R.J. Effect of butyrate enemas on inflammation and antioxidant status in the colonic mucosa of patients with ulcerative colitis in remission. Clin. Nutr. 2010;29:738–744.
    1. Vernia P., Annese V., Bresci G., d’Albasio G., D’Inca R., Giaccari S., Ingrosso M., Mansi C., Riegler G., Valpiani D., et al. Topical butyrate improves efficacy of 5-ASA in refractory distal ulcerative colitis: results of a multicentre trial. Eur. J. Clin. Invest. 2003;33:244–248. doi: 10.1046/j.1365-2362.2003.01130.x.
    1. Vieira E.L, Leonel A.J., Sad A.P., Beltrao N.R., Costa T.F., Ferreira T.M., Gomes-Santos A.C., Faria A.M., Peluzio M.C., Cara D.C., et al. Oral admisnistration of sodium butyrate attenuates inflammation and mucosal lesion in experimental acute ulcerative colitis. J. Nutr. Biochem. 2011 doi: 10.1016/j.jnutbio.2011.01.007..
    1. Zhang L.T., Yao Y.M., Lu J.Q., Yan X.J., Yu Y., Sheng Z.Y. Sodium butyrate prevents lethality of severe sepsis in rats. Shock. 2007;27:672–677.
    1. Ni Y.F., Wang J., Yan X.L., Tian F., Zhao J.B., Wang Y.J., Jiang T. Histone deacetylase inhibitor, butyrate, attenuates lipopolysaccharide-induced acute lung injury in mice. Respir. Res. 2010;11:33. doi: 10.1186/1465-9921-11-33.
    1. Zhang L., Jin S., Wang C., Jiang R., Wan J. Histone deacetylase inhibitors attenuate acute lung injury during cecal ligation and puncture-induced polymicrobial sepsis. World J. Surg. 2010;34:1676–1683.
    1. Hu X., Xu C., Zhou X., He B., Wu L., Cui B., Lu Z., Jiang H. Sodium butyrate protects against myocardial ischemia and reperfusion injury by inhibiting high mobility group box 1 protein in rats. Biomed. Pharmacother. 2010 doi: 10.1016/j.biopha.2010.09.005..
    1. Weber T.E., Kerr B.J. Effect of sodium butyrate on growth performance and response to lipopolysaccharide in weanling pigs. J. Anim. Sci. 2008;86:442–450.
    1. Wang H., Bloom O., Zhang M., Vishnubhakat J.M., Ombrellino M., Che J., Frazier A., Yang H., Ivanova S., Borovikova L., et al. HMG-1 as a late mediator of endotoxin lethality in mice. Science. 1999;285:248–251.
    1. Ulloa L., Tracey K.J. The “cytokine profile”: A code for sepsis. Trends Mol. Med. 2005;11:56–63.
    1. Zhang L., Jin S., Wang C., Jiang R., Wan J. Histone deacetylase inhibitors attenuate acute lung injury during cecal ligation and puncture-induced polymicrobial sepsis. World J. Surg. 2010;34:1676–1683.
    1. Ware L.B., Matthay M.A. The acute respiratory distress syndrome. N. Engl. J. Med. 2000;342:1334–1349.
    1. Balibrea J.L., Arias-Diaz J. Acute respiratory distress syndrome in the septic surgical patient. World J. Surg. 2003;27:1275–1284.
    1. Kurita-Ochiai T., Ochiai K., Fukushima K. Butyric acid-induced T-cell apoptosis is mediated by caspase-8 and -9 activation in a Fas-independent manner. Clin. Diagn. Lab. Immunol. 2001;8:325–332.
    1. Bailon E., Cueto-Sola M., Utrilla P., Rodriguez-Cabezas M.E., Garrido-Mesa N., Zarzuelo A., Xaus J., Galvez J., Comalada M. Butyrate in vitro immune-modulatory effects might be mediated through a proliferation-related induction of apoptosis. Immunobiology. 2010;215:863–873.
    1. Ramos M.G., Rabelo F.L., Duarte T., Gazzinelli R.T., Alvarez-Leite J.I. Butyrate induces apoptosis in murine macrophages via caspase-3, but independent of autocrine synthesis of tumor necrosis factor and nitric oxide. Braz. J. Med. Biol. Res. 2002;35:161–173.
    1. Aoyama M., Kotani J., Usami M. Butyrate and propionate induced activated or non-activated neutrophil apoptosis via HDAC inhibitor activity but without activating GPR-41/GPR-43 pathways. Nutrition. 2010;26:653–661.
    1. Niederman R., Buyle-Bodin Y., Lu B.Y., Robinson P., Naleway C. Short-chain carboxylic acid concentration in human gingival crevicular fluid. J. Dent. Res. 1997;76:575–579.
    1. Halili M.A., Andrews M.R., Labzin L.I., Schroder K., Matthias G., Cao C., Lovelace E., Reid R.C., Le G.T., Hume D.A., et al. Differential effects of selective HDAC inhibitors on macrophage inflammatory responses to the Toll-like receptor 4 agonist LPS. J. Leukoc. Biol. 2010;87:1103–1114. doi: 10.1189/jlb.0509363.

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