Indole-3-Aldehyde Reduces Inflammatory Responses and Restores Intestinal Epithelial Barrier Function Partially via Aryl Hydrocarbon Receptor (AhR) in Experimental Colitis Models

References

• Chang JT. Pathophysiology of Inflammatory Bowel Diseases. N Engl J Med. 2021;384(14):1378. doi:10.1056/NEJMc2101562
   PubMed Web of Science ®Google Scholar
• Neurath MF. Current and emerging therapeutic targets for IBD. Nat Rev Gastroenterol Hepatol. 2017;14(5):269–278. doi:10.1038/nrgastro.2016.208
   PubMed Web of Science ®Google Scholar
• Li W, Hang S, Fang Y, et al. A bacterial bile acid metabolite modulates T(reg) activity through the nuclear hormone receptor NR4A1. Cell Host Microbe. 2021;29(9):1366–1377 e9. doi:10.1016/j.chom.2021.07.013
   PubMed Web of Science ®Google Scholar
• Lavelle A, Sokol H. Gut microbiota-derived metabolites as key actors in inflammatory bowel disease. Nat Rev Gastroenterol Hepatol. 2020;17(4):223–237. doi:10.1038/s41575-019-0258-z
   PubMed Web of Science ®Google Scholar
• Roager HM, Licht TR. Microbial tryptophan catabolites in health and disease. Nat Commun. 2018;9(1):3294. doi:10.1038/s41467-018-05470-4
   PubMedGoogle Scholar
• Gutierrez-Vazquez C, Quintana FJ. Regulation of the Immune Response by the Aryl Hydrocarbon Receptor. Immunity. 2018;48(1):19–33. doi:10.1016/j.immuni.2017.12.012
   PubMed Web of Science ®Google Scholar
• Nikolaus S, Schulte B, Al-Massad N, et al. Increased Tryptophan Metabolism Is Associated With Activity of Inflammatory Bowel Diseases. Gastroenterology. 2017;153(6):1504–1516 e2. doi:10.1053/j.gastro.2017.08.028
   PubMed Web of Science ®Google Scholar
• Lamas B, Richard ML, Leducq V, et al. CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. Nat Med. 2016;22(6):598–605. doi:10.1038/nm.4102
   PubMed Web of Science ®Google Scholar
• Alexeev EE, Lanis JM, Kao DJ, et al. Microbiota-Derived Indole Metabolites Promote Human and Murine Intestinal Homeostasis through Regulation of Interleukin-10 Receptor. Am J Pathol. 2018;188(5):1183–1194. doi:10.1016/j.ajpath.2018.01.011
   PubMed Web of Science ®Google Scholar
• Islam J, Sato S, Watanabe K, et al. Dietary tryptophan alleviates dextran sodium sulfate-induced colitis through aryl hydrocarbon receptor in mice. J Nutr Biochem. 2017;42:43–50. doi:10.1016/j.jnutbio.2016.12.019
   PubMed Web of Science ®Google Scholar
• Ala M. Tryptophan metabolites modulate inflammatory bowel disease and colorectal cancer by affecting immune system. Int Rev Immunol. 2022;41(3):326–345. doi:10.1080/08830185.2021.1954638
   PubMed Web of Science ®Google Scholar
• Zhao C, Bao L, Qiu M, et al. Dietary Tryptophan-Mediated Aryl Hydrocarbon Receptor Activation by the Gut Microbiota Alleviates Escherichia coli-Induced Endometritis in Mice. Microbiol Spectr. 2022;10(4):e0081122. doi:10.1128/spectrum.00811-22
   PubMed Web of Science ®Google Scholar
• Kewley RJ, Whitelaw ML, Chapman-Smith A. The mammalian basic helix-loop-helix/PAS family of transcriptional regulators. Int J Biochem Cell Biol. 2004;36(2):189–204. doi:10.1016/s1357-2725(03)00211-5
   PubMed Web of Science ®Google Scholar
• Larigot L, Juricek L, Dairou J, Coumoul X. AhR signaling pathways and regulatory functions. Biochim Open. 2018;7:1–9. doi:10.1016/j.biopen.2018.05.001
