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Cited by 424Gut microbiota and healthTryptophan and brain disordersAnimal Nutrition and Physiology

Gut Microbiota-Derived Tryptophan Metabolites Maintain Gut and Systemic Homeostasis

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Su, Xiaomin, Gao, Yunhuan, Yang, Rongcun·2022·Cells
DOI 10.3390/cells11152296PMC PMC9330295
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Abstract

Tryptophan is an essential amino acid from dietary proteins. It can be metabolized into different metabolites in both the gut microbiota and tissue cells. Tryptophan metabolites such as indole-3-lactate (ILA), indole-3-acrylate (IAC), indole-3-propionate (IPA), indole-3-aldehyde (IAID), indoleacetic acid (IAA), indole-3-acetaldehyde and Kyn can be produced by intestinal microorganisms through direct Trp transformation and also, partly, the kynurenine (Kyn) pathway. These metabolites play a critical role in maintaining the homeostasis of the gut and systematic immunity and also potentially affect the occurrence and development of diseases such as inflammatory bowel diseases, tumors, obesity and metabolic syndrome, diseases in the nervous system, infectious diseases, vascular inflammation and cardiovascular diseases and hepatic fibrosis. They can not only promote the differentiation and function of anti-inflammatory macrophages, Treg cells, CD4+CD8αα+ regulatory cells, IL-10+ and/or IL-35+B regulatory cells but also IL-22-producing innate lymphoid cells 3 (ILC3), which are involved in maintaining the gut mucosal homeostasis. These findings have important consequences in the immunotherapy against tumor and other immune-associated diseases. We will summarize here the recent advances in understanding the generation and regulation of tryptophan metabolites in the gut microbiota, the role of gut microbiota-derived tryptophan metabolites in different immune cells, the occurrence and development of diseases and immunotherapy against immune-associated diseases.

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  • Many postbiotics, including short-chain fatty acids (SCFAs) and peptidoglycans, have anti-inflammatory effects by regulating the activity of inflammatory immune cells and reducing the production of inflammatory cytokines, which is critical for protecting against chronic inflammation and keeping the gut in good working order.

    “Many postbiotics, including short-chain fatty acids (SCFAs) and peptidoglycans, have anti-inflammatory effects. They can regulate the activity of inflammatory immune cells and reduce the production of inflammatory cytokines. This anti-inflammatory impact is critical for protecting against chronic inflammation and keeping the gut in good working order.”

    From Unveiling the therapeutic symphony of probiotics, prebiotics, and postbiotics in gut-immune harmony (2024) · cites this paper as [30]

    Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

  • Postbiotics can help the immune system learn to distinguish between innocuous and hazardous chemicals (immunological tolerance), preventing inappropriate immune responses to innocuous antigens and allergens by instructing the immune system and encouraging the growth of regulatory immune cells.

    “Postbiotics can help the immune system learn to distinguish between innocuous and hazardous chemicals, a process known as immunological tolerance. Postbiotics aid in preventing inappropriate immune responses to innocuous antigens and allergens by instructing the immune system and encouraging the growth of regulatory immune cells.”

    From Unveiling the therapeutic symphony of probiotics, prebiotics, and postbiotics in gut-immune harmony (2024) · cites this paper as [30]

    Section 3.5 (page not available) says gut microbiota-derived tryptophan metabolites can drive the formation of regulatory intestinal cells that promote tolerance to dietary antigens. Sections 3.2 and 3.3 also describe effects on regulatory immune cells, and section 5 reports protection against food allergy in mice. The paper addresses specific tryptophan metabolites, however, not postbiotics generally or an established ability to distinguish innocuous from hazardous chemicals. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Probiotics and prebiotics improve glucose metabolism and decrease inflammation in diabetes patients by altering the makeup and function of the gut microbiota.

    “Glycemic management and insulin sensitivity in people with type 2 diabetes have been studied as a possible benefit of probiotics and prebiotics. These bioactive compounds improve glucose metabolism and decrease inflammation in diabetes patients by altering the makeup and function of the gut microbiota.”

    From Unveiling the therapeutic symphony of probiotics, prebiotics, and postbiotics in gut-immune harmony (2024) · cites this paper as [30]

    Section 2.2 reports that fructooligosaccharides alter gut microbiome profiles, and section 4.3 says microbial metabolites and components affect type 2 diabetes through inflammation and metabolism (pages not provided). Neither passage shows that probiotics or prebiotics improve glucose metabolism or reduce inflammation in diabetes patients; the claimed patient benefit is unsupported. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • Evidence is mounting that probiotics and prebiotics may be useful in controlling autoimmune illnesses including rheumatoid arthritis and multiple sclerosis by altering the composition of the gut flora, affecting immunological dysregulation and potentially reducing autoimmune reactions.

    “Evidence is mounting that probiotics and prebiotics may be useful in controlling autoimmune illnesses including rheumatoid arthritis and multiple sclerosis by altering the composition of the gut flora. These bioactive compounds affect immunological dysregulation and might reduce autoimmune reactions.”

    From Unveiling the therapeutic symphony of probiotics, prebiotics, and postbiotics in gut-immune harmony (2024) · cites this paper as [30]

    Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

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  • Probiotics and prebiotics can mitigate allergy diseases including eczema and rhinitis by regulating the balance between Th1 and Th2 immune responses.

    “It has been investigated whether or not probiotics and prebiotics can mitigate allergy diseases including eczema and rhinitis. They are essential in the regulation of the balance between Th1 and Th2 immune responses, which are responsible for the development of allergic disorders.”

    From Unveiling the therapeutic symphony of probiotics, prebiotics, and postbiotics in gut-immune harmony (2024) · cites this paper as [30]

    Section 5 reports that fructooligosaccharides protect mice against experimentally induced food allergy, which supports a narrower claim about a prebiotic and allergy. It attributes the effect to a Th17/Treg balance, not a Th1/Th2 balance; the passages do not support the claims about probiotics, eczema, or rhinitis. (LLM, conf=0.84)

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Research works printed but not linked: 159

