Butyrate acts through HDAC inhibition to enhance aryl hydrocarbon receptor activation by gut microbiota-derived ligands

References

• Atarashi K, Tanoue T, Shima T, Imaoka A, Kuwahara T, Momose Y, Cheng G, Yamasaki S, Saito T, Ohba Y, et al. Induction of colonic regulatory T cells by indigenous clostridium species. Science. 2011;331(6015):337–15. doi:10.1126/science.1198469
   PubMed Web of Science ®Google Scholar
• Reigstad CS, Salmonson CE, Rainey JF, Szurszewski JH, Linden DR, Sonnenburg JL, Farrugia G, Kashyap PC. Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells. FASEB J. 2015;29(4):1395–1403. doi:10.1096/fj.14-259598
   PubMed Web of Science ®Google Scholar
• Sayin SI, Wahlström A, Felin J, Jäntti S, Marschall H-U, Bamberg K, Angelin B, Hyötyläinen T, Orešič M, Bäckhed F. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metabol. 2013;17(2):225–235. doi:10.1016/j.cmet.2013.01.003
   PubMed Web of Science ®Google Scholar
• Yano JM, Yu K, Donaldson GP, Shastri GG, Ann P, Ma L, Nagler CR, Ismagilov RF, Mazmanian SK, Hsiao EY. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. 2015;161(2):264–276. doi:10.1016/j.cell.2015.02.047
   PubMed Web of Science ®Google Scholar
• Martin-Gallausiaux C, Larraufie P, Jarry A, Béguet-Crespel F, Marinelli L, Ledue F, Reimann F, Blottière HM, Lapaque N. Butyrate produced by commensal bacteria down-regulates indolamine 2,3-dioxygenase 1 (IDO-1) expression via a dual mechanism in human intestinal epithelial cells. Front Immunol. 2018;9:2838. doi:10.3389/fimmu.2018.02838
   PubMed Web of Science ®Google Scholar
• Agus A, Clément K, Sokol H. Gut microbiota-derived metabolites as central regulators in metabolic disorders. Gut. 2021;70(6):1174–1182. doi:10.1136/gutjnl-2020-323071
   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
• Morais LH, Schreiber HL, Mazmanian SK. The gut microbiota–brain axis in behaviour and brain disorders. Nat Rev Microbiol. 2021;19(4):241–255. doi:10.1038/s41579-020-00460-0
   PubMed Web of Science ®Google Scholar
• Korecka A, Dona A, Lahiri S, Tett AJ, Al-Asmakh M, Braniste V, D’Arienzo R, Abbaspour A, Reichardt N, Fujii-Kuriyama Y, et al. Bidirectional communication between the Aryl hydrocarbon Receptor (AhR) and the microbiome tunes host metabolism. NPJ Biofilms Microbiomes. 2016;2(1):16014. doi:10.1038/npjbiofilms.2016.14
   PubMedGoogle Scholar
• Agus A, Planchais J, Sokol H. Gut microbiota regulation of tryptophan metabolism in health and disease. Cell Host Microbe. 2018;23(6):716–724. doi:10.1016/j.chom.2018.05.003
   PubMed Web of Science ®Google Scholar
• Lamas B, Richard ML, Leducq V, Pham H-P, Michel M-L, Da Costa G, Bridonneau C, Jegou S, Hoffmann TW, Natividad JM, 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
• Modoux M, Rolhion N, Mani S, Sokol H. Tryptophan metabolism as a pharmacological target. Trends Pharmacol Sci. 2021;42(1):60–73. doi:10.1016/j.tips.2020.11.006
   PubMed Web of Science ®Google Scholar
• Wrzosek L, Ciocan D, Hugot C, Spatz M, Dupeux M, Houron C, Moal V-L-L, Puchois V, Ferrere G, Trainel N, et al. Microbiota tryptophan metabolism induces aryl hydrocarbon receptor activation and improves alcohol-induced liver injury. Gut. 2021;70(7):1299–1308. doi:10.1136/gutjnl-2020-321565
   PubMed Web of Science ®Google Scholar
• Natividad JM, Agus A, Planchais J, Lamas B, Jarry AC, Martin R, Michel M-L, Chong-Nguyen C, Roussel R, Straube M, et al. Impaired aryl hydrocarbon receptor ligand production by the gut microbiota is a key factor in metabolic syndrome. Cell Metabol. 2018;28(5):737–749.e4. doi:10.1016/j.cmet.2018.07.001
   PubMed Web of Science ®Google Scholar
• Lamas B, Hernandez-Galan L, Galipeau HJ, Constante M, Clarizio A, Jury J, Breyner NM, Caminero A, Rueda G, Hayes CL, et al. Aryl hydrocarbon receptor ligand production by the gut microbiota is decreased in celiac disease leading to intestinal inflammation. Sci Transl Med. 2020;12(566):eaba0624. doi:10.1126/scitranslmed.aba0624
