Potential beneficial effects of butyrate in intestinal and extraintestinal diseases

The multiple beneficial effects on human health of the short-chain fatty acid butyrate, synthesized from non-absorbed carbohydrate by colonic microbiota, are well documented. At the intestinal level, butyrate plays a regulatory role on the transepithelial fluid transport, ameliorates mucosal inflammation and oxidative status, reinforces the epithelial defense barrier, and modulates visceral sensitivity and intestinal motility. In addition, a growing number of studies have stressed the role of butyrate in the prevention and inhibition of colorectal cancer. At the extraintestinal level, butyrate exerts potentially useful effects on many conditions, including hemoglobinopathies, genetic metabolic diseases, hypercholesterolemia, insulin resistance, and ischemic stroke. The mechanisms of action of butyrate are different; many of these are related to its potent regulatory effects on gene expression. These data suggest a wide spectrum of positive effects exerted by butyrate, with a high potential for a therapeutic use in human medicine.

[1]  F. Greer,et al.  Probiotics and Prebiotics in Pediatrics , 2010, Pediatrics.

[2]  P. de Vos,et al.  Butyrate and other short-chain fatty acids as modulators of immunity: what relevance for health? , 2010, Current opinion in clinical nutrition and metabolic care.

[3]  B. Corfe,et al.  Butyrate suppresses expression of neuropilin I in colorectal cell lines through inhibition of Sp1 transactivation , 2010, Molecular Cancer.

[4]  P. Guilloteau,et al.  From the gut to the peripheral tissues: the multiple effects of butyrate , 2010, Nutrition Research Reviews.

[5]  K. Tappenden Emerging therapies for intestinal failure. , 2010, Archives of surgery.

[6]  P. de Coppet,et al.  Short-chain fatty acids regulate the enteric neurons and control gastrointestinal motility in rats. , 2010, Gastroenterology.

[7]  Arnaud Bourreille,et al.  Butyrate utilization by the colonic mucosa in inflammatory bowel diseases: A transport deficiency , 2010, Inflammatory bowel diseases.

[8]  H. Binder,et al.  Role of colonic short-chain fatty acid transport in diarrhea. , 2010, Annual review of physiology.

[9]  P. Rosenstiel,et al.  G Protein-Coupled Receptor 43 Is Essential for Neutrophil Recruitment during Intestinal Inflammation1 , 2009, The Journal of Immunology.

[10]  J. Steinmann,et al.  Phenylbutyrate Induces Antimicrobial Peptide Expression , 2009, Antimicrobial Agents and Chemotherapy.

[11]  Ian R. Holzman,et al.  Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. , 2009, The Journal of nutrition.

[12]  D. Jonkers,et al.  The effects of butyrate enemas on visceral perception in healthy volunteers , 2009, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[13]  D. Chuang,et al.  The HDAC inhibitor, sodium butyrate, stimulates neurogenesis in the ischemic brain , 2009, Journal of neurochemistry.

[14]  N. Habermann,et al.  Mechanisms of primary cancer prevention by butyrate and other products formed during gut flora-mediated fermentation of dietary fibre. , 2009, Mutation research.

[15]  Harry J. Flint,et al.  Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine. , 2009, FEMS microbiology letters.

[16]  W. Cefalu,et al.  Butyrate Improves Insulin Sensitivity and Increases Energy Expenditure in Mice , 2009, Diabetes.

[17]  G. Cresci,et al.  GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon. , 2009, Cancer research.

[18]  A. Bast,et al.  Butyrate modulates oxidative stress in the colonic mucosa of healthy humans. , 2009, Clinical nutrition.

[19]  J. Ribalta,et al.  Gene expression analysis of a human enterocyte cell line reveals downregulation of cholesterol biosynthesis in response to short‐chain fatty acids , 2008, IUBMB life.

[20]  C. Lowrey,et al.  A cell stress signaling model of fetal hemoglobin induction: what doesn't kill red blood cells may make them stronger. , 2008, Experimental hematology.

[21]  I. Kaji,et al.  Roles of short-chain fatty acids receptors, GPR41 and GPR43 on colonic functions. , 2008, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[22]  A. Sartorelli,et al.  Butyrate and Wnt signaling: a possible solution to the puzzle of dietary fiber and colon cancer risk? , 2008, Cell cycle.

[23]  D. Jonkers,et al.  Review article: the role of butyrate on colonic function , 2007, Alimentary pharmacology & therapeutics.