  1. [3]Hubbard T.D. Murray I.A. Perdew G.H. Indole and Tryptophan Metabolism: Endogenous and Dietary Routes to Ah Receptor Activation Drug Metab. Dispos. 2015 43 1522 1535 10.1124/dmd.115.064246 26041783 PMC4576673 · DOI
  2. [4]Whitehead T.R. Price N.P. Drake H.L. Cotta M.A. Catabolic pathway for the production of skatole and indoleacetic acid by the acetogen Clostridium drakei, Clostridium scatologenes, and swine manure Appl. Environ. Microbiol. 2008 74 1950 1953 10.1128/AEM.02458-07 18223109 PMC2268313 · DOI
  3. [5]Smith E.A. Macfarlane G.T. Enumeration of human colonic bacteria producing phenolic and indolic compounds: Effects of pH, carbohydrate availability and retention time on dissimilatory aromatic amino acid metabolism J. Appl. Bacteriol. 1996 81 288 302 10.1111/j.1365-2672.1996.tb04331.x 8810056 · DOI
  4. [6]Yokoyama M.T. Carlson J.R. Microbial metabolites of tryptophan in the intestinal tract with special reference to skatole Am. J. Clin. Nutr. 1979 32 173 178 10.1093/ajcn/32.1.173 367144 · DOI
  5. [7]Vujkovic-Cvijin I. Dunham R.M. Iwai S. Maher M.C. Albright R.G. Broadhurst M.J. Hernandez R.D. Lederman M.M. Huang Y. Somsouk M. Dysbiosis of the gut microbiota is associated with HIV disease progression and tryptophan catabolism Sci. Transl. Med. 2013 5 193ra91 10.1126/scitranslmed.3006438 PMC4094294 23843452 · DOI
  6. [8]Bansal T. Alaniz R.C. Wood T.K. Jayaraman A. The bacterial signal indole increases epithelial-cell tight-junction resistance and attenuates indicators of inflammation Proc. Natl. Acad. Sci. USA 2010 107 228 233 10.1073/pnas.0906112107 19966295 PMC2806735 · DOI · Paper page
  7. [9]Mawe G.M. Hoffman J.M. Serotonin signalling in the gut--functions, dysfunctions and therapeutic targets Nat. Rev. Gastroenterol. Hepatol. 2013 10 473 486 10.1038/nrgastro.2013.105 23797870 PMC4048923 · DOI · Paper page
  8. [10]Holst J.J. The physiology of glucagon-like peptide 1 Physiol. Rev. 2007 87 1409 1439 10.1152/physrev.00034.2006 17928588 · DOI · Paper page
  9. [11]Hill D.A. Artis D. Intestinal bacteria and the regulation of immune cell homeostasis Annu. Rev. Immunol. 2010 28 623 667 10.1146/annurev-immunol-030409-101330 20192812 PMC5610356 · DOI
  10. [12]Hooper L.V. Littman D.R. Macpherson A.J. Interactions between the microbiota and the immune system Science 2012 336 1268 1273 10.1126/science.1223490 22674334 PMC4420145 · DOI · Paper page
  11. [13]Shinde R. Hezaveh K. Halaby M.J. Kloetgen A. Chakravarthy A. da Silva Medina T. Deol R. Manion K.P. Baglaenko Y. Eldh M. Apoptotic cell-induced AhR activity is required for immunological tolerance and suppression of systemic lupus erythematosus in mice and humans Nat. Immunol. 2018 19 571 582 10.1038/s41590-018-0107-1 29760532 PMC5976527 · DOI
  12. [14]Manni G. Mondanelli G. Scalisi G. Pallotta M.T. Nardi D. Padiglioni E. Romani R. Talesa V.N. Puccetti P. Fallarino F. Pharmacologic Induction of Endotoxin Tolerance in Dendritic Cells by L-Kynurenine Front. Immunol. 2020 11 292 10.3389/fimmu.2020.00292 32226425 PMC7081078 · DOI
  13. [15]Liu Y. Liang X. Dong W. Fang Y. Lv J. Zhang T. Fiskesund R. Xie J. Liu J. Yin X. Tumor-Repopulating Cells Induce PD-1 Expression in CD8+ T Cells by Transferring Kynurenine and AhR Activation Cancer Cell 2018 33 480 494.e7 10.1016/j.ccell.2018.02.005 29533786 · DOI · Paper page
  14. [16]Piper C.J.M. Rosser E.C. Oleinika K. Nistala K. Krausgruber T. Rendeiro A.F. Banos A. Drozdov I. Villa M. Thomson S. Aryl Hydrocarbon Receptor Contributes to the Transcriptional Program of IL-10-Producing Regulatory B Cells Cell Rep. 2019 29 1878 1892.e7 10.1016/j.celrep.2019.10.018 31722204 PMC6856759 · DOI
  15. [17]Cervantes-Barragan L. Chai J.N. Tianero M.D. Di Luccia B. Ahern P.P. Merriman J. Cortez V.S. Caparon M.G. Donia M.S. Gilfillan S. Lactobacillus reuteri induces gut intraepithelial CD4+CD8α+ T cells Science 2017 357 806 810 10.1126/science.aah5825 28775213 PMC5687812 · DOI · Paper page
  16. [18]Zelante T. Iannitti R.G. Fallarino F. Gargaro M. 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 10.3389/fimmu.2014.00640 25566253 PMC4266093 · DOI
  17. [19]Schwarcz R. Stone T.W. The kynurenine pathway and the brain: Challenges, controversies and promises Neuropharmacology 2017 112 237 247 10.1016/j.neuropharm.2016.08.003 27511838 PMC5803785 · DOI
  18. [20]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. CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands Nat. Med. 2016 22 598 605 10.1038/nm.4102 27158904 PMC5087285 · DOI · Paper page
  19. [21]Shiomi Y. Nishiumi S. Ooi M. Hatano N. Shinohara M. Yoshie T. Kondo Y. Furumatsu K. Shiomi H. Kutsumi H. GCMS-based metabolomic study in mice with colitis induced by dextran sulfate sodium Inflamm. Bowel Dis. 2011 17 2261 2274 10.1002/ibd.21616 21287666 · DOI
  20. [22]Botticelli A. Cerbelli B. Lionetto L. Zizzari I. Salati M. Pisano A. Federica M. Simmaco M. Nuti M. Marchetti P. Can IDO activity predict primary resistance to anti-PD-1 treatment in NSCLC? J. Transl. Med. 2018 16 219 10.1186/s12967-018-1595-3 30081936 PMC6080500 · DOI · Paper page
  21. [23]Roager H.M. Licht T.R. Microbial tryptophan catabolites in health and disease Nat. Commun. 2018 9 3294 10.1038/s41467-018-05470-4 30120222 PMC6098093 · DOI · Paper page
