Tuning constitutive and pathological inflammation in the gut via the interaction of dietary nitrate and polyphenols with host microbiome

Ahn, 2013, Human gut microbiome and risk for colorectal cancer, J. Natl. Cancer Inst., 105, 1907, 10.1093/jnci/djt300 Al-Sadi, 2009, Mechanism of cytokine modulation of epithelial tight junction barrier, Front. Biosci. (Landmark Ed.), 14, 2765, 10.2741/3413 Al-Sadi, 2013, TNF-alpha modulation of intestinal epithelial tight junction barrier is regulated by ERK1/2 activation of Elk-1, Am. J. Pathol., 183, 1871, 10.1016/j.ajpath.2013.09.001 Amasheh, 2008, Quercetin enhances epithelial barrier function and increases claudin-4 expression in Caco-2 cells, J. Nutr., 138, 1067, 10.1093/jn/138.6.1067 Amiot, 2016, Effects of dietary polyphenols on metabolic syndrome features in humans: a systematic review, Obes. Rev., 17, 573, 10.1111/obr.12409 Amor, 2014, Inflammation in neurodegenerative diseases–an update, Immunology, 142, 151, 10.1111/imm.12233 Anderson, 2009, Physiology and function of the tight junction, Cold Spring Harb. Perspect. Biol., 1, a002584, 10.1101/cshperspect.a002584 Andujar, 2011, Inhibition of ulcerative colitis in mice after oral administration of a polyphenol-enriched cocoa extract is mediated by the inhibition of STAT1 and STAT3 phosphorylation in colon cells, J. Agric. Food Chem., 59, 6474, 10.1021/jf2008925 Armstrong, 2000, Oral administration of inducible nitric oxide synthase inhibitors reduces nitric oxide synthesis but has no effect on the severity of experimental colitis, Scand. J. Gastroenterol., 35, 832, 10.1080/003655200750023200 Ashida, 2012, Bacteria and host interactions in the gut epithelial barrier, Nat. Chem. Biol., 8, 36, 10.1038/nchembio.741 Atreya, 2008, NF-kappaB in inflammatory bowel disease, J. Intern. Med., 263, 591, 10.1111/j.1365-2796.2008.01953.x Babu, 2013, Recent advances in understanding the anti-diabetic actions of dietary flavonoids, J. Nutr. Biochem., 24, 1777, 10.1016/j.jnutbio.2013.06.003 Balogun, 2003, Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element, Biochem. J., 371, 887, 10.1042/bj20021619 Benjamin, 1994, Stomach NO synthesis, Nature, 368, 502, 10.1038/368502a0 Bik, 2006, Molecular analysis of the bacterial microbiota in the human stomach, Proc. Natl. Acad. Sci. U. S. A., 103, 732, 10.1073/pnas.0506655103 Bjorne, 2004, Nitrite in saliva increases gastric mucosal blood flow and mucus thickness, J. Clin. Invest., 113, 106, 10.1172/JCI19019 Bjornsson, 2015, Nitrite, a novel method to decrease ischemia/reperfusion injury in the rat liver, World J. Gastroenterol., 21, 1775, 10.3748/wjg.v21.i6.1775 Bonacci, 2012, Conjugated linoleic acid is a preferential substrate for fatty acid nitration, J. Biol. Chem., 287, 44071, 10.1074/jbc.M112.401356 Bonaz, 2013, Brain-gut interactions in inflammatory bowel disease, Gastroenterology, 144, 36, 10.1053/j.gastro.2012.10.003 Borniquel, 2010, Nitrated oleic acid up-regulates PPARgamma and attenuates experimental inflammatory bowel disease, Free Radic. Biol. Med., 48, 499, 10.1016/j.freeradbiomed.2009.11.014 Cani, 2007, Metabolic endotoxemia initiates obesity and insulin resistance, Diabetes, 56, 1761, 10.2337/db06-1491 Cardona, 2013, Benefits of polyphenols on gut microbiota and implications in human health, J. Nutr. Biochem., 24, 1415, 10.1016/j.jnutbio.2013.05.001 Cheynier, 2005, Polyphenols in foods are more complex than