[24]  P. Gean,et al.  Valproic acid and other histone deacetylase inhibitors induce microglial apoptosis and attenuate lipopolysaccharide-induced dopaminergic neurotoxicity , 2007, Neuroscience.

[25]  M. Schwab,et al.  Involvement of different nuclear hormone receptors in butyrate-mediated inhibition of inducible NF kappa B signalling. , 2007, Molecular immunology.

[26]  J. Clancy,et al.  Restoration of W1282X CFTR activity by enhanced expression. , 2007, American journal of respiratory cell and molecular biology.

[27]  Tatsuya Abe,et al.  The short chain fatty acid, butyrate, stimulates MUC2 mucin production in the human colon cancer cell line, LS174T. , 2007, Biochemical and biophysical research communications.

[28]  M. Abdollahi,et al.  Oxidative Stress and Pathogenesis of Inflammatory Bowel Disease: An Epiphenomenon or the Cause? , 2007, Digestive Diseases and Sciences.

[29]  B. Corfe,et al.  Upregulation of BAK by butyrate in the colon is associated with increased Sp3 binding , 2006, Oncogene.

[30]  M. Säemann,et al.  n-Butyrate inhibits Jun NH(2)-terminal kinase activation and cytokine transcription in mast cells. , 2006, Biochemical and biophysical research communications.

[31]  M. Gassull Review article: the intestinal lumen as a therapeutic target in inflammatory bowel disease , 2006, Alimentary pharmacology & therapeutics.

[32]  M. Comalada,et al.  The effects of short-chain fatty acids on colon epithelial proliferation and survival depend on the cellular phenotype , 2006, Journal of Cancer Research and Clinical Oncology.

[33]  Takashi Shimizu,et al.  Sodium butyrate up-regulates cathelicidin gene expression via activator protein-1 and histone acetylation at the promoter region in a human lung epithelial cell line, EBC-1. , 2006, Molecular immunology.

[34]  S. Theocharis,et al.  Histone deacetylase inhibitors: a novel target of anticancer therapy (review). , 2006, Oncology reports.

[35]  W. Willett,et al.  Dietary fiber intake and risk of colorectal cancer: a pooled analysis of prospective cohort studies. , 2005, JAMA.

[36]  S. Veeriah,et al.  Modulation of xenobiotic metabolising enzymes by anticarcinogens -- focus on glutathione S-transferases and their role as targets of dietary chemoprevention in colorectal carcinogenesis. , 2005, Mutation research.

[37]  R. Mitsui,et al.  Neural and non‐neural mediation of propionate‐induced contractile responses in the rat distal colon , 2005, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[38]  G. Stamatoyannopoulos,et al.  Butyrate increases the efficiency of translation of γ-globin mRNA , 2005 .

[39]  E. Skrzydlewska,et al.  Lipid peroxidation and antioxidant status in colorectal cancer. , 2005, World journal of gastroenterology.

[40]  W. Riedel,et al.  Acute tryptophan depletion affects brain-gut responses in irritable bowel syndrome patients and controls , 2004, Gut.

[41]  H. Gylling Cholesterol metabolism and its implications for therapeutic interventions in patients with hypercholesterolaemia , 2004, International journal of clinical practice.

[42]  W. Scheppach,et al.  The butyrate story: old wine in new bottles? , 2004, Current opinion in clinical nutrition and metabolic care.

[43]  G. Castaldo,et al.  Butyrate as an effective treatment of congenital chloride diarrhea. , 2004, Gastroenterology.

[44]  H. Lührs,et al.  Histone-deacetylase inhibitors induce the cathelicidin LL-37 in gastrointestinal cells. , 2004, Molecular immunology.

[45]  S. Muallem,et al.  Gating of CFTR by the STAS domain of SLC26 transporters , 2004, Nature Cell Biology.

[46]  Yingxuan Chen,et al.  [Regulation of histone acetylation on the expression of cell cycle-associated genes in human colon cancer cell lines]. , 2004, Zhonghua yi xue za zhi.

[47]  M. Kagnoff,et al.  Expression of LL-37 by human gastric epithelial cells as a potential host defense mechanism against Helicobacter pylori. , 2003, Gastroenterology.

[48]  S. V. van Deventer,et al.  Short chain fatty acids stimulate epithelial mucin 2 expression through differential effects on prostaglandin E(1) and E(2) production by intestinal myofibroblasts. , 2003, Gut.

[49]  L. Augenlicht,et al.  Inhibition of interferon γ signaling by the short chain fatty acid butyrate , 2003 .