   PubMedGoogle Scholar
• Ishihara Y, Kado SY, Bein KJ, et al. Aryl Hydrocarbon Receptor Signaling Synergizes with TLR/NF-kappaB-Signaling for Induction of IL-22 Through Canonical and Non-Canonical AhR Pathways. Front Toxicol. 2021;3:787360. doi:10.3389/ftox.2021.787360
   PubMedGoogle Scholar
• Monteleone I, Rizzo A, Sarra M, et al. Aryl hydrocarbon receptor-induced signals up-regulate IL-22 production and inhibit inflammation in the gastrointestinal tract. Gastroenterology. 2011;141(1):237–48, 248 e1. doi:10.1053/j.gastro.2011.04.007
   PubMed Web of Science ®Google Scholar
• Alvik K, Shao P, Hutin D, Baglole C, Grant DM, Matthews J. Increased sensitivity to chemically induced colitis in mice harboring a DNA-binding deficient aryl hydrocarbon receptor. Toxicol Sci. 2023;191(2):321–331. doi:10.1093/toxsci/kfac132
   PubMed Web of Science ®Google Scholar
• Lamas B, Natividad JM, Sokol H. Aryl hydrocarbon receptor and intestinal immunity. Mucosal Immunol. 2018;11(4):1024–1038. doi:10.1038/s41385-018-0019-2
   PubMed Web of Science ®Google Scholar
• Cervantes-Barragan L, Chai JN, Tianero MD, et al. Lactobacillus reuteri induces gut intraepithelial CD4(+)CD8alphaalpha(+) T cells. Science. 2017;357(6353):806–810. doi:10.1126/science.aah5825
   PubMed Web of Science ®Google Scholar
• Hou Q, Ye L, Liu H, et al. Lactobacillus accelerates ISCs regeneration to protect the integrity of intestinal mucosa through activation of STAT3 signaling pathway induced by LPLs secretion of IL-22. Cell Death Differ. 2018;25(9):1657–1670. doi:10.1038/s41418-018-0070-2
   PubMed Web of Science ®Google Scholar
• Scott SA, Fu J, Chang PV. Microbial tryptophan metabolites regulate gut barrier function via the aryl hydrocarbon receptor. Proc Natl Acad Sci U S A. 2020;117(32):19376–19387. doi:10.1073/pnas.2000047117
   PubMed Web of Science ®Google Scholar
• Zelante T, Iannitti RG, Cunha C, et al. Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity. 2013;39(2):372–385. doi:10.1016/j.immuni.2013.08.003
   PubMed Web of Science ®Google Scholar
• Wilck N, Matus MG, Kearney SM, et al. Salt-responsive gut commensal modulates T(H)17 axis and disease. Nature. 2017;551(7682):585–589. doi:10.1038/nature24628
   PubMed Web of Science ®Google Scholar
• Waetzig GH, Seegert D, Rosenstiel P, Nikolaus S, Schreiber S. p38 mitogen-activated protein kinase is activated and linked to TNF-alpha signaling in inflammatory bowel disease. J Immunol. 2002;168(10):5342–5351. doi:10.4049/jimmunol.168.10.5342
   PubMed Web of Science ®Google Scholar
• Dahan S, Roda G, Pinn D, et al. Epithelial: lamina propria lymphocyte interactions promote epithelial cell differentiation. Gastroenterology. 2008;134(1):192–203. doi:10.1053/j.gastro.2007.10.022
   PubMed Web of Science ®Google Scholar
• Mandic AD, Bennek E, Verdier J, et al. c-Jun N-terminal kinase 2 promotes enterocyte survival and goblet cell differentiation in the inflamed intestine. Mucosal Immunol. 2017;10(5):1211–1223. doi:10.1038/mi.2016.125
   PubMed Web of Science ®Google Scholar
• Atreya I, Atreya R, Neurath MF. NF-kappaB in inflammatory bowel disease. J Intern Med. 2008;263(6):591–596. doi:10.1111/j.1365-2796.2008.01953.x