often thought, Am. J. Clin. Nutr., 81, 223S, 10.1093/ajcn/81.1.223S Chuenkitiyanon, 2010, Protective effect of quercetin on hydrogen peroxide-induced tight junction disruption, Int. J. Toxicol., 29, 418, 10.1177/1091581810366487 Claesson, 2012, Gut microbiota composition correlates with diet and health in the elderly, Nature, 488, 178, 10.1038/nature11319 Contreras, 2015, (−)-Epicatechin in the prevention of tumor necrosis alpha-induced loss of Caco-2 cell barrier integrity, Arch. Biochem. Biophys., 573, 84, 10.1016/j.abb.2015.01.024 Coskun, 2013, Involvement of JAK/STAT signaling in the pathogenesis of inflammatory bowel disease, Pharmacol. Res., 76, 1, 10.1016/j.phrs.2013.06.007 Coskun, 2014, Intestinal epithelium in inflammatory bowel disease, Front. Med. (Lausanne), 1, 24 Cuervo, 2015, Red wine consumption is associated with fecal microbiota and malondialdehyde in a human population, J. Am. Coll. Nutr., 34, 135, 10.1080/07315724.2014.904763 Cui, 2014, The anti-inflammation effect of baicalin on experimental colitis through inhibiting TLR4/NF-kappaB pathway activation, Int. Immunopharmacol., 23, 294, 10.1016/j.intimp.2014.09.005 Da Silva, 2012, Large procyanidins prevent bile-acid-induced oxidant production and membrane-initiated ERK1/2, p38, and Akt activation in Caco-2 cells, Free Radic. Biol. Med., 52, 151, 10.1016/j.freeradbiomed.2011.10.436 Delmastro-Greenwood, 2015, Nitrite and nitrate-dependent generation of anti-inflammatory fatty acid nitroalkenes, Free Radic. Biol. Med., 89, 333, 10.1016/j.freeradbiomed.2015.07.149 Duda-Chodak, 2015, Interaction of dietary compounds, especially polyphenols, with the intestinal microbiota: a review, Eur. J. Nutr., 54, 325, 10.1007/s00394-015-0852-y Dykhuizen, 1996, Antimicrobial effect of acidified nitrite on gut pathogens: importance of dietary nitrate in host defense, Antimicrob. Agents Chemother., 40, 1422, 10.1128/AAC.40.6.1422 Dykhuizen, 1998, Helicobacter pylori is killed by nitrite under acidic conditions, Gut, 42, 334, 10.1136/gut.42.3.334 Eckmann, 2011, NF-kappaB and mucosal homeostasis, Curr. Top. Microbiol. Immunol., 349, 145 Eggler, 2005, Modifying specific cysteines of the electrophile-sensing human Keap1 protein is insufficient to disrupt binding to the Nrf2 domain Neh2, Proc. Natl. Acad. Sci. U. S. A., 102, 10070, 10.1073/pnas.0502402102 Eggler, 2008, Molecular mechanisms of natural products in chemoprevention: induction of cytoprotective enzymes by Nrf2, Mol. Nutr. Food Res., 52, S84 Erlejman, 2004, The interaction of flavonoids with membranes: potential determinant of flavonoid antioxidant effects, Free Radic. Res., 38, 1311, 10.1080/10715760400016105 Erlejman, 2006, Procyanidins protect Caco-2 cells from bile acid- and oxidant-induced damage, Free Radic. Biol. Med., 41, 1247, 10.1016/j.freeradbiomed.2006.07.002 Erlejman, 2008, TNFalpha-induced NF-kappaB activation and cell oxidant production are modulated by hexameric procyanidins in Caco-2 cells, Arch. Biochem. Biophys., 476, 186, 10.1016/j.abb.2008.01.024 Everard, 2013, Diabetes, obesity and gut microbiota. Best practice & research, Clin. Gastroenterol., 27, 73 Farooqui, 2015, Synergistic antimicrobial activity of Camellia sinensis and Juglans regia against multidrug-resistant bacteria, PLoS One, 10, e0118431, 10.1371/journal.pone.0118431 Farzaei, 2015, The role of dietary polyphenols in the management of inflammatory bowel