  22. [24]Gao J. Xu K. Liu H. Liu G. Bai M. Peng C. Li T. Yin Y. Impact of the Gut Microbiota on Intestinal Immunity Mediated by Tryptophan Metabolism Front. Cell. Infect. Microbiol. 2018 8 13 10.3389/fcimb.2018.00013 29468141 PMC5808205 · DOI
  23. [25]Khoshnevisan K. Chehrehgosha M. Conant M. Meftah A.M. Baharifar H. Ejtahed H.S. Angoorani P. Gholami M. Sharifi F. Maleki H. Interactive relationship between Trp metabolites and gut microbiota: The impact on human pathology of disease J. Appl. Microbiol. 2022 132 4186 4207 10.1111/jam.15533 35304801 · DOI
  24. [27]Dodd D. Spitzer M.H. Van Treuren W. Merrill B.D. Hryckowian A.J. Higginbottom S.K. Le A. Cowan T.M. Nolan G.P. Fischbach M.A. A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites Nature 2017 551 648 652 10.1038/nature24661 29168502 PMC5850949 · DOI · Paper page
  25. [28]Russell W.R. Duncan S.H. Scobbie L. Duncan G. Cantlay L. Calder A.G. Anderson S.E. Flint H.J. Major phenylpropanoid-derived metabolites in the human gut can arise from microbial fermentation of protein Mol. Nutr. Food Res. 2013 57 523 535 10.1002/mnfr.201200594 23349065 · DOI · Paper page
  26. [29]Wlodarska M. Luo C. Kolde R. d’Hennezel E. Annand J.W. Heim C.E. Krastel P. Schmitt E.K. Omar A.S. Creasey E.A. Indoleacrylic Acid Produced by Commensal Peptostreptococcus Species Suppresses Inflammation Cell Host Microbe 2017 22 25 37.e6 10.1016/j.chom.2017.06.007 28704649 PMC5672633 · DOI
  27. [30]Williams B.B. Van Benschoten A.H. Cimermancic P. Donia M.S. Zimmermann M. Taketani M. Ishihara A. Kashyap P.C. Fraser J.S. Fischbach M.A. Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine Cell Host Microbe 2014 16 495 503 10.1016/j.chom.2014.09.001 25263219 PMC4260654 · DOI · Paper page
  28. [31]Honore A.H. Aunsbjerg S.D. Ebrahimi P. Thorsen M. Benfeldt C. Knochel S. Skov T. Metabolic footprinting for investigation of antifungal properties of Lactobacillus paracasei Anal. Bioanal. Chem. 2016 408 83 96 10.1007/s00216-015-9103-6 26573172 · DOI
  29. [32]Wikoff W.R. Anfora A.T. Liu J. Schultz P.G. Lesley S.A. Peters E.C. Siuzdak G. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites Proc. Natl. Acad. Sci. USA 2009 106 3698 3703 10.1073/pnas.0812874106 19234110 PMC2656143 · DOI · Paper page
  30. [33]Lavelle A. Sokol H. Gut microbiota-derived metabolites as key actors in inflammatory bowel disease Nat. Rev. Gastroenterol. Hepatol. 2020 17 223 237 10.1038/s41575-019-0258-z 32076145 · DOI · Paper page
  31. [35]Wilck N. Matus M.G. Kearney S.M. Olesen S.W. Forslund K. Bartolomaeus H. Haase S. Mahler A. Balogh A. Marko L. Salt-responsive gut commensal modulates TH17 axis and disease Nature 2017 551 585 589 10.1038/nature24628 29143823 PMC6070150 · DOI · Paper page
  32. [36]Smith E.A. Macfarlane G.T. Formation of Phenolic and Indolic Compounds by Anaerobic Bacteria in the Human Large Intestine Microb. Ecol. 1997 33 180 188 10.1007/s002489900020 9115181 PMC13589001 · DOI
  33. [37]Koga J. Adachi T. Hidaka H. Molecular cloning of the gene for indolepyruvate decarboxylase from Enterobacter cloacae Mol. Gen. Genet. 1991 226 10 16 10.1007/BF00273581 2034209 · DOI
  34. [38]Honeyfield D.C. Carlson J.R. Effect of Indoleacetic Acid and Related Indoles on Lactobacillus sp. Strain 11201 Growth, Indoleacetic Acid Catabolism, and 3-Methylindole Formation Appl. Environ. Microbiol. 1990 56 1373 1377 10.1128/aem.56.5.1373-1377.1990 16348189 PMC184413 · DOI
  35. [39]Hamady Z.Z.R. Farrar M.D. Whitehead T.R. Holland K.T. Lodge J.P.A. Carding S.R. Identification and use of the putative Bacteroides ovatus xylanase promoter for the inducible production of recombinant human proteins Microbiology 2008 154 3165 3174 10.1099/mic.0.2008/019109-0 18832322 · DOI
  36. [40]Cook R.T. Schlueter A.J. Coleman R.A. Tygrett L. Ballas Z.K. Jerrells T.R. Nashelsky M.B. Ray N.B. Haugen T.H. Waldschmidt T.J. Thymocytes, pre-B cells, and organ changes in a mouse model of chronic ethanol ingestion—Absence of subset-specific glucocorticoid-induced immune cell loss Alcohol. Clin. Exp. Res. 2007 31 1746 1758 10.1111/j.1530-0277.2007.00478.x 17681030 PMC2190628 · DOI
  37. [41]Colabroy K.L. Begley T.P. Tryptophan catabolism: Identification and characterization of a new degradative pathway J. Bacteriol. 2005 187 7866 7869 10.1128/JB.187.22.7866-7869.2005 16267312 PMC1280306 · DOI
  38. [42]Hasegawa Y. Muraki T. Tokuyama T. Iwaki H. Tatsuno M. Lau P.C. A novel degradative pathway of 2-nitrobenzoate via 3-hydroxyanthranilate in Pseudomonas fluorescens strain KU-7 FEMS Microbiol. Lett. 2000 190 185 190 10.1111/j.1574-6968.2000.tb09284.x 11034277 · DOI
  39. [43]Cheng H. Liu J. Zhang D. Wang J. Tan Y. Feng W. Peng C. Ginsenoside Rg1 Alleviates Acute Ulcerative Colitis by Modulating Gut Microbiota and Microbial Tryptophan Metabolism Front. Immunol. 2022 13 817600 10.3389/fimmu.2022.817600 35655785 PMC9152015 · DOI
  40. [44]Yang X. Dong B. An L. Zhang Q. Chen Y. Wang H. Song Z. Ginsenoside Rb1 ameliorates Glycemic Disorder in Mice with High Fat Diet-Induced Obesity via Regulating Gut Microbiota and Amino Acid Metabolism Front. Pharmacol. 2021 12 756491 10.3389/fphar.2021.756491 34899310 PMC8654325 · DOI