   PubMed Web of Science ®Google Scholar
• Andresen L, Jorgensen VL, Perner A, Hansen A, Eugen-Olsen J, Rask-Madsen J. Activation of nuclear factor kappaB in colonic mucosa from patients with collagenous and ulcerative colitis. Gut. 2005;54(4):503–509. doi:10.1136/gut.2003.034165
   PubMed Web of Science ®Google Scholar
• Na YR, Stakenborg M, Seok SH, Matteoli G. Macrophages in intestinal inflammation and resolution: a potential therapeutic target in IBD. Nat Rev Gastroenterol Hepatol. 2019;16(9):531–543. doi:10.1038/s41575-019-0172-4
   PubMed Web of Science ®Google Scholar
• Murano M, Maemura K, Hirata I, et al. Therapeutic effect of intracolonically administered nuclear factor kappa B (p65) antisense oligonucleotide on mouse dextran sulphate sodium (DSS)-induced colitis. Clin Exp Immunol. 2000;120(1):51–58. doi:10.1046/j.1365-2249.2000.01183.x
   PubMed Web of Science ®Google Scholar
• Wirtz S, Neufert C, Weigmann B, Neurath MF. Chemically induced mouse models of intestinal inflammation. Nat Protoc. 2007;2(3):541–546. doi:10.1038/nprot.2007.41
   PubMed Web of Science ®Google Scholar
• Mullish BH, Pechlivanis A, Barker GF, Thursz MR, Marchesi JR, McDonald JAK. Functional microbiomics: evaluation of gut microbiota-bile acid metabolism interactions in health and disease. Methods. 2018;149:49–58. doi:10.1016/j.ymeth.2018.04.028
   PubMed Web of Science ®Google Scholar
• Segata N, Izard J, Waldron L, et al. Metagenomic biomarker discovery and explanation. Genome Biol. 2011;12(6):R60. doi:10.1186/gb-2011-12-6-r60
   PubMed Web of Science ®Google Scholar
• Cai L, Qin X, Xu Z, et al. Comparison of Cytotoxicity Evaluation of Anticancer Drugs between Real-Time Cell Analysis and CCK-8 Method. ACS Omega. 2019;4(7):12036–12042. doi:10.1021/acsomega.9b01142
   PubMed Web of Science ®Google Scholar
• Gupta V, Doshi N, Mitragotri S. Permeation of insulin, calcitonin and exenatide across Caco-2 monolayers: measurement using a rapid, 3-day system. PLoS One. 2013;8(2):e57136. doi:10.1371/journal.pone.0057136
   PubMed Web of Science ®Google Scholar
• Sanders SE, Madara JL, McGuirk DK, Gelman DS, Colgan SP. Assessment of inflammatory events in epithelial permeability: a rapid screening method using fluorescein dextrans. Epithelial Cell Biol. 1995;4(1):25–34.
   PubMedGoogle Scholar
• Ghosh SS, Wang J, Yannie PJ, Ghosh S. Intestinal Barrier Dysfunction, LPS Translocation, and Disease Development. J Endocr Soc. 2020;4(2):bvz039. doi:10.1210/jendso/bvz039
   PubMed Web of Science ®Google Scholar
• Su L, Nalle SC, Shen L, et al. TNFR2 activates MLCK-dependent tight junction dysregulation to cause apoptosis-mediated barrier loss and experimental colitis. Gastroenterology. 2013;145(2):407–415. doi:10.1053/j.gastro.2013.04.011
   PubMed Web of Science ®Google Scholar
• Turner JR, Rill BK, Carlson SL, et al. Physiological regulation of epithelial tight junctions is associated with myosin light-chain phosphorylation. Am J Physiol. 1997;273(4):C1378–85. doi:10.1152/ajpcell.1997.273.4.C1378
   PubMed Web of Science ®Google Scholar
• Nighot M, Rawat M, Al-Sadi R, Castillo EF, Nighot P, Ma TY. Lipopolysaccharide-Induced Increase in Intestinal Permeability Is Mediated by TAK-1 Activation of IKK and MLCK/MYLK Gene. Am J Pathol. 2019;189(4):797–812. doi:10.1016/j.ajpath.2018.12.016