disease, Curr. Pharm. Biotechnol., 16, 196, 10.2174/1389201016666150118131704 Fazzari, 2014, Olives and olive oil are sources of electrophilic fatty acid nitroalkenes, PLoS One, 9, e84884, 10.1371/journal.pone.0084884 Forman, 2001, Signaling by the respiratory burst in macrophages, IUBMB Life, 51, 365, 10.1080/152165401753366122 Fraga, 2011, Dietary flavonoids: role of (−)-epicatechin and related procyanidins in cell signaling, Free Radic. Biol. Med., 51, 813, 10.1016/j.freeradbiomed.2011.06.002 Fraga, 2010, Basic biochemical mechanisms behind the health benefits of polyphenols, Mol. Aspects Med., 31, 435, 10.1016/j.mam.2010.09.006 Fraga, 2007, Plant polyphenols: how to translate their in vitro antioxidant actions to in vivo conditions, IUBMB Life, 59, 308, 10.1080/15216540701230529 Fu, 2014, Cyanidin-3-O-beta-glucoside ameliorates lipopolysaccharide-induced acute lung injury by reducing TLR4 recruitment into lipid rafts, Biochem. Pharmacol., 90, 126, 10.1016/j.bcp.2014.05.004 Fujimura, 2004, Lipid raft-associated catechin suppresses the FcepsilonRI expression by inhibiting phosphorylation of the extracellular signal-regulated kinase1/2, FEBS Lett., 556, 204, 10.1016/S0014-5793(03)01432-7 Gago, 2007, Red wine-dependent reduction of nitrite to nitric oxide in the stomach, Free Radic. Biol. Med., 43, 1233, 10.1016/j.freeradbiomed.2007.06.007 Galleano, 2010, Antioxidant actions of flavonoids: thermodynamic and kinetic analysis, Arch. Biochem. Biophys., 501, 23, 10.1016/j.abb.2010.04.005 Govoni, 2008, The increase in plasma nitrite after a dietary nitrate load is markedly attenuated by an antibacterial mouthwash, Nitric Oxide, 19, 333, 10.1016/j.niox.2008.08.003 Groschwitz, 2009, Intestinal barrier function: molecular regulation and disease pathogenesis, J. Allergy Clin. Immunol., 124, 3, 10.1016/j.jaci.2009.05.038 Hezel, 2015, The oral microbiome and nitric oxide homoeostasis, Oral Dis., 21, 7, 10.1111/odi.12157 Holmes-McNary, 2000, Chemopreventive properties of trans-resveratrol are associated with inhibition of activation of the IkappaB kinase, Cancer Res., 60, 3477 Hsiao, 2013, Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders, Cell, 155, 1451, 10.1016/j.cell.2013.11.024 Hwang, 2011, Anthocyanins from purple sweet potato attenuate dimethylnitrosamine-induced liver injury in rats by inducing Nrf2-mediated antioxidant enzymes and reducing COX-2 and iNOS expression, Food Chem. Toxicol., 49, 93, 10.1016/j.fct.2010.10.002 Hyde, 2014, Metagenomic analysis of nitrate-reducing bacteria in the oral cavity: implications for nitric oxide homeostasis, PLoS One, 9, e88645, 10.1371/journal.pone.0088645 Iles, 2002, Macrophage signaling and respiratory burst, Immunol. Res., 26, 95, 10.1385/IR:26:1-3:095 Jadert, 2012, Decreased leukocyte recruitment by inorganic nitrate and nitrite in microvascular inflammation and NSAID-induced intestinal injury, Free Radic. Biol. Med., 52, 683, 10.1016/j.freeradbiomed.2011.11.018 Jadert, 2014, Preventive and therapeutic effects of nitrite supplementation in experimental inflammatory bowel disease, Redox Biol., 2, 73, 10.1016/j.redox.2013.12.012 Jansson, 2007, Protection from nonsteroidal anti-inflammatory drug (NSAID)-induced gastric ulcers by dietary nitrate, Free Radic. Biol. Med., 42, 510, 10.1016/j.freeradbiomed.2006.11.018 Jobin, 1999, Curcumin blocks cytokine-mediated NF-kappa B activation and proinflammatory gene expression