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Current Drug Metabolism


ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

Review Article

Cross-regulatory Circuit Between AHR and Microbiota

Author(s): Jian Ji and Hao Qu*

Volume 20, Issue 1, 2019

Page: [4 - 8] Pages: 5

DOI: 10.2174/1389200219666180129151150

Price: $65


Background: The gut microbes have a close symbiotic relationship with their host. Interactions between host and the microbiota affect the nutritional, immunological, and physiological status of the host. The Aryl Hydrocarbon Receptor (AHR) is a ligand activated transcription factor that mediates the toxicity of xenobiotics. Recently, the relationship between the gut microbiota and AHR has attracted the attention of many researchers.

Methods: We undertook a structured search of bibliographic databases for peer-reviewed research literature.

Results: We found and reviewed 49 peer-reviewed papers dealing with the major aspects related to the crosstalk between AHR and microbiota. The AHR influences the intestinal microbiota population and mediates host-microbe homeostasis. Interestingly, the gut microbiota also produces ligands of AHR from bacterial metabolism and thereby activates the AHR signaling pathway.

Concusion: This review presents current knowledge of the cross-regulatory circuit between the AHR and intestinal microbiota. The findings of this review confirm the importance of AHR-microbiota interactions in health and disease.

Keywords: Aryl hydrocarbon receptor (AHR), ligand, xenobiotics, microbiota, cross-regulatory, homeostasis.