  41. [45]Borisova M.A. Snytnikova O.A. Litvinova E.A. Achasova K.M. Babochkina T.I. Pindyurin A.V. Tsentalovich Y.P. Kozhevnikova E.N. Fucose Ameliorates Tryptophan Metabolism and Behavioral Abnormalities in a Mouse Model of Chronic Colitis Nutrients 2020 12 445 10.3390/nu12020445 PMC7071335 32053891 · DOI
  42. [46]Yan X. Yan J. Xiang Q. Wang F. Dai H. Huang K. Fang L. Yao H. Wang L. Zhang W. Fructooligosaccharides protect against OVA-induced food allergy in mice by regulating the Th17/Treg cell balance using tryptophan metabolites Food Funct. 2021 12 3191 3205 10.1039/D0FO03371E 33735338 · DOI
  43. [47]Huang J. Liu D. Wang Y. Liu L. Li J. Yuan J. Jiang Z. Jiang Z. Hsiao W.W. Liu H. Ginseng polysaccharides alter the gut microbiota and kynurenine/tryptophan ratio, potentiating the antitumour effect of antiprogrammed cell death 1/programmed cell death ligand 1 (anti-PD-1/PD-L1) immunotherapy Gut 2022 71 734 745 10.1136/gutjnl-2020-321031 34006584 PMC8921579 · DOI · Paper page
  44. [48]Yang W. Ren D. Zhao Y. Liu L. Yang X. Fuzhuan Brick Tea Polysaccharide Improved Ulcerative Colitis in Association with Gut Microbiota-Derived Tryptophan Metabolism J. Agric. Food Chem. 2021 69 8448 8459 10.1021/acs.jafc.1c02774 34313113 · DOI
  45. [49]Xu Y. Zhang Z. Wang B. He X. Tang J. Peng W. Zhou J. Wang Y. Flammulina velutipes Polysaccharides Modulate Gut Microbiota and Alleviate Carbon Tetrachloride-Induced Hepatic Oxidative Injury in Mice Front. Microbiol. 2022 13 847653 10.3389/fmicb.2022.847653 35401429 PMC8986159 · DOI
  46. [50]Lin H. Meng L. Sun Z. Sun S. Huang X. Lin N. Zhang J. Lu W. Yang Q. Chi J. Yellow Wine Polyphenolic Compound Protects Against Doxorubicin-Induced Cardiotoxicity by Modulating the Composition and Metabolic Function of the Gut Microbiota Circ. Heart Fail. 2021 14 e008220 10.1161/CIRCHEARTFAILURE.120.008220 34665676 · DOI
  47. [51]Jiao C. Zhang Q. Yang M. Ma J. Zhao X. Tang N. Dai M. Li Q. Jiang Z. Huang X. Shenling Baizhu San ameliorates ulcerative colitis by regulating the gut microbiota and its tryptophan metabolites: A complementary medicine to mesalamine J. Ethnopharmacol. 2022 291 115145 10.1016/j.jep.2022.115145 35219821 · DOI
  48. [52]Zhao W. Guo M. Feng J. Gu Z. Zhao J. Zhang H. Wang G. Chen W. Myristica fragrans Extract Regulates Gut Microbes and Metabolites to Attenuate Hepatic Inflammation and Lipid Metabolism Disorders via the AhR-FAS and NF-kappaB Signaling Pathways in Mice with Non-Alcoholic Fatty Liver Disease Nutrients 2022 14 1699 10.3390/nu14091699 35565666 PMC9104743 · DOI
  49. [53]Hu S. Luo L. Bian X. Liu R.H. Zhao S. Chen Y. Sun K. Jiang J. Liu Z. Zeng L. Pu-erh Tea Restored Circadian Rhythm Disruption by Regulating Tryptophan Metabolism J. Agric. Food Chem. 2022 70 5610 5623 10.1021/acs.jafc.2c01883 35475616 · DOI
  50. [54]Sun Z. Li J. Wang W. Liu Y. Liu J. Jiang H. Lu Q. Ding P. Shi R. Zhao X. Qingchang Wenzhong Decoction Accelerates Intestinal Mucosal Healing Through Modulation of Dysregulated Gut Microbiome, Intestinal Barrier and Immune Responses in Mice Front. Pharmacol. 2021 12 738152 10.3389/fphar.2021.738152 34557102 PMC8452913 · DOI
  51. [55]Yang K. Jian S. Wen C. Guo D. Liao P. Wen J. Kuang T. Han S. Liu Q. Deng B. Gallnut Tannic Acid Exerts Anti-stress Effects on Stress-Induced Inflammatory Response, Dysbiotic Gut Microbiota, and Alterations of Serum Metabolic Profile in Beagle Dogs Front. Nutr. 2022 9 847966 10.3389/fnut.2022.847966 35571952 PMC9094144 · DOI
  52. [56]Wan Y. Yang L. Li H. Ren H. Zhu K. Dong Z. Jiang S. Shang E. Qian D. Duan J. Zingiber officinale and Panax ginseng ameliorate ulcerative colitis in mice via modulating gut microbiota and its metabolites J. Chromatogr. B 2022 1203 123313 10.1016/j.jchromb.2022.123313 35662877 · DOI
  53. [57]Ren Q. Cheng L. Guo F. Tao S. Zhang C. Ma L. Fu P. Fisetin Improves Hyperuricemia-Induced Chronic Kidney Disease via Regulating Gut Microbiota-Mediated Tryptophan Metabolism and Aryl Hydrocarbon Receptor Activation J. Agric. Food Chem. 2021 69 10932 10942 10.1021/acs.jafc.1c03449 34505780 · DOI
  54. [58]Yu X. Jin Y. Zhou W. Xiao T. Wu Z. Su J. Gao H. Shen P. Zheng B. Luo Q. Rifaximin Modulates the Gut Microbiota to Prevent Hepatic Encephalopathy in Liver Cirrhosis without Impacting the Resistome Front. Cell. Infect. Microbiol. 2021 11 761192 10.3389/fcimb.2021.761192 35118004 PMC8804384 · DOI
  55. [59]Hu W. Huang L. Zhou Z. Yin L. Tang J. Diallyl Disulfide (DADS) Ameliorates Intestinal Candida albicans Infection by Modulating the Gut microbiota and Metabolites and Providing Intestinal Protection in Mice Front. Cell. Infect. Microbiol. 2021 11 743454 10.3389/fcimb.2021.743454 35071031 PMC8777027 · DOI
  56. [62]Gasaly N. de Vos P. Hermoso M.A. Impact of Bacterial Metabolites on Gut Barrier Function and Host Immunity: A Focus on Bacterial Metabolism and Its Relevance for Intestinal Inflammation Front. Immunol. 2021 12 658354 10.3389/fimmu.2021.658354 34122415 PMC8187770 · DOI