by inhibiting inhibitory factor I-kappa B kinase activity, J. Immunol., 163, 3474, 10.4049/jimmunol.163.6.3474 Jones, 2011, Recognition of bacterial pathogens and mucosal immunity, Cell. Microbiol., 13, 670, 10.1111/j.1462-5822.2011.01579.x Jones, 2012, Reactive oxygen production induced by the gut microbiota: pharmacotherapeutic implications, Curr. Med. Chem., 19, 1519, 10.2174/092986712799828283 Jones, 2006, Redefining oxidative stress, Antioxid. Redox Signal., 8, 1865, 10.1089/ars.2006.8.1865 Jung, 2008, Dynein light chain LC8 negatively regulates NF-kappaB through the redox-dependent interaction with IkappaBalpha, J. Biol. Chem., 283, 23863, 10.1074/jbc.M803072200 Kaliannan, 2015, A host-microbiome interaction mediates the opposing effects of omega-6 and omega-3 fatty acids on metabolic endotoxemia, Sci. Rep., 5, 11276, 10.1038/srep11276 Kang, 2007, Equol inhibits nitric oxide production and inducible nitric oxide synthase gene expression through down-regulating the activation of Akt, Int. Immunopharmacol., 7, 491, 10.1016/j.intimp.2006.12.004 Kim, 2005, The flavonoid luteolin prevents lipopolysaccharide-induced NF-kappaB signalling and gene expression by blocking IkappaB kinase activity in intestinal epithelial cells and bone-marrow derived dendritic cells, Immunology, 115, 375, 10.1111/j.1365-2567.2005.02156.x Kim, 2003, Curcumin suppresses Janus kinase-STAT inflammatory signaling through activation of Src homology 2 domain-containing tyrosine phosphatase 2 in brain microglia, J. Immunol., 171, 6072, 10.4049/jimmunol.171.11.6072 Kim, 2003, Luteolin inhibits the nuclear factor-kappa B transcriptional activity in Rat-1 fibroblasts, Biochem. Pharmacol., 66, 955, 10.1016/S0006-2952(03)00465-9 Kim, 2010, A protective role of nuclear factor-erythroid 2-related factor-2 (Nrf2) in inflammatory disorders, Mutat. Res., 690, 12, 10.1016/j.mrfmmm.2009.09.007 Kong, 2001, Induction of xenobiotic enzymes by the MAP kinase pathway and the antioxidant or electrophile response element (ARE/EpRE), Drug Metab. Rev., 33, 255, 10.1081/DMR-120000652 Krug, 2014, Tight junction, selective permeability, and related diseases, Semin. Cell Dev. Biol., 36, 166, 10.1016/j.semcdb.2014.09.002 Landy, 2016, Tight junctions in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer, World J. Gastroenterol., 22, 3117, 10.3748/wjg.v22.i11.3117 Lawrence, 2009, The nuclear factor NF-kappaB pathway in inflammation, Cold Spring Harb. Perspect. Biol., 1, a001651, 10.1101/cshperspect.a001651 Lee, 2013, Protective effects of (−)-epigallocatechin-3-gallate against TNF-alpha-induced lung inflammation via ROS-dependent ICAM-1 inhibition, J. Nutr. Biochem., 24, 124, 10.1016/j.jnutbio.2012.03.009 Lee, 2008, Bacterial-modulated signaling pathways in gut homeostasis, Sci. Signal., 1, pe24, 10.1126/stke.121pe24 Lee, 2015, Intestinal permeability regulation by tight junction: implication on inflammatory bowel diseases, Intest. Res., 13, 11, 10.5217/ir.2015.13.1.11 Lee-Hilz, 2006, Pro-oxidant activity of flavonoids induces EpRE-mediated gene expression, Chem. Res. Toxicol., 19, 1499, 10.1021/tx060157q Li, 2008, Activation of Nrf2-antioxidant signaling attenuates NFkappaB-inflammatory response and elicits apoptosis, Biochem. Pharmacol., 76, 1485, 10.1016/j.bcp.2008.07.017 Lundberg, 2013, Biology of nitrogen oxides in the gastrointestinal tract, Gut, 62, 616, 10.1136/gutjnl-2011-301649 Lundberg, 