Graphical Abstract
Bonder, M.J.; Kurilshikov, A.; Tigchelaar, E.F.; Mujagic, Z.; Imhann, F.; Vila, A.V.; Deelen, P.; Vatanen, T.; Schirmer, M.; Smeekens, S.P.; Zhernakova, D.V.; Jankipersadsing, S.A.; Jaeger, M.; Oosting, M.; Cenit, M.C.; Masclee, A.A.; Swertz, M.A.; Li, Y.; Kumar, V.; Joosten, L.; Harmsen, H.; Weersma, R.K.; Franke, L.; Hofker, M.H.; Xavier, R.J.; Jonkers, D.; Netea, M.G.; Wijmenga, C.; Fu, J.; Zhernakova, A. The effect of host genetics on the gut microbiome. Nat. Genet., 2016, 48(11), 1407-1412.
Ma, X.; Chen, J.; Tian, Y. Pregnane X receptor as the “sensor and effector” in regulating epigenome. J. Cell. Physiol., 2015, 230(4), 752-757.
Li, Y.; Innocentin, S.; Withers, D.R.; Roberts, N.A.; Gallagher, A.R.; Grigorieva, E.F.; Wilhelm, C.; Veldhoen, M. Exogenous stimuli maintain intraepithelial lymphocytes via aryl hydrocarbon receptor activation. Cell, 2011, 147(3), 629-640.
Takamura, T.; Harama, D.; Fukumoto, S.; Nakamura, Y.; Shimokawa, N.; Ishimaru, K.; Ikegami, S.; Makino, S.; Kitamura, M.; Nakao, A. Lactobacillus bulgaricus OLL1181 activates the aryl hydrocarbon receptor pathway and inhibits colitis. Immunol. Cell Biol., 2011, 89(7), 817-822.
Takamura, T.; Harama, D.; Matsuoka, S.; Shimokawa, N.; Nakamura, Y.; Okumura, K.; Ogawa, H.; Kitamura, M.; Nakao, A. Activation of the aryl hydrocarbon receptor pathway may ameliorate dextran sodium sulfate-induced colitis in mice. Immunol. Cell Biol., 2010, 88(6), 685-689.
Qiu, J.; Heller, J.J.; Guo, X.; Chen, Z.M.; Fish, K.; Fu, Y.X.; Zhou, L. The aryl hydrocarbon receptor regulates gut immunity through modulation of innate lymphoid cells. Immunity, 2012, 36(1), 92-104.
Arsenescu, R.; Arsenescu, V.; Zhong, J.; Nasser, M.; Melinte, R.; Dingle, R.W.; Swanson, H.; de Villiers, W.J. Role of the xenobiotic receptor in inflammatory bowel disease. Inflamm. Bowel Dis., 2011, 17(5), 1149-1162.
Fukumoto, S.; Toshimitsu, T.; Matsuoka, S.; Maruyama, A.; Oh-Oka, K.; Takamura, T.; Nakamura, Y.; Ishimaru, K.; Fujii-Kuriyama, Y.; Ikegami, S.; Itou, H.; Nakao, A. Identification of a probiotic bacteria-derived activator of the aryl hydrocarbon receptor that inhibits colitis. Immunol. Cell Biol., 2014, 92(5), 460-465.
Denison, M.S.; Soshilov, A.A.; He, G.; DeGroot, D.E.; Zhao, B. Exactly the same but different: promiscuity and diversity in the molecular mechanisms of action of the aryl hydrocarbon (dioxin) receptor. Toxicol. Sci., 2011, 124(1), 1-22.
Veldhoen, M.; Duarte, J.H. The aryl hydrocarbon receptor: Fine-tuning the immune-response. Curr. Opin. Immunol., 2010, 22(6), 747-752.
Evans, B.R.; Karchner, S.I.; Allan, L.L.; Pollenz, R.S.; Tanguay, R.L.; Jenny, M.J.; Sherr, D.H.; Hahn, M.E. Repression of aryl hydrocarbon Receptor (AHR) signaling by AHR repressor: Role of DNA binding and competition for AHR nuclear translocator. Mol. Pharmacol., 2008, 73(2), 387-398.
Mimura, J.; Ema, M.; Sogawa, K.; Fujii-Kuriyama, Y. Identification of a novel mechanism of regulation of Ah (dioxin) receptor function. Genes Dev., 1999, 13(1), 20-25.
Denison, M.S.; Pandini, A.; Nagy, S.R.; Baldwin, E.P.; Bonati, L. Ligand binding and activation of the Ah receptor. Chem. Biol. Interact., 2002, 141(1-2), 3-24.
Perdew, G.H.; Babbs, C.F. Production of Ah receptor ligands in rat fecal suspensions containing tryptophan or indole-3-carbinol. Nutr. Cancer, 1991, 16(3-4), 209-218.
Zelante, T.; Iannitti, R.G.; Fallarino, F.; Gargaro, M.; De Luca, A.; Moretti, S.; Bartoli, A.; Romani, L.De; Luca, A.; Moretti, S.; Bartoli, A.; Romani, L. Tryptophan feeding of the IDO1-AHR axis in host-microbial symbiosis. Front. Immunol., 2014, 5, 640.
Jin, U.H.; Lee, S.O.; Sridharan, G.; Lee, K.; Davidson, L.A.; Jayaraman, A.; Chapkin, R.S.; 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.
Hubbard, T.D.; Murray, I.A.; Bisson, W.H.; Lahoti, T.S.; Gowda, K.; Amin, S.G.; Patterson, A.D.; Perdew, G.H. Adaptation of the human aryl hydrocarbon receptor to sense microbiota-derived indoles. Sci. Rep., 2015, 5, 12689.