  57. [63]Vyhlidalova B. Krasulova K. Pecinkova P. Marcalikova A. Vrzal R. Zemankova L. Vanco J. Travnicek Z. Vondracek J. Karasova M. Gut Microbial Catabolites of Tryptophan Are Ligands and Agonists of the Aryl Hydrocarbon Receptor: A Detailed Characterization Int. J. Mol. Sci. 2020 21 2614 10.3390/ijms21072614 32283770 PMC7177849 · DOI
  58. [64]Goudot C. Coillard A. Villani A.C. Gueguen P. Cros A. Sarkizova S. Tang-Huau T.L. Bohec M. Baulande S. Hacohen N. Aryl Hydrocarbon Receptor Controls Monocyte Differentiation into Dendritic Cells versus Macrophages Immunity 2017 47 582 596.e6 10.1016/j.immuni.2017.08.016 28930664 · DOI · Paper page
  59. [65]Bessede A. Gargaro M. Pallotta M.T. Matino D. Servillo G. Brunacci C. Bicciato S. Mazza E.M. Macchiarulo A. Vacca C. Aryl hydrocarbon receptor control of a disease tolerance defence pathway Nature 2014 511 184 190 10.1038/nature13323 24930766 PMC4098076 · DOI
  60. [66]Kimura A. Naka T. Nakahama T. Chinen I. Masuda K. Nohara K. Fujii-Kuriyama Y. Kishimoto T. Aryl hydrocarbon receptor in combination with Stat1 regulates LPS-induced inflammatory responses J. Exp. Med. 2009 206 2027 2035 10.1084/jem.20090560 19703987 PMC2737163 · DOI
  61. [67]Grosskopf H. Walter K. Karkossa I. von Bergen M. Schubert K. Non-Genomic AhR-Signaling Modulates the Immune Response in Endotoxin-Activated Macrophages After Activation by the Environmental Stressor BaP Front. Immunol. 2021 12 620270 10.3389/fimmu.2021.620270 33868237 PMC8045971 · DOI
  62. [68]Masuda K. Kimura A. Hanieh H. Nguyen N.T. Nakahama T. Chinen I. Otoyo Y. Murotani T. Yamatodani A. Kishimoto T. Aryl hydrocarbon receptor negatively regulates LPS-induced IL-6 production through suppression of histamine production in macrophages Int. Immunol. 2011 23 637 645 10.1093/intimm/dxr072 21930594 · DOI
  63. [69]Walter K. Grosskopf H. Karkossa I. von Bergen M. Schubert K. Proteomic Characterization of the Cellular Effects of AhR Activation by Microbial Tryptophan Catabolites in Endotoxin-Activated Human Macrophages Int. J. Environ. Res. Public Health 2021 18 10336 10.3390/ijerph181910336 34639632 PMC8507890 · DOI
  64. [70]Zhu J. Luo L. Tian L. Yin S. Ma X. Cheng S. Tang W. Yu J. Ma W. Zhou X. Aryl Hydrocarbon Receptor Promotes IL-10 Expression in Inflammatory Macrophages Through Src-STAT3 Signaling Pathway Front. Immunol. 2018 9 2033 10.3389/fimmu.2018.02033 30283437 PMC6156150 · DOI
  65. [71]Campesato L.F. Budhu S. Tchaicha J. Weng C.H. Gigoux M. Cohen I.J. Redmond D. Mangarin L. Pourpe S. Liu C. Blockade of the AHR restricts a Treg-macrophage suppressive axis induced by L-Kynurenine Nat. Commun. 2020 11 4011 10.1038/s41467-020-17750-z 32782249 PMC7419300 · DOI
  66. [72]Opitz C.A. Litzenburger U.M. Sahm F. Ott M. Tritschler I. Trump S. Schumacher T. Jestaedt L. Schrenk D. Weller M. An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor Nature 2011 478 197 203 10.1038/nature10491 21976023 · DOI · Paper page
  67. [73]Lee K. Kwak J.H. Pyo S. Inhibition of LPS-induced inflammatory mediators by 3-hydroxyanthranilic acid in macrophages through suppression of PI3K/NF-kappaB signaling pathways Food Funct. 2016 7 3073 3082 10.1039/C6FO00187D 27264984 · DOI
  68. [74]Muller P.A. Matheis F. Mucida D. Gut macrophages: Key players in intestinal immunity and tissue physiology Curr. Opin. Immunol. 2020 62 54 61 10.1016/j.coi.2019.11.011 31841704 PMC7067652 · DOI
  69. [76]De Schepper S. Verheijden S. Aguilera-Lizarraga J. Viola M.F. Boesmans W. Stakenborg N. Voytyuk I. Schmidt I. Boeckx B. Dierckx de Casterle I. Self-Maintaining Gut Macrophages Are Essential for Intestinal Homeostasis Cell 2018 175 400 415.e13 10.1016/j.cell.2018.07.048 30173915 · DOI
  70. [77]Niess J.H. Brand S. Gu X. Landsman L. Jung S. McCormick B.A. Vyas J.M. Boes M. Ploegh H.L. Fox J.G. CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance Science 2005 307 254 258 10.1126/science.1102901 15653504 · DOI
  71. [78]Honda M. Surewaard B.G.J. Watanabe M. Hedrick C.C. Lee W.Y. Brown K. McCoy K.D. Kubes P. Perivascular localization of macrophages in the intestinal mucosa is regulated by Nr4a1 and the microbiome Nat. Commun. 2020 11 1329 10.1038/s41467-020-15068-4 32165624 PMC7067862 · DOI
  72. [79]Hadis U. Wahl B. Schulz O. Hardtke-Wolenski M. Schippers A. Wagner N. Muller W. Sparwasser T. Forster R. Pabst O. Intestinal tolerance requires gut homing and expansion of FoxP3+ regulatory T cells in the lamina propria Immunity 2011 34 237 246 10.1016/j.immuni.2011.01.016 21333554 · DOI
  73. [80]Riemschneider S. Kohlschmidt J. Fueldner C. Esser C. Hauschildt S. Lehmann J. Aryl hydrocarbon receptor activation by benzo(a)pyrene inhibits proliferation of myeloid precursor cells and alters the differentiation state as well as the functional phenotype of murine bone marrow-derived macrophages Toxicol. Lett. 2018 296 106 113 10.1016/j.toxlet.2018.07.050 30099064 · DOI
  74. [81]Platzer B. Richter S. Kneidinger D. Waltenberger D. Woisetschlager M. Strobl H. Aryl hydrocarbon receptor activation inhibits in vitro differentiation of human monocytes and Langerhans dendritic cells J. Immunol. 2009 183 66 74 10.4049/jimmunol.0802997 19535631 · DOI
  75. [83]Khattri R. Cox T. Yasayko S.A. Ramsdell F. An essential role for Scurfin in CD4+CD25+ T regulatory cells Nat. Immunol. 2003 4 337 342 10.1038/ni909 12612581 · DOI