1994, Intragastric nitric oxide production in humans: measurements in expelled air, Gut, 35, 1543, 10.1136/gut.35.11.1543 Lundberg, 2004, Nitrate, bacteria and human health, Nat. Rev. Microbiol., 2, 593, 10.1038/nrmicro929 Lundberg, 2008, The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics, Nat. Rev. Drug Discov., 7, 156, 10.1038/nrd2466 Ma, 2004, TNF-alpha-induced increase in intestinal epithelial tight junction permeability requires NF-kappa B activation, Am. J. Physiol. Gastrointest. Liver Physiol., 286, G367, 10.1152/ajpgi.00173.2003 Ma, 2005, Mechanism of TNF-{alpha} modulation of Caco-2 intestinal epithelial tight junction barrier: role of myosin light-chain kinase protein expression, Am. J. Physiol. Gastrointest. Liver Physiol., 288, G422, 10.1152/ajpgi.00412.2004 Mackenzie, 2009, Dimeric procyanidins are inhibitors of NF-kappaB-DNA binding, Biochem. Pharmacol., 78, 1252, 10.1016/j.bcp.2009.06.111 Martin, 2004, Regulation of heme oxygenase-1 expression through the phosphatidylinositol 3-kinase/Akt pathway and the Nrf2 transcription factor in response to the antioxidant phytochemical carnosol, J. Biol. Chem., 279, 8919, 10.1074/jbc.M309660200 Mazidi, 2016, Gut microbiome and metabolic syndrome, Diabetes Metab. Syndr., 10, S150, 10.1016/j.dsx.2016.01.024 Metodiewa, 1999, Quercetin may act as a cytotoxic prooxidant after its metabolic activation to semiquinone and quinoidal product, Free Radic. Biol. Med., 26, 107, 10.1016/S0891-5849(98)00167-1 Minihane, 2015, Low-grade inflammation, diet composition and health: current research evidence and its translation, Br. J. Nutr., 114, 999, 10.1017/S0007114515002093 Mo, 2012, Nitrite activates AMP kinase to stimulate mitochondrial biogenesis independent of soluble guanylate cyclase, Free Radic. Biol. Med., 53, 1440, 10.1016/j.freeradbiomed.2012.07.080 Montenegro, 2012, Antihypertensive and antioxidant effects of a single daily dose of sodium nitrite in a model of renovascular hypertension, Naunyn-Schmiedeberg’s Arch. Pharmacol., 385, 509, 10.1007/s00210-011-0712-0 Na, 2008, (−)-Epigallocatechin gallate induces Nrf2-mediated antioxidant enzyme expression via activation of PI3K and ERK in human mammary epithelial cells, Arch. Biochem. Biophys., 476, 171, 10.1016/j.abb.2008.04.003 Nam, 2001, Ester bond-containing tea polyphenols potently inhibit proteasome activity in vitro and in vivo, J. Biol. Chem., 276, 13322, 10.1074/jbc.M004209200 Neish, 2000, Prokaryotic regulation of epithelial responses by inhibition of IkappaB-alpha ubiquitination, Science, 289, 1560, 10.1126/science.289.5484.1560 Nunes, 2013, Intestinal anti-inflammatory activity of red wine extract: unveiling the mechanisms in colonic epithelial cells, Food Funct., 4, 373, 10.1039/C2FO30233K Nunes, 2016, Red wine polyphenol extract efficiently protects intestinal epithelial cells from inflammation via opposite modulation of JAK/STAT and Nrf2 pathways, Toxicol. Res., 5, 53, 10.1039/C5TX00214A Ollila, 2002, Characterization of flavonoid–biomembrane interactions, Arch. Biochem. Biophys., 399, 13, 10.1006/abbi.2001.2759 Omar, 2016, Therapeutic effects of inorganic nitrate and nitrite in cardiovascular and metabolic diseases, J. Intern. Med., 279, 315, 10.1111/joim.12441 Pan, 2000, Suppression of lipopolysaccharide-induced nuclear factor-kappaB activity by theaflavin-3,3'-digallate from black tea and other polyphenols through down-regulation