Moura-Alves, P.; Faé, K.; Houthuys, E.; Dorhoi, A.; Kreuchwig, A.; Furkert, J.; Barison, N.; Diehl, A.; Munder, A.; Constant, P.; Skrahina, T.; Guhlich-Bornhof, U.; Klemm, M.; Koehler, A.B.; Bandermann, S.; Goosmann, C.; Mollenkopf, H.J.; Hurwitz, R.; Brinkmann, V.; Fillatreau, S.; Daffe, M.; Tümmler, B.; Kolbe, M.; Oschkinat, H.; Krause, G.; Kaufmann, S.H. AhR sensing of bacterial pigments regulates antibacterial defence. Nature, 2014, 512(7515), 387-392.
Lee, H.U.; McPherson, Z.E.; Tan, B.; Korecka, A.; Pettersson, S. Host-microbiome interactions: The aryl hydrocarbon receptor and the central nervous system. J. Mol. Med. (Berl.), 2017, 95(1), 29-39.
Noakes, R. The aryl hydrocarbon receptor: A review of its role in the physiology and pathology of the integument and its relationship to the tryptophan metabolism. Int. J. Tryptophan Res., 2015, 8, 7-18.
Kawajiri, K.; Fujii-Kuriyama, Y. The aryl hydrocarbon receptor: A multifunctional chemical sensor for host defense and homeostatic maintenance. Exp. Anim., 2017, 66(2), 75-89.
Qin, J.; Li, R.; Raes, J.; Arumugam, M.; Burgdorf, K.S.; Manichanh, C.; Nielsen, T.; Pons, N.; Levenez, F.; Yamada, T.; Mende, D.R.; Li, J.; Xu, J.; Li, S.; Li, D.; Cao, J.; Wang, B.; Liang, H.; Zheng, H.; Xie, Y.; Tap, J.; Lepage, P.; Bertalan, M.; Batto, J.M.; Hansen, T.; Le Paslier, D.; Linneberg, A.; Nielsen, H.B.; Pelletier, E.; Renault, P.; Sicheritz-Ponten, T.; Turner, K.; Zhu, H.; Yu, C.; Li, S.; Jian, M.; Zhou, Y.; Li, Y.; Zhang, X.; Li, S.; Qin, N.; Yang, H.; Wang, J.; Brunak, S.; Doré, J.; Guarner, F.; Kristiansen, K.; Pedersen, O.; Parkhill, J.; Weissenbach, J.; Bork, P.; Ehrlich, S.D.; Wang, J. A human gut microbial gene catalogue established by metagenomic sequencing. Nature, 2010, 464(7285), 59-65.
Kamada, N.; Seo, S.U.; Chen, G.Y.; Núñez, G. Role of the gut microbiota in immunity and inflammatory disease. Nat. Rev. Immunol., 2013, 13(5), 321-335.
Grönlund, M.M.; Grześkowiak, Ł.; Isolauri, E.; Salminen, S. Influence of mother’s intestinal microbiota on gut colonization in the infant. Gut Microbes, 2011, 2(4), 227-233.
Vaishampayan, P.A.; Kuehl, J.V.; Froula, J.L.; Morgan, J.L.; Ochman, H.; Francino, M.P. Comparative metagenomics and population dynamics of the gut microbiota in mother and infant. Genome Biol. Evol., 2010, 2, 53-66.
Avershina, E.; Storrø, O.; Øien, T.; Johnsen, R.; Pope, P.; Rudi, K. Major faecal microbiota shifts in composition and diversity with age in a geographically restricted cohort of mothers and their children. FEMS Microbiol. Ecol., 2014, 87(1), 280-290.
Costello, E.K.; Lauber, C.L.; Hamady, M.; Fierer, N.; Gordon, J.I.; Knight, R. Bacterial community variation in human body habitats across space and time. Science, 2009, 326(5960), 1694-1697.
Yatsunenko, T.; Rey, F.E.; Manary, M.J.; Trehan, I.; Dominguez-Bello, M.G.; Contreras, M.; Magris, M.; Hidalgo, G.; Baldassano, R.N.; Anokhin, A.P.; Heath, A.C.; Warner, B.; Reeder, J.; Kuczynski, J.; Caporaso, J.G.; Lozupone, C.A.; Lauber, C.; Clemente, J.C.; Knights, D.; Knight, R.; Gordon, J.I. Human gut microbiome viewed across age and geography. Nature, 2012, 486(7402), 222-227.
Dominguez-Bello, M.G.; Blaser, M.J.; Ley, R.E.; Knight, R. Development of the human gastrointestinal microbiota and insights from high-throughput sequencing. Gastroenterology, 2011, 140(6), 1713-1719.
Gill, S.R.; Pop, M.; Deboy, R.T.; Eckburg, P.B.; Turnbaugh, P.J.; Samuel, B.S.; Gordon, J.I.; Relman, D.A.; Fraser-Liggett, C.M.; Nelson, K.E. Metagenomic analysis of the human distal gut microbiome. Science, 2006, 312(5778), 1355-1359.
Murray, I.A.; Nichols, R.G.; Zhang, L.; Patterson, A.D.; Perdew, G.H. Expression of the aryl hydrocarbon receptor contributes to the establishment of intestinal microbial community structure in mice. Sci. Rep., 2016, 6, 33969.
Korecka, A.; Dona, A.; Lahiri, S.; Tett, A.J.; Al-Asmakh, M.; Braniste, V.; D’Arienzo, R.; Abbaspour, A.; Reichardt, N.; Fujii-Kuriyama, Y.; Rafter, J.; Narbad, A.; Holmes, E.; Nicholson, J.; Arulampalam, V.; Pettersson, S. Bidirectional communication between the Aryl hydrocarbon Receptor (AhR) and the microbiome tunes host metabolism. NPJ Biofilms Microbiomes, 2016, 2, 16014.