  76. [84]Darrigues J. van Meerwijk J.P.M. Romagnoli P. Age-Dependent Changes in Regulatory T Lymphocyte Development and Function: A Mini-Review Gerontology 2018 64 28 35 10.1159/000478044 28704827 · DOI
  77. [85]Langhans B. Nischalke H.D. Kramer B. Dold L. Lutz P. Mohr R. Vogt A. Toma M. Eis-Hubinger A.M. Nattermann J. Role of regulatory T cells and checkpoint inhibition in hepatocellular carcinoma Cancer Immunol. Immunother. 2019 68 2055 2066 10.1007/s00262-019-02427-4 31724091 PMC11028391 · DOI
  78. [86]Russler-Germain E.V. Rengarajan S. Hsieh C.S. Antigen-specific regulatory T-cell responses to intestinal microbiota Mucosal Immunol. 2017 10 1375 1386 10.1038/mi.2017.65 28766556 PMC5939566 · DOI
  79. [87]Kim K.S. Hong S.W. Han D. Yi J. Jung J. Yang B.G. Lee J.Y. Lee M. Surh C.D. Dietary antigens limit mucosal immunity by inducing regulatory T cells in the small intestine Science 2016 351 858 863 10.1126/science.aac5560 26822607 · DOI
  80. [88]Apetoh L. Quintana F.J. Pot C. Joller N. Xiao S. Kumar D. Burns E.J. Sherr D.H. Weiner H.L. Kuchroo V.K. The aryl hydrocarbon receptor interacts with c-Maf to promote the differentiation of type 1 regulatory T cells induced by IL-27 Nat. Immunol. 2010 11 854 861 10.1038/ni.1912 20676095 PMC2940320 · DOI · Paper page
  81. [89]Gandhi R. Kumar D. Burns E.J. Nadeau M. Dake B. Laroni A. Kozoriz D. Weiner H.L. Quintana F.J. Activation of the aryl hydrocarbon receptor induces human type 1 regulatory T cell-like and Foxp3+ regulatory T cells Nat. Immunol. 2010 11 846 853 10.1038/ni.1915 20676092 PMC2929008 · DOI
  82. [90]Quintana F.J. Basso A.S. Iglesias A.H. Korn T. Farez M.F. Bettelli E. Caccamo M. Oukka M. Weiner H.L. Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor Nature 2008 453 65 71 10.1038/nature06880 18362915 · DOI · Paper page
  83. [91]Haspel J.A. Chettimada S. Shaik R.S. Chu J.H. Raby B.A. Cernadas M. Carey V. Process V. Hunninghake G.M. Ifedigbo E. Circadian rhythm reprogramming during lung inflammation Nat. Commun. 2014 5 4753 10.1038/ncomms5753 25208554 PMC4162491 · DOI
  84. [92]Mascanfroni I.D. Takenaka M.C. Yeste A. Patel B. Wu Y. Kenison J.E. Siddiqui S. Basso A.S. Otterbein L.E. Pardoll D.M. Metabolic control of type 1 regulatory T cell differentiation by AHR and HIF1-α Nat. Med. 2015 21 638 646 10.1038/nm.3868 26005855 PMC4476246 · DOI
  85. [93]Quintana F.J. Murugaiyan G. Farez M.F. Mitsdoerffer M. Tukpah A.M. Burns E.J. Weiner H.L. An endogenous aryl hydrocarbon receptor ligand acts on dendritic cells and T cells to suppress experimental autoimmune encephalomyelitis Proc. Natl. Acad. Sci. USA 2010 107 20768 20773 10.1073/pnas.1009201107 21068375 PMC2996442 · DOI
  86. [94]Abron J.D. Singh N.P. Mishra M.K. Price R.L. Nagarkatti M. Nagarkatti P.S. Singh U.P. An endogenous aryl hydrocarbon receptor ligand, ITE, induces regulatory T cells and ameliorates experimental colitis Am. J. Physiol. Gastrointest. Liver Physiol. 2018 315 G220 G230 10.1152/ajpgi.00413.2017 29672155 PMC6139639 · DOI
  87. [95]Hao N. Whitelaw M.L. The emerging roles of AhR in physiology and immunity Biochem. Pharmacol. 2013 86 561 570 10.1016/j.bcp.2013.07.004 23856287 · DOI
  88. [96]Bruhs A. Haarmann-Stemmann T. Frauenstein K. Krutmann J. Schwarz T. Schwarz A. Activation of the arylhydrocarbon receptor causes immunosuppression primarily by modulating dendritic cells J. Investig. Dermatol. 2015 135 435 444 10.1038/jid.2014.419 25251932 · DOI
  89. [97]Huang Z. Jiang Y. Yang Y. Shao J. Sun X. Chen J. Dong L. Zhang J. 3,3′-Diindolylmethane alleviates oxazolone-induced colitis through Th2/Th17 suppression and Treg induction Mol. Immunol. 2013 53 335 344 10.1016/j.molimm.2012.09.007 23085552 · DOI
  90. [98]Ehrlich A.K. Pennington J.M. Wang X. Rohlman D. Punj S. Lohr C.V. Newman M.T. Kolluri S.K. Kerkvliet N.I. Activation of the Aryl Hydrocarbon Receptor by 10-Cl-BBQ Prevents Insulitis and Effector T Cell Development Independently of Foxp3+ Regulatory T Cells in Nonobese Diabetic Mice J. Immunol. 2016 196 264 273 10.4049/jimmunol.1501789 26573835 PMC4684970 · DOI
  91. [99]Ye J. Qiu J. Bostick J.W. Ueda A. Schjerven H. Li S. Jobin C. Chen Z.E. Zhou L. The Aryl Hydrocarbon Receptor Preferentially Marks and Promotes Gut Regulatory T Cells Cell Rep. 2017 21 2277 2290 10.1016/j.celrep.2017.10.114 29166616 PMC5880207 · DOI
  92. [100]Mezrich J.D. Fechner J.H. Zhang X. Johnson B.P. Burlingham W.J. Bradfield C.A. An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells J. Immunol. 2010 185 3190 3198 10.4049/jimmunol.0903670 20720200 PMC2952546 · DOI
  93. [101]Goettel J.A. Gandhi R. Kenison J.E. Yeste A. Murugaiyan G. Sambanthamoorthy S. Griffith A.E. Patel B. Shouval D.S. Weiner H.L. AHR Activation Is Protective against Colitis Driven by T Cells in Humanized Mice Cell Rep. 2016 17 1318 1329 10.1016/j.celrep.2016.09.082 27783946 PMC5106873 · DOI
  94. [102]Tashita C. Hoshi M. Hirata A. Nakamoto K. Ando T. Hattori T. Yamamoto Y. Tezuka H. Tomita H. Hara A. Kynurenine plays an immunosuppressive role in 2,4,6-trinitrobenzene sulfate-induced colitis in mice World J. Gastroenterol. 2020 26 918 932 10.3748/wjg.v26.i9.918 32206003 PMC7081011 · DOI