of IkappaB kinase activity in macrophages, Biochem. Pharmacol., 59, 357, 10.1016/S0006-2952(99)00335-4 Parkar, 2013, Fecal microbial metabolism of polyphenols and its effects on human gut microbiota, Anaerobe, 23, 12, 10.1016/j.anaerobe.2013.07.009 Patel, 2008, Polymeric black tea polyphenols induce phase II enzymes via Nrf2 in mouse liver and lungs, Free Radic. Biol. Med., 44, 1897, 10.1016/j.freeradbiomed.2008.02.006 Peri, 2005, Apples increase nitric oxide production by human saliva at the acidic pH of the stomach: a new biological function for polyphenols with a catechol group?, Free Radic. Biol. Med., 39, 668, 10.1016/j.freeradbiomed.2005.04.021 Petersson, 2007, Dietary nitrate increases gastric mucosal blood flow and mucosal defense, Am. J. Physiol. Gastrointest. Liver Physiol., 292, G718, 10.1152/ajpgi.00435.2006 Queipo-Ortuno, 2012, Influence of red wine polyphenols and ethanol on the gut microbiota ecology and biochemical biomarkers, Am. J. Clin. Nutr., 95, 1323, 10.3945/ajcn.111.027847 Rahman, 2006, Regulation of inflammation and redox signaling by dietary polyphenols, Biochem. Pharmacol., 72, 1439, 10.1016/j.bcp.2006.07.004 Rakoff-Nahoum, 2004, Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis, Cell, 118, 229, 10.1016/j.cell.2004.07.002 Rao, 2002, Tyrosine phosphorylation and dissociation of occludin-ZO-1 and E-cadherin-beta-catenin complexes from the cytoskeleton by oxidative stress, Biochem. J, 368, 471, 10.1042/bj20011804 Reinders, 2007, Rectal nitric oxide and fecal calprotectin in inflammatory bowel disease, Scand. J. Gastroenterol., 42, 1151, 10.1080/00365520701320505 Ren, 2015, The anti-inflammatory effect and potential mechanism of cardamonin in DSS-induced colitis, Am. J. Physiol. Gastrointest. Liver Physiol., 309, G517, 10.1152/ajpgi.00133.2015 Rhee, 2005, Intracellular messenger function of hydrogen peroxide and its regulation by peroxiredoxins, Curr. Opin. Cell Biol., 17, 183, 10.1016/j.ceb.2005.02.004 Ripley, 2010, Green tea polyphenol epigallocatechin gallate inhibits cell signaling by inducing SOCS1 gene expression, Int. Immunol., 22, 359, 10.1093/intimm/dxq015 Rocha, 2009, Dietary polyphenols generate nitric oxide from nitrite in the stomach and induce smooth muscle relaxation, Toxicology, 265, 41, 10.1016/j.tox.2009.09.008 Rocha, 2011, Dietary nitrite in nitric oxide biology: a redox interplay with implications for pathophysiology and therapeutics, Curr. Drug Targets, 12, 1351, 10.2174/138945011796150334 Rocha, 2012, Intragastric nitration by dietary nitrite: implications for modulation of protein and lipid signaling, Free Radic. Biol. Med., 52, 693, 10.1016/j.freeradbiomed.2011.11.011 Rocha, 2014, A shortcut to wide-ranging biological actions of dietary polyphenols: modulation of the nitrate-nitrite-nitric oxide pathway in the gut, Food Funct., 5, 1646, 10.1039/C4FO00124A Rocha, 2016, Role of nitrite, urate and pepsin in the gastroprotective effects of saliva, Redox Biol., 8, 407, 10.1016/j.redox.2016.04.002 Romier, 2009, Dietary polyphenols can modulate the intestinal inflammatory response, Nutr. Rev., 67, 363, 10.1111/j.1753-4887.2009.00210.x Scarabelli, 2009, Targeting STAT1 by myricetin and delphinidin provides efficient protection of the heart from ischemia/reperfusion-induced injury, FEBS Lett., 583, 531, 10.1016/j.febslet.2008.12.037 Scheperjans, 2015, Gut microbiota are related to Parkinson's disease and