   PubMed Web of Science ®Google Scholar
• Selvakumar D, Evans D, Coyte KZ, et al. Understanding the development and function of the gut microbiota in health and inflammation. Frontline Gastroenterol. 2022;13(e1):e13–e21. doi:10.1136/flgastro-2022-102119
   PubMed Web of Science ®Google Scholar
• Rothhammer V, Mascanfroni ID, Bunse L, et al. Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor. Nat Med. 2016;22(6):586–597. doi:10.1038/nm.4106
   PubMed Web of Science ®Google Scholar
• Yu J, Luo Y, Zhu Z, et al. A tryptophan metabolite of the skin microbiota attenuates inflammation in patients with atopic dermatitis through the aryl hydrocarbon receptor. J Allergy Clin Immunol. 2019;143(6):2108–2119 e12. doi:10.1016/j.jaci.2018.11.036
   PubMed Web of Science ®Google Scholar
• Reinecker HC, Steffen M, Witthoeft T, et al. Enhanced secretion of tumour necrosis factor-alpha, IL-6, and IL-1 beta by isolated lamina propria mononuclear cells from patients with ulcerative colitis and Crohn’s disease. Clin Exp Immunol. 1993;94(1):174–181. doi:10.1111/j.1365-2249.1993.tb05997.x
   PubMed Web of Science ®Google Scholar
• Ishiguro Y. Mucosal proinflammatory cytokine production correlates with endoscopic activity of ulcerative colitis. J Gastroenterol. 1999;34(1):66–74. doi:10.1007/s005350050218
   PubMed Web of Science ®Google Scholar
• Kai Y, Takahashi I, Ishikawa H, et al. Colitis in mice lacking the common cytokine receptor gamma chain is mediated by IL-6-producing CD4+ T cells. Gastroenterology. 2005;128(4):922–934. doi:10.1053/j.gastro.2005.01.013
   PubMed Web of Science ®Google Scholar
• Schreiber S, Aden K, Bernardes JP, et al. Therapeutic Interleukin-6 Trans-signaling Inhibition by Olamkicept (sgp130Fc) in Patients With Active Inflammatory Bowel Disease. Gastroenterology. 2021;160(7):2354–2366 e11. doi:10.1053/j.gastro.2021.02.062
   PubMed Web of Science ®Google Scholar
• Friedrich M, Pohin M, Powrie F. Cytokine Networks in the Pathophysiology of Inflammatory Bowel Disease. Immunity. 2019;50(4):992–1006. doi:10.1016/j.immuni.2019.03.017
   PubMed Web of Science ®Google Scholar
• Kimura A, Naka T, Nakahama T, et al. Aryl hydrocarbon receptor in combination with Stat1 regulates LPS-induced inflammatory responses. J Exp Med. 2009;206(9):2027–2035. doi:10.1084/jem.20090560
   PubMed Web of Science ®Google Scholar
• Langan D, Perkins DJ, Vogel SN, Moudgil KD. Microbiota-Derived Metabolites, Indole-3-aldehyde and Indole-3-acetic Acid, Differentially Modulate Innate Cytokines and Stromal Remodeling Processes Associated with Autoimmune Arthritis. Int J Mol Sci. 2021;22(4). doi:10.3390/ijms22042017
   PubMed Web of Science ®Google Scholar
• Ovrevik J, Lag M, Lecureur V, et al. AhR and Arnt differentially regulate NF-kappaB signaling and chemokine responses in human bronchial epithelial cells. Cell Commun Signal. 2014;12:48. doi:10.1186/s12964-014-0048-8
   PubMed Web of Science ®Google Scholar
• Vogel CF, Khan EM, Leung PS, et al. Cross-talk between aryl hydrocarbon receptor and the inflammatory response: a role for nuclear factor-kappaB. J Biol Chem. 2014;289(3):1866–1875. doi:10.1074/jbc.M113.505578