Zhang, L.; Nichols, R.G.; Patterson, A.D. The aryl hydrocarbon receptor as a moderator of host-microbiota communication. Curr. Opin. Toxicol., 2017, 2, 30-35.
Lamas, B.; Richard, M.L.; Leducq, V.; Pham, H.P.; Michel, M.L.; Da Costa, G.; Bridonneau, C.; Jegou, S.; Hoffmann, T.W.; Natividad, J.M.; Brot, L.; Taleb, S.; Couturier-Maillard, A.; Nion-Larmurier, I.; Merabtene, F.; Seksik, P.; Bourrier, A.; Cosnes, J.; Ryffel, B.; Beaugerie, L.; Launay, J.M.; Langella, P.; Xavier, R.J.; Sokol, H. CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. Nat. Med., 2016, 22(6), 598-605.
Zelante, T.; Iannitti, R.G.; Cunha, C.; De Luca, A.; Giovannini, G.; Pieraccini, G.; Zecchi, R.; D’Angelo, C.; Massi-Benedetti, C.; Fallarino, F.; Carvalho, A.; Puccetti, P.; Romani, L. Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity, 2013, 39(2), 372-385.
Liévin-Le Moal, V.; Servin, A.L. Anti-infective activities of lactobacillus strains in the human intestinal microbiota: From probiotics to gastrointestinal anti-infectious biotherapeutic agents. Clin. Microbiol. Rev., 2014, 27(2), 167-199.
Engen, S.A.; Rørvik, G.H.; Schreurs, O.; Blix, I.J.; Schenck, K. The oral commensal Streptococcus mitis activates the aryl hydrocarbon receptor in human oral epithelial cells. Int. J. Oral Sci., 2017, 9(3), 145-150.
Rothhammer, V.; Mascanfroni, I.D.; Bunse, L.; Takenaka, M.C.; Kenison, J.E.; Mayo, L.; Chao, C.C.; Patel, B.; Yan, R.; Blain, M.; Alvarez, J.I.; Kébir, H.; Anandasabapathy, N.; Izquierdo, G.; Jung, S.; Obholzer, N.; Pochet, N.; Clish, C.B.; Prinz, M.; Prat, A.; Antel, J.; Quintana, F.J. 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.
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(10), 1221-1227.
Ley, R.E.; Peterson, D.A.; Gordon, J.I. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell, 2006, 124(4), 837-848.
Stefka, A.T.; Feehley, T.; Tripathi, P.; Qiu, J.; McCoy, K.; Mazmanian, S.K.; Tjota, M.Y.; Seo, G.Y.; Cao, S.; Theriault, B.R.; Antonopoulos, D.A.; Zhou, L.; Chang, E.B.; Fu, Y.X.; Nagler, C.R. Commensal bacteria protect against food allergen sensitization. Proc. Natl. Acad. Sci. USA, 2014, 111(36), 13145-13150.
Machowinski, A.; Krämer, H.J.; Hort, W.; Mayser, P. Pityriacitrin--a potent UV filter produced by Malassezia furfur and its effect on human skin microflora. Mycoses, 2006, 49(5), 388-392.
Gaitanis, G.; Magiatis, P.; Stathopoulou, K.; Bassukas, I.D.; Alexopoulos, E.C.; Velegraki, A.; Skaltsounis, A.L. AhR ligands, malassezin, and indolo [3,2-b]carbazole are selectively produced by Malassezia furfur strains isolated from seborrheic dermatitis. J. Invest. Dermatol., 2008, 128(7), 1620-1625.
Vlachos, C.; Schulte, B.M.; Magiatis, P.; Adema, G.J.; Gaitanis, G. Malassezia-derived indoles activate the aryl hydrocarbon receptor and inhibit Toll-like receptor-induced maturation in monocyte-derived dendritic cells. Br. J. Dermatol., 2012, 167(3), 496-505.
Zhang, L.; Nichols, R.G.; Correll, J.; Murray, I.A.; Tanaka, N.; Smith, P.B.; Hubbard, T.D.; Sebastian, A.; Albert, I.; Hatzakis, E.; Gonzalez, F.J.; Perdew, G.H.; Patterson, A.D. Persistent organic pollutants modify gut microbiota-host metabolic homeostasis in mice through aryl hydrocarbon receptor activation. Environ. Health Perspect., 2015, 123(7), 679-688.
Lefever, D.E.; Xu, J.; Chen, Y.; Huang, G.; Tamas, N.; Guo, T.L. TCDD modulation of gut microbiome correlated with liver and immune toxicity in streptozotocin (STZ)-induced hyperglycemic mice. Toxicol. Appl. Pharmacol., 2016, 304, 48-58.
Haas, K.; Weighardt, H.; Deenen, R.; Köhrer, K.; Clausen, B.; Zahner, S.; Boukamp, P.; Bloch, W.; Krutmann, J.; Esser, C. Aryl hydrocarbon receptor in keratinocytes is essential for murine skin barrier integrity. J. Invest. Dermatol., 2016, 136(11), 2260-2269.
Bersten, D.C.; Sullivan, A.E.; Peet, D.J.; Whitelaw, M.L. bHLH-PAS proteins in cancer. Nat. Rev. Cancer, 2013, 13(12), 827-841.
Quintana, F.J.; Sherr, D.H. Aryl hydrocarbon receptor control of adaptive immunity. Pharmacol. Rev., 2013, 65(4), 1148-1161.

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