clinical phenotype, Mov. Disord., 30, 350, 10.1002/mds.26069 Sekirov, 2010, Gut microbiota in health and disease, Physiol. Rev., 90, 859, 10.1152/physrev.00045.2009 Selma, 2009, Interaction between phenolics and gut microbiota: role in human health, J. Agric. Food Chem., 57, 6485, 10.1021/jf902107d Serra, 2013, Cyanidin-3-glucoside suppresses cytokine-induced inflammatory response in human intestinal cells: comparison with 5-aminosalicylic acid, PLoS One, 8, e73001, 10.1371/journal.pone.0073001 Serra, 2014, Resveratrol modulates cytokine-induced Jak/STAT activation more efficiently than 5-aminosalicylic acid: an in vitro approach, PLoS One, 9, e109048, 10.1371/journal.pone.0109048 Shahpiri, 2016, Phytochemicals as future drugs for Parkinson's disease: a comprehensive review, Rev. Neurosci., 27, 651, 10.1515/revneuro-2016-0004 Sheth, 2003, Role of phosphatidylinositol 3-kinase in oxidative stress-induced disruption of tight junctions, J. Biol. Chem., 278, 49239, 10.1074/jbc.M305654200 Shifflett, 2005, Enteropathogenic E. coli disrupts tight junction barrier function and structure in vivo, Lab. Invest., 85, 1308, 10.1038/labinvest.3700330 Simonovic, 2000, Enteropathogenic Escherichia coli dephosphorylates and dissociates occludin from intestinal epithelial tight junctions, Cell. Microbiol., 2, 305, 10.1046/j.1462-5822.2000.00055.x Sindler, 2011, Nitrite supplementation reverses vascular endothelial dysfunction and large elastic artery stiffness with aging, Aging cell, 10, 429, 10.1111/j.1474-9726.2011.00679.x Sindler, 2014, Inorganic nitrite supplementation for healthy arterial aging, J. Appl. Physiol., 116, 463, 10.1152/japplphysiol.01100.2013 Sirota, 2015, The role of the catecholic and the electrophilic moieties of caffeic acid in Nrf2/Keap1 pathway activation in ovarian carcinoma cell lines, Redox Biol., 4, 48, 10.1016/j.redox.2014.11.012 Smecuol, 1997, Gastrointestinal permeability in celiac disease, Gastroenterology, 112, 1129, 10.1016/S0016-5085(97)70123-9 Son, 2010, Piceatannol, a catechol-type polyphenol, inhibits phorbol ester-induced NF-{kappa}B activation and cyclooxygenase-2 expression in human breast epithelial cells: cysteine 179 of IKK{beta} as a potential target, Carcinogenesis, 31, 1442, 10.1093/carcin/bgq099 Sonoda, 1999, Clostridium perfringens enterotoxin fragment removes specific claudins from tight junction strands: evidence for direct involvement of claudins in tight junction barrier, J. Cell Biol., 147, 195, 10.1083/jcb.147.1.195 Steffen, 2007, (−)-Epicatechin elevates nitric oxide in endothelial cells via inhibition of NADPH oxidase, Biochem. Biophys. Res. Commun., 359, 828, 10.1016/j.bbrc.2007.05.200 Steffen, 2008, Mono-O-methylated flavanols and other flavonoids as inhibitors of endothelial NADPH oxidase, Arch. Biochem. Biophys., 469, 209, 10.1016/j.abb.2007.10.012 Stokes, 2009, Dietary nitrite prevents hypercholesterolemic microvascular inflammation and reverses endothelial dysfunction, Am. J. Physiol. Heart Circ. Physiol., 296, H1281, 10.1152/ajpheart.01291.2008 Surh, 2008, Nrf2 as a master redox switch in turning on the cellular signaling involved in the induction of cytoprotective genes by some chemopreventive phytochemicals, Planta Med., 74, 1526, 10.1055/s-0028-1088302 Surh, 2009, Role of Nrf2-mediated heme oxygenase-1 upregulation in adaptive survival response to nitrosative stress, Arch. Pharm. Res., 32, 1163, 