   PubMed Web of Science ®Google Scholar
• Diry M, Tomkiewicz C, Koehle C, et al. Activation of the dioxin/aryl hydrocarbon receptor (AhR) modulates cell plasticity through a JNK-dependent mechanism. Oncogene. 2006;25(40):5570–5574. doi:10.1038/sj.onc.1209553
   PubMed Web of Science ®Google Scholar
• Wang Y, Sun D, Song F, Hu Y, Smith DE, Jiang H. Expression and regulation of the proton-coupled oligopeptide transporter PhT2 by LPS in macrophages and mouse spleen. Mol Pharm. 2014;11(6):1880–1888. doi:10.1021/mp500014r
   PubMedGoogle Scholar
• Shin GT, Lee HJ, Kim H. GADD45gamma regulates TNF-alpha and IL-6 synthesis in THP-1 cells. Inflamm Res. 2012;61(11):1195–1202. doi:10.1007/s00011-012-0515-x
   PubMed Web of Science ®Google Scholar
• Zhang W, Shen X, Xie L, Chu M, Ma Y. MicroRNA-181b regulates endotoxin tolerance by targeting IL-6 in macrophage RAW264.7 cells. J Inflamm. 2015;12:18. doi:10.1186/s12950-015-0061-8
   Google Scholar
• Ma P, Liu H-T, Wei P, et al. Chitosan oligosaccharides inhibit LPS-induced over-expression of IL-6 and TNF-α in RAW264. 7 macrophage cells through blockade of mitogen-activated protein kinase (MAPK) and PI3K/Akt signaling pathways. Carbohydr. Polym. 2011;84(4):1391–1398. doi:10.1016/j.carbpol.2011.01.045
   Web of Science ®Google Scholar
• Cho H, Kim E, Lee H, et al. BJ-1108, a 6-Amino-2, 4, 5-trimethylpyridin-3-ol analogue, ameliorates DSS-induced colitis in mice. J Crohns Colitis. 2018;12. doi:10.1093/ecco-jcc/jjx180.224
   PubMed Web of Science ®Google Scholar
• Yu M, Wang Q, Ma Y, et al. Aryl Hydrocarbon Receptor Activation Modulates Intestinal Epithelial Barrier Function by Maintaining Tight Junction Integrity. Int J Biol Sci. 2018;14(1):69–77. doi:10.7150/ijbs.22259
   PubMed Web of Science ®Google Scholar
• Han B, Sheng B, Zhang Z, et al. Aryl Hydrocarbon Receptor Activation in Intestinal Obstruction Ameliorates Intestinal Barrier Dysfunction Via Suppression of MLCK-MLC Phosphorylation Pathway. Shock. 2016;46(3):319–328. doi:10.1097/SHK.0000000000000594
   PubMed Web of Science ®Google Scholar
• Ma TY, Boivin MA, Ye D, Pedram A, Said HM. 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. 2005;288(3):G422–30. doi:10.1152/ajpgi.00412.2004
   PubMed Web of Science ®Google Scholar
• Dong F, Hao F, Murray IA, et al. Intestinal microbiota-derived tryptophan metabolites are predictive of Ah receptor activity. Gut Microbes. 2020;12(1):1–24. doi:10.1080/19490976.2020.1788899
   PubMed Web of Science ®Google Scholar
• Shin NR, Lee JC, Lee HY, et al. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut. 2014;63(5):727–735. doi:10.1136/gutjnl-2012-303839
   PubMed Web of Science ®Google Scholar
• Roopchand DE, Carmody RN, Kuhn P, et al. Dietary Polyphenols Promote Growth of the Gut Bacterium Akkermansia muciniphila and Attenuate High-Fat Diet-Induced Metabolic Syndrome. Diabetes. 2015;64(8):2847–2858. doi:10.2337/db14-1916
   PubMed Web of Science ®Google Scholar
• Yin J, Song Y, Hu Y, et al. Dose-Dependent Beneficial Effects of Tryptophan and Its Derived Metabolites on Akkermansia In Vitro: a Preliminary Prospective Study. Microorganisms. 2021;9(7). doi:10.3390/microorganisms9071511
   Web of Science ®Google Scholar