[50]  J. Davie Inhibition of histone deacetylase activity by butyrate. , 2003, The Journal of nutrition.

[51]  Paolo Vineis,et al.  Dietary fibre in food and protection against colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC): an observational study , 2003, The Lancet.

[52]  M. Fujimiya,et al.  Short-chain fatty acids stimulate colonic transit via intraluminal 5-HT release in rats. , 2003, American journal of physiology. Regulatory, integrative and comparative physiology.

[53]  S. Freedman,et al.  Acute regulation of the SLC26A3 congenital chloride diarrhoea anion exchanger (DRA) expressed in Xenopus oocytes , 2003, The Journal of physiology.

[54]  H. Lührs,et al.  Expression of the cathelicidin LL-37 is modulated by short chain fatty acids in colonocytes: relevance of signalling pathways , 2003, Gut.

[55]  H. Matsushime,et al.  Molecular identification of nicotinic acid receptor. , 2003, Biochemical and biophysical research communications.

[56]  S. Dowell,et al.  Molecular Identification of High and Low Affinity Receptors for Nicotinic Acid* , 2003, The Journal of Biological Chemistry.

[57]  I. Björck,et al.  Increasing Fecal Butyrate in Ulcerative Colitis Patients by Diet: Controlled Pilot Study , 2003, Inflammatory bowel diseases.

[58]  V. Annese,et al.  Topical butyrate improves efficacy of 5‐ASA in refractory distal ulcerative colitis: results of a multicentre trial , 2003, European journal of clinical investigation.

[59]  E. Levy,et al.  Butyrate induced Caco-2 cell apoptosis is mediated via the mitochondrial pathway , 2003, Gut.

[60]  B. Hinnebusch,et al.  The effects of short-chain fatty acids on human colon cancer cell phenotype are associated with histone hyperacetylation. , 2002, The Journal of nutrition.

[61]  H. Lührs,et al.  Butyrate Inhibits NF-κB Activation in Lamina Propria Macrophages of Patients with Ulcerative Colitis , 2002, Scandinavian journal of gastroenterology.

[62]  J. Kere,et al.  Identification of seven novel mutations including the first two genomic rearrangements in SLC26A3 mutated in congenital chloride diarrhea , 2001, Human mutation.

[63]  G. Rabbani,et al.  Clinical studies in persistent diarrhea: dietary management with green banana or pectin in Bangladeshi children. , 2001, Gastroenterology.

[64]  D. S. Lind,et al.  Nuclear factor-κB is upregulated in colorectal cancer , 2001 .

[65]  A. Burlina,et al.  Long-term treatment with sodium phenylbutyrate in ornithine transcarbamylase-deficient patients. , 2001, Molecular genetics and metabolism.

[66]  J. Galmiche,et al.  Butyrate inhibits inflammatory responses through NFkappaB inhibition: implications for Crohn's disease. , 2000, Gut.

[67]  J. Kere,et al.  Inherited disorders of ion transport in the intestine. , 2000, Current opinion in genetics & development.

[68]  Young-In Kim,et al.  AGA technical review: impact of dietary fiber on colon cancer occurrence. , 2000, Gastroenterology.

[69]  L. Yin,et al.  The luminal short-chain fatty acid butyrate modulates NF-kappaB activity in a human colonic epithelial cell line. , 2000, Gastroenterology.

[70]  R. Sartor,et al.  The IκB/NF-κB system: a key determinant of mucosal inflammation and protection , 2000 .

[71]  J. Roth,et al.  Overexpression of the wild-type p53 gene inhibits NF-κB activity and synergizes with aspirin to induce apoptosis in human colon cancer cells , 2000, Oncogene.

[72]  G. Young,et al.  Amylase-resistant starch plus oral rehydration solution for cholera. , 2000, The New England journal of medicine.

[73]  G. Jacobasch,et al.  Dietary resistant starch and chronic inflammatory bowel diseases , 1999, International Journal of Colorectal Disease.

[74]  M. Albert,et al.  Short-Chain Fatty Acids Inhibit Fluid and Electrolyte Loss Induced by Cholera Toxin in Proximal Colon of Rabbit In Vivo , 1999, Digestive Diseases and Sciences.

[75]  E. Levy,et al.  Butyrate mediates Caco-2 cell apoptosis via up-regulation of pro-apoptotic BAK and inducing caspase-3 mediated cleavage of poly-(ADP-ribose) polymerase (PARP) , 1999, Cell Death and Differentiation.

[76]  Andrew J. Wilson,et al.  Colonic epithelial cell activation and the paradoxical effects of butyrate. , 1999, Carcinogenesis.