10.1007/s12272-009-1807-8 Suzuki, 2009, Quercetin enhances intestinal barrier function through the assembly of zonula [corrected] occludens-2, occludin, and claudin-1 and the expression of claudin-4 in Caco-2 cells, J. Nutr., 139, 965, 10.3945/jn.108.100867 Suzuki, 2011, Role of flavonoids in intestinal tight junction regulation, J. Nutr. Biochem., 22, 401, 10.1016/j.jnutbio.2010.08.001 Suzuki, 2011, Kaempferol enhances intestinal barrier function through the cytoskeletal association and expression of tight junction proteins in Caco-2 cells, J. Nutr., 141, 87, 10.3945/jn.110.125633 Suzuki, 2013, Regulation of intestinal epithelial permeability by tight junctions, Cell. Mol. Life Sci., 70, 631, 10.1007/s00018-012-1070-x Tachibana, 2004, Tea polyphenol epigallocatechin-3-gallate associates with plasma membrane lipid rafts: lipid rafts mediate anti-allergic action of the catechin, Biofactors, 21, 383, 10.1002/biof.552210174 Tangney, 2013, Polyphenols, inflammation, and cardiovascular disease, Curr. Atheroscler. Rep., 15, 324, 10.1007/s11883-013-0324-x Turnbaugh, 2006, An obesity-associated gut microbiome with increased capacity for energy harvest, Nature, 444, 1027, 10.1038/nature05414 Turnbaugh, 2007, The human microbiome project, Nature, 449, 804, 10.1038/nature06244 Ukil, 2006, Protection from experimental colitis by theaflavin-3,3'-digallate correlates with inhibition of IKK and NF-kappaB activation, Br. J. Pharmacol., 149, 121, 10.1038/sj.bjp.0706847 Valdes, 2015, The relationship between phenolic compounds from diet and microbiota: impact on human health, Food Funct., 6, 2424, 10.1039/C5FO00322A Verstraeten, 2013, Procyanidins can interact with Caco-2 cell membrane lipid rafts: involvement of cholesterol, Biochim. Biophys. Acta, 1828, 2646, 10.1016/j.bbamem.2013.07.023 Visser, 2009, Tight junctions, intestinal permeability, and autoimmunity: celiac disease and type 1 diabetes paradigms, Ann. N. Y. Acad. Sci., 1165, 195, 10.1111/j.1749-6632.2009.04037.x Wakabayashi, 2010, When NRF2 talks, who's listening?, Antioxid. Redox Signal., 13, 1649, 10.1089/ars.2010.3216 Wallace, 2000, Nitric oxide in mucosal defense: a little goes a long way, Gastroenterology, 119, 512, 10.1053/gast.2000.9304 Wallace, 2008, Prostaglandins, NSAIDs, and gastric mucosal protection: why doesn't the stomach digest itself?, Physiol. Rev., 88, 1547, 10.1152/physrev.00004.2008 Wentworth, 2010, Commensal-epithelial signaling mediated via formyl peptide receptors, Am. J. Pathol., 177, 2782, 10.2353/ajpath.2010.100529 Wu, 2006, Upregulation of heme oxygenase-1 by epigallocatechin-3-gallate via the phosphatidylinositol 3-kinase/Akt and ERK pathways, Life Sci., 78, 2889, 10.1016/j.lfs.2005.11.013 Yang, 2001, The green tea polyphenol (−)-epigallocatechin-3-gallate blocks nuclear factor-kappa B activation by inhibiting I kappa B kinase activity in the intestinal epithelial cell line IEC-6, Mol. Pharmacol., 60, 528 Ye, 2006, Molecular mechanism of tumor necrosis factor-alpha modulation of intestinal epithelial tight junction barrier, Am. J. Physiol. Gastrointest. Liver Physiol., 290, G496, 10.1152/ajpgi.00318.2005 Yokoyama, 2008, Isolation and characterization of a novel equol-producing bacterium from human feces, Biosci. Biotechnol. Biochem., 72, 2660, 10.1271/bbb.80329 de Kort, 2011, Leaky gut and diabetes mellitus: what is the link?, Obes. Rev., 12, 449, 10.1111/j.1467-789X.2010.00845.x