  95. [103]Gargaro M. Vacca C. Massari S. Scalisi G. Manni G. Mondanelli G. Mazza E.M.C. Bicciato S. Pallotta M.T. Orabona C. Engagement of Nuclear Coactivator 7 by 3-Hydroxyanthranilic Acid Enhances Activation of Aryl Hydrocarbon Receptor in Immunoregulatory Dendritic Cells Front. Immunol. 2019 10 1973 10.3389/fimmu.2019.01973 31481962 PMC6710348 · DOI
  96. [104]Roncarolo M.G. Gregori S. Battaglia M. Bacchetta R. Fleischhauer K. Levings M.K. Interleukin-10-secreting type 1 regulatory T cells in rodents and humans Immunol. Rev. 2006 212 28 50 10.1111/j.0105-2896.2006.00420.x 16903904 · DOI
  97. [105]Saraiva M. O’Garra A. The regulation of IL-10 production by immune cells Nat. Rev. Immunol. 2010 10 170 181 10.1038/nri2711 20154735 · DOI
  98. [106]Vuddamalay Y. Attia M. Vicente R. Pomie C. Enault G. Leobon B. Joffre O. Romagnoli P. van Meerwijk J.P. Mouse and human CD8+ CD28low regulatory T lymphocytes differentiate in the thymus Immunology 2016 148 187 196 10.1111/imm.12600 26924728 PMC4863570 · DOI
  99. [107]Ehrlich A.K. Pennington J.M. Tilton S. Wang X. Marshall N.B. Rohlman D. Funatake C. Punj S. O’Donnell E. Yu Z. AhR activation increases IL-2 production by alloreactive CD4+ T cells initiating the differentiation of mucosal-homing Tim3+ Lag3+ Tr1 cells Eur. J. Immunol. 2017 47 1989 2001 10.1002/eji.201747121 28833046 PMC5927372 · DOI
  100. [108]Iperi C. Bordron A. Dueymes M. Pers J.O. Jamin C. Metabolic Program of Regulatory B Lymphocytes and Influence in the Control of Malignant and Autoimmune Situations Front. Immunol. 2021 12 735463 10.3389/fimmu.2021.735463 34650560 PMC8505885 · DOI
  101. [109]Shen P. Roch T. Lampropoulou V. O’Connor R.A. Stervbo U. Hilgenberg E. Ries S. Dang V.D. Jaimes Y. Daridon C. IL-35-producing B cells are critical regulators of immunity during autoimmune and infectious diseases Nature 2014 507 366 370 10.1038/nature12979 24572363 PMC4260166 · DOI · Paper page
  102. [110]Nishimura S. Manabe I. Takaki S. Nagasaki M. Otsu M. Yamashita H. Sugita J. Yoshimura K. Eto K. Komuro I. Adipose Natural Regulatory B Cells Negatively Control Adipose Tissue Inflammation Cell Metab. 2013 18 759 766 10.1016/j.cmet.2013.09.017 24209772 · DOI · Paper page
  103. [111]Yanaba K. Bouaziz J.D. Haas K.M. Poe J.C. Fujimoto M. Tedder T.F. A regulatory B cell subset with a unique CD1dhiCD5+ phenotype controls T cell-dependent inflammatory responses Immunity 2008 28 639 650 10.1016/j.immuni.2008.03.017 18482568 · DOI
  104. [112]Su X. Zhang M. Qi H. Gao Y. Yang Y. Yun H. Zhang Q. Yang X. Zhang Y. He J. Gut microbiota-derived metabolite 3-idoleacetic acid together with LPS induces IL-35+ B cell generation Microbiome 2022 10 13 10.1186/s40168-021-01205-8 35074011 PMC8785567 · DOI
  105. [113]Rosser E.C. Mauri C. The emerging field of regulatory B cell immunometabolism Cell Metab. 2021 33 1088 1097 10.1016/j.cmet.2021.05.008 34077716 · DOI
  106. [114]Mauri C. Bosma A. Immune regulatory function of B cells Annu. Rev. Immunol. 2012 30 221 241 10.1146/annurev-immunol-020711-074934 22224776 · DOI
  107. [115]Wang R.X. Yu C.R. Dambuza I.M. Mahdi R.M. Dolinska M.B. Sergeev Y.V. Wingfield P.T. Kim S.H. Egwuagu C.E. Interleukin-35 induces regulatory B cells that suppress autoimmune disease Nat. Med. 2014 20 633 641 10.1038/nm.3554 24743305 PMC4048323 · DOI
  108. [116]Zhang J. Lin Y. Li C. Zhang X. Cheng L. Dai L. Wang Y. Wang F. Shi G. Li Y. IL-35 Decelerates the Inflammatory Process by Regulating Inflammatory Cytokine Secretion and M1/M2 Macrophage Ratio in Psoriasis J. Immunol. 2016 197 2131 2144 10.4049/jimmunol.1600446 27527600 · DOI
  109. [117]Sawant D.V. Yano H. Chikina M. Zhang Q. Liao M. Liu C. Callahan D.J. Sun Z. Sun T. Tabib T. Adaptive plasticity of IL-10+ and IL-35+ Treg cells cooperatively promotes tumor T cell exhaustion Nat. Immunol. 2019 20 724 735 10.1038/s41590-019-0346-9 30936494 PMC6531353 · DOI
  110. [118]Chen C. Xu H. Peng Y. Luo H. Huang G.X. Wu X.J. Dai Y.C. Luo H.L. Zhang J.A. Zheng B.Y. Elevation in the counts of IL-35-producing B cells infiltrating into lung tissue in mycobacterial infection is associated with the downregulation of Th1/Th17 and upregulation of Foxp3+Treg Sci. Rep. 2020 10 13212 10.1038/s41598-020-69984-y 32764544 PMC7411070 · DOI
  111. [119]Vignali D.A. Kuchroo V.K. IL-12 family cytokines: Immunological playmakers Nat. Immunol. 2012 13 722 728 10.1038/ni.2366 22814351 PMC4158817 · DOI
  112. [120]Dambuza I.M. He C. Choi J.K. Yu C.R. Wang R. Mattapallil M.J. Wingfield P.T. Caspi R.R. Egwuagu C.E. IL-12p35 induces expansion of IL-10 and IL-35-expressing regulatory B cells and ameliorates autoimmune disease Nat. Commun. 2017 8 719 10.1038/s41467-017-00838-4 28959012 PMC5620058 · DOI
  113. [121]Fagarasan S. Muramatsu M. Suzuki K. Nagaoka H. Hiai H. Honjo T. Critical roles of activation-induced cytidine deaminase in the homeostasis of gut flora Science 2002 298 1424 1427 10.1126/science.1077336 12434060 · DOI
  114. [122]Lundell A.C. Bjornsson V. Ljung A. Ceder M. Johansen S. Lindhagen G. Tornhage C.J. Adlerberth I. Wold A.E. Rudin A. Infant B cell memory differentiation and early gut bacterial colonization J. Immunol. 2012 188 4315 4322 10.4049/jimmunol.1103223 22490441 · DOI