[77]  G. Stamatoyannopoulos,et al.  Sustained induction of fetal hemoglobin by pulse butyrate therapy in sickle cell disease. , 1999, Blood.

[78]  A. Moser,et al.  Gene redundancy and pharmacological gene therapy: Implications for X-linked adrenoleukodystrophy , 1998, Nature Medicine.

[79]  R. Knuechel,et al.  Nuclear factor kappaB is activated in macrophages and epithelial cells of inflamed intestinal mucosa. , 1998, Gastroenterology.

[80]  J. Hampe,et al.  Activation of nuclear factor κB in inflammatory bowel disease , 1998, Gut.

[81]  M. Karin,et al.  Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. , 1997, The New England journal of medicine.

[82]  J. Mariadason,et al.  Effect of short-chain fatty acids on paracellular permeability in Caco-2 intestinal epithelium model. , 1997, The American journal of physiology.

[83]  S. Meng,et al.  Cellular growth state differentially regulates enterocyte gene expression in butyrate-treated HT-29 cells. , 1996, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[84]  G. Corrao,et al.  Short‐chain fatty acid topical treatment in distal ulcerative colitis , 1995, Alimentary pharmacology & therapeutics.

[85]  T. Stein,et al.  Comparison of intravenous nutrients on gut mucosal proteins synthesis. , 1994, JPEN. Journal of parenteral and enteral nutrition.

[86]  S. Brusilow,et al.  Induction of fetal hemoglobin production in subjects with sickle cell anemia by oral sodium phenylbutyrate , 1994 .

[87]  S. Bingham,et al.  Starch intake and colorectal cancer risk: an international comparison. , 1994, British Journal of Cancer.

[88]  D. Faller,et al.  A short-term trial of butyrate to stimulate fetal-globin-gene expression in the beta-globin disorders. , 1993, The New England journal of medicine.

[89]  A. Whittemore,et al.  Dietary intake of fiber and decreased risk of cancers of the colon and rectum: evidence from the combined analysis of 13 case-control studies. , 1992, Journal of the National Cancer Institute.

[90]  T. Kirchner,et al.  Effect of butyrate enemas on the colonic mucosa in distal ulcerative colitis. , 1992, Gastroenterology.

[91]  P. Mortensen,et al.  Colonic fermentation to short-chain fatty acids is decreased in antibiotic-associated diarrhea. , 1991, Gastroenterology.

[92]  H. Binder,et al.  Short-chain fatty acids stimulate active sodium and chloride absorption in vitro in the rat distal colon. , 1989, Gastroenterology.

[93]  S. J. Chen,et al.  Butyrate infusions in the ovine fetus delay the biologic clock for globin gene switching. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[94]  D. Sviridov,et al.  Regulation of cholesterol synthesis in isolated epithelial cells of human small intestine , 1986, Lipids.

[95]  D. Burkitt Epidemiology of cancer of the colon and rectum , 1971, Cancer.

[96]  P. Höglund,et al.  Oral butyrate in treatment of congenital chloride diarrhea. , 2008, The American journal of gastroenterology.

[97]  Luying Peng,et al.  Effects of Butyrate on Intestinal Barrier Function in a Caco-2 Cell Monolayer Model of Intestinal Barrier , 2007, Pediatric Research.

[98]  N. Goldstein Serrated pathway and APC (conventional)-type colorectal polyps: molecular-morphologic correlations, genetic pathways, and implications for classification. , 2006, American journal of clinical pathology.

[99]  Sadir J Alrawi,et al.  Aberrant crypt foci. , 2006, Anticancer research.

[100]  N. Alam,et al.  Treatment of Infectious Diarrhea in Children , 2003, Paediatric drugs.

[101]  G. Roomans Pharmacological Approaches to Correcting the Ion Transport Defect in Cystic Fibrosis , 2003, American journal of respiratory medicine : drugs, devices, and other interventions.

[102]  K. Kunzelmann,et al.  Electrolyte transport in the mammalian colon: mechanisms and implications for disease. , 2002, Physiological reviews.

[103]  A. Nairn,et al.  Control of CFTR channel gating by phosphorylation and nucleotide hydrolysis. , 1999, Physiological reviews.

[104]  S. Brusilow,et al.  Oral sodium phenylbutyrate therapy in homozygous beta thalassemia: a clinical trial. , 1995, Blood.

[105]  P. Baeuerle,et al.  Function and activation of NF-kappa B in the immune system. , 1994, Annual review of immunology.