   PubMed Web of Science ®Google Scholar
• Denison MS, Nagy SR. Activation of the aryl hydrocarbon receptor by structurally diverse exogenous and endogenous chemicals. Ann Rev Pharmacol Toxicol. 2003;43(1):309–334. doi:10.1146/annurev.pharmtox.43.100901.135828
   PubMed Web of Science ®Google Scholar
• Marinelli L, Martin-Gallausiaux C, Bourhis J-M, Béguet-Crespel F, Blottière HM, Lapaque N. Identification of the novel role of butyrate as AhR ligand in human intestinal epithelial cells. Sci Rep. 2019;9(1):643. doi:10.1038/s41598-018-37019-2
   PubMedGoogle Scholar
• Zierer J, Jackson MA, Kastenmüller G, Mangino M, Long T, Telenti A, Mohney RP, Small KS, Bell JT, Steves CJ, et al. The fecal metabolome as a functional readout of the gut microbiome. Nat Genet. 2018;50(6):790–795. doi:10.1038/s41588-018-0135-7
   PubMed Web of Science ®Google Scholar
• Matsumoto M, Kibe R, Ooga T, Aiba Y, Kurihara S, Sawaki E, Koga Y, Benno Y. Impact of intestinal microbiota on intestinal luminal metabolome. Sci Rep. 2012;2(1):233. doi:10.1038/srep00233
   PubMedGoogle Scholar
• Jin U-H, Lee S-O, Sridharan G, Lee K, Davidson LA, Jayaraman A, Chapkin RS, Alaniz R, Safe S. Microbiome-derived tryptophan metabolites and their aryl hydrocarbon receptor-dependent agonist and antagonist activities. Mol Pharmacol. 2014;85(5):777–788. doi:10.1124/mol.113.091165
   PubMed Web of Science ®Google Scholar
• Rosser EC, Piper CJM, Matei DE, Blair PA, Rendeiro AF, Orford M, Alber DG, Krausgruber T, Catalan D, Klein N, et al. Microbiota-derived metabolites suppress arthritis by amplifying aryl-hydrocarbon receptor activation in regulatory B cells. Cell Metab. 2020;31(4):837–851.e10. doi:10.1016/j.cmet.2020.03.003
   PubMed Web of Science ®Google Scholar
• Wincent E, Bengtsson J, Bardbori AM, Alsberg T, Luecke S, Rannug U, Rannug A. Inhibition of cytochrome P4501-dependent clearance of the endogenous agonist FICZ as a mechanism for activation of the aryl hydrocarbon receptor. Proc Natl Acad Sci U S A. 2012;109(12):4479–4484. doi:10.1073/pnas.1118467109
   PubMed Web of Science ®Google Scholar
• Schiering C, Wincent E, Metidji A, Iseppon A, Li Y, Potocnik AJ, Omenetti S, Henderson CJ, Wolf CR, Nebert DW, et al. Feedback control of AHR signaling regulates intestinal immunity. Nature. 2017;542(7640):242–245. doi:10.1038/nature21080
   PubMed Web of Science ®Google Scholar
• Guengerich FP. Cytochrome P450s and other enzymes in drug metabolism and toxicity. AAPS J. 2006;8(1):E101–11. doi:10.1208/aapsj080112
   PubMed Web of Science ®Google Scholar
• Yang W, Yu T, Huang X, Bilotta AJ, Xu L, Lu Y, Sun J, Pan F, Zhou J, Zhang W, et al. Intestinal microbiota-derived short-chain fatty acids regulation of immune cell IL-22 production and gut immunity. Nat Commun. 2020;11(1):4457. doi:10.1038/s41467-020-18262-6
   PubMed Web of Science ®Google Scholar
• Manasanch EE, Orlowski RZ. Proteasome inhibitors in cancer therapy. Nat Rev Clin Oncol. 2017;14(7):417–433. doi:10.1038/nrclinonc.2016.206
   PubMed Web of Science ®Google Scholar
• Santiago-Josefat B, Pozo-Guisado E, Mulero-Navarro S, Fernandez-Salguero PM. Proteasome inhibition induces nuclear translocation and transcriptional activation of the dioxin receptor in mouse embryo primary fibroblasts in the absence of xenobiotics. Mol Cell Biol. 2001;21(5):1700–1709. doi:10.1128/MCB.21.5.1700-1709.2001
   PubMed Web of Science ®Google Scholar
• Yin L, Laevsky G, Giardina C. Butyrate suppression of colonocyte NF-κB activation and cellular proteasome activity. J Biol Chem. 2001;276(48):44641–44646. doi:10.1074/jbc.M105170200
   PubMed Web of Science ®Google Scholar
• Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J, deRoos P, Liu H, Cross JR, Pfeffer K, Coffer PJ, et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature. 2013;504(7480):451–455. doi:10.1038/nature12726
   PubMed Web of Science ®Google Scholar
• Stilling RM, van de Wouw M, Clarke G, Stanton C, Dinan TG, Cryan JF. The neuropharmacology of butyrate: the bread and butter of the microbiota-gut-brain axis? Neurochem Int. 2016;99:110–132. doi:10.1016/j.neuint.2016.06.011
   PubMed Web of Science ®Google Scholar
• Krautkramer KA, Fan J, Bäckhed F. Gut microbial metabolites as multi-kingdom intermediates. Nat Rev Microbiol. 2020;18(1):1–18. doi:10.1038/s41579-019-0302-6
   PubMedGoogle Scholar
• Fellows R, Varga-Weisz P. Chromatin dynamics and histone modifications in intestinal microbiota-host crosstalk. Mol Metabol. 2020;38:100925. doi:10.1016/j.molmet.2019.12.005
   PubMed Web of Science ®Google Scholar
• Vyhlídalová B, Krasulová K, Pečinková P, Marcalíková A, Vrzal R, Zemánková L, Vančo J, Trávníček Z, Vondráček J, Karasová M, et al. Gut microbial catabolites of tryptophan are ligands and agonists of the aryl hydrocarbon receptor: a detailed characterization. Int J Mol Sci. 2020;21(7):2614. doi:10.3390/ijms21072614
   PubMed Web of Science ®Google Scholar
• Manzella C, Singhal M, Alrefai WA, Saksena S, Dudeja PK, Gill RK. Serotonin is an endogenous regulator of intestinal CYP1A1 via AhR. Sci Rep. 2018;8(1):6103. doi:10.1038/s41598-018-24213-5
   PubMedGoogle Scholar
• Manzella CR, Ackerman M, Singhal M, Ticho AL, Ceh J, Alrefai WA, Saksena S, Dudeja PK, Gill RK. Serotonin modulates AhR activation by interfering with CYP1A1-mediated clearance of AhR ligands. Cell Physiol Biochem. 2020;54(1):126–141. doi:10.33594/000000209
   PubMedGoogle Scholar
• Jin U-H, Cheng Y, Park H, Davidson LA, Callaway ES, Chapkin RS, Jayaraman A, Asante A, Allred C, Weaver EA, et al. Short chain fatty acids enhance Aryl Hydrocarbon (Ah) responsiveness in mouse colonocytes and Caco-2 human colon cancer cells. Sci Rep. 2017;7(1):10163. doi:10.1038/s41598-017-10824-x
   PubMedGoogle Scholar
• Schnekenburger M, Peng L, Puga A. HDAC1 bound to the Cyp1a1 promoter blocks histone acetylation associated with Ah receptor-mediated trans-activation. Biochim Biophys Acta. 2007;1769(9–10):569–578. doi:10.1016/j.bbaexp.2007.07.002
   PubMedGoogle Scholar
• Wu J, Jiang Z, Zhang H, Liang W, Huang W, Zhang H, Li Y, Wang Z, Wang J, Jia Y, et al. Sodium butyrate attenuates diabetes-induced aortic endothelial dysfunction via P300-mediated transcriptional activation of Nrf2. Free Radical Biol Med. 2018;124:454–465. doi:10.1016/j.freeradbiomed.2018.06.034
   PubMed Web of Science ®Google Scholar
• Garrison PM, Rogers JM, Brackney WR, Denison MS. Effects of histone deacetylase inhibitors on the Ah receptor gene promoter. Archiv Biochem Biophys. 2000;374(2):161–171. doi:10.1006/abbi.1999.1620
   PubMed Web of Science ®Google Scholar
• Alenghat T, Osborne LC, Saenz SA, Kobuley D, Ziegler CGK, Mullican SE, Choi I, Grunberg S, Sinha R, Wynosky-Dolfi M, et al. Histone deacetylase 3 coordinates commensal-bacteria-dependent intestinal homeostasis. Nature. 2013;504(7478):153–157. doi:10.1038/nature12687
   PubMed Web of Science ®Google Scholar
• Dvořák Z, Sokol H, Mani S. Drug mimicry: promiscuous receptors PXR and AhR, and microbial metabolite interactions in the intestine. Trends Pharmacol Sci. 2020;41(12):900–908. doi:10.1016/j.tips.2020.09.013
   PubMed Web of Science ®Google Scholar
• Lefèvre A, Mavel S, Nadal-Desbarats L, Galineau L, Attucci S, Dufour D, Sokol H, Emond P. Validation of a global quantitative analysis methodology of tryptophan metabolites in mice using LC-MS. Talanta. 2019;195:593–598. doi:10.1016/j.talanta.2018.11.094
   PubMed Web of Science ®Google Scholar
• Stepankova M, Bartonkova I, Jiskrova E, Vrzal R, Mani S, Kortagere S, Dvorak Z. Methylindoles and methoxyindoles are agonists and antagonists of human aryl hydrocarbon receptor. Mol Pharmacol. 2018;93(6):631–644. doi:10.1124/mol.118.112151
   PubMed Web of Science ®Google Scholar
• Denison MS, Rogers JM, Rushing SR, Jones CL, Tetangco SC, Heath-Pagliuso S. Analysis of the aryl hydrocarbon receptor (AhR) signal transduction pathway. Curr Protoc Toxicol. 2002;Chapter 4:Unit4.8. doi:10.1002/0471140856.tx0408s11
   PubMedGoogle Scholar