  115. [123]Wang L. Zhu S. Xu G. Feng J. Han T. Zhao F. She Y.L. Liu S. Ye L. Zhu Y. Gene Expression and Antiviral Activity of Interleukin-35 in Response to Influenza A Virus Infection J. Biol. Chem. 2016 291 16863 16876 10.1074/jbc.M115.693101 27307042 PMC4974397 · DOI
  116. [124]Venkatesh M. Mukherjee S. Wang H. Li H. Sun K. Benechet A.P. Qiu Z. Maher L. Redinbo M.R. Phillips R.S. Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4 Immunity 2014 41 296 310 10.1016/j.immuni.2014.06.014 25065623 PMC4142105 · DOI · Paper page
  117. [125]Dudakov J.A. Hanash A.M. van den Brink M.R. Interleukin-22: Immunobiology and pathology Annu. Rev. Immunol. 2015 33 747 785 10.1146/annurev-immunol-032414-112123 25706098 PMC4407497 · DOI
  118. [126]Spits H. Artis D. Colonna M. Diefenbach A. Di Santo J.P. Eberl G. Koyasu S. Locksley R.M. McKenzie A.N. Mebius R.E. Innate lymphoid cells—A proposal for uniform nomenclature Nat. Rev. Immunol. 2013 13 145 149 10.1038/nri3365 23348417 · DOI
  119. [127]Li S. Bostick J.W. Zhou L. Regulation of Innate Lymphoid Cells by Aryl Hydrocarbon Receptor Front. Immunol. 2017 8 1909 10.3389/fimmu.2017.01909 29354125 PMC5760495 · DOI
  120. [128]Liang S.C. Tan X.Y. Luxenberg D.P. Karim R. Dunussi-Joannopoulos K. Collins M. Fouser L.A. Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides J. Exp. Med. 2006 203 2271 2279 10.1084/jem.20061308 16982811 PMC2118116 · DOI · Paper page
  121. [129]Gutierrez-Vazquez C. Quintana F.J. Regulation of the Immune Response by the Aryl Hydrocarbon Receptor Immunity 2018 48 19 33 10.1016/j.immuni.2017.12.012 29343438 PMC5777317 · DOI · Paper page
  122. [131]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 92 104 10.1016/j.immuni.2011.11.011 22177117 PMC3268875 · DOI
  123. [132]Gomez de Aguero M. Ganal-Vonarburg S.C. Fuhrer T. Rupp S. Uchimura Y. Li H. Steinert A. Heikenwalder M. Hapfelmeier S. Sauer U. The maternal microbiota drives early postnatal innate immune development Science 2016 351 1296 1302 10.1126/science.aad2571 26989247 · DOI · Paper page
  124. [133]Ebihara T. Song C. Ryu S.H. Plougastel-Douglas B. Yang L. Levanon D. Groner Y. Bern M.D. Stappenbeck T.S. Colonna M. Runx3 specifies lineage commitment of innate lymphoid cells Nat. Immunol. 2015 16 1124 1133 10.1038/ni.3272 26414766 PMC4618046 · DOI
  125. [134]Li S. Heller J.J. Bostick J.W. Lee A. Schjerven H. Kastner P. Chan S. Chen Z.E. Zhou L. Ikaros Inhibits Group 3 Innate Lymphoid Cell Development and Function by Suppressing the Aryl Hydrocarbon Receptor Pathway Immunity 2016 45 185 197 10.1016/j.immuni.2016.06.027 27438771 PMC4959810 · DOI
  126. [135]Kiss E.A. Vonarbourg C. Kopfmann S. Hobeika E. Finke D. Esser C. Diefenbach A. Natural aryl hydrocarbon receptor ligands control organogenesis of intestinal lymphoid follicles Science 2011 334 1561 1565 10.1126/science.1214914 22033518 · DOI · Paper page
  127. [136]Li S. Bostick J.W. Ye J. Qiu J. Zhang B. Urban J.F. Jr. Avram D. Zhou L. Aryl Hydrocarbon Receptor Signaling Cell Intrinsically Inhibits Intestinal Group 2 Innate Lymphoid Cell Function Immunity 2018 49 915 928.e5 10.1016/j.immuni.2018.09.015 30446384 PMC6249058 · DOI
  128. [137]Chen W. Pu A. Sheng B. Zhang Z. Li L. Liu Z. Wang Q. Li X. Ma Y. Yu M. Aryl hydrocarbon receptor activation modulates CD8αα+TCRαβ+ IELs and suppression of colitis manifestations in mice Biomed. Pharmacother. 2017 87 127 134 10.1016/j.biopha.2016.12.061 28049094 · DOI
  129. [138]Wang J. Simonavicius N. Wu X. Swaminath G. Reagan J. Tian H. Ling L. Kynurenic acid as a ligand for orphan G protein-coupled receptor GPR35 J. Biol. Chem. 2006 281 22021 22028 10.1074/jbc.M603503200 16754668 · DOI
  130. [139]Frumento G. Rotondo R. Tonetti M. Damonte G. Benatti U. Ferrara G.B. Tryptophan-derived catabolites are responsible for inhibition of T and natural killer cell proliferation induced by indoleamine 2,3-dioxygenase J. Exp. Med. 2002 196 459 468 10.1084/jem.20020121 12186838 PMC2196046 · DOI · Paper page
  131. [140]Fallarino F. Grohmann U. Vacca C. Bianchi R. Orabona C. Spreca A. Fioretti M.C. Puccetti P. T cell apoptosis by tryptophan catabolism Cell Death Differ. 2002 9 1069 1077 10.1038/sj.cdd.4401073 12232795 · DOI · Paper page
  132. [141]Orabona C. Puccetti P. Vacca C. Bicciato S. Luchini A. Fallarino F. Bianchi R. Velardi E. Perruccio K. Velardi A. Toward the identification of a tolerogenic signature in IDO-competent dendritic cells Blood 2006 107 2846 2854 10.1182/blood-2005-10-4077 16339401 · DOI
  133. [142]Lanz T.V. Becker S. Mohapatra S.R. Opitz C.A. Wick W. Platten M. Suppression of Th1 differentiation by tryptophan supplementation in vivo Amino Acids 2017 49 1169 1175 10.1007/s00726-017-2415-4 28421297 · DOI
  134. [144]Clarke G. McKernan D.P. Gaszner G. Quigley E.M. Cryan J.F. Dinan T.G. A Distinct Profile of Tryptophan Metabolism along the Kynurenine Pathway Downstream of Toll-Like Receptor Activation in Irritable Bowel Syndrome Front. Pharmacol. 2012 3 90 10.3389/fphar.2012.00090 22661947 PMC3357104 · DOI
  135. [145]Whitfield-Cargile C.M. Cohen N.D. Chapkin R.S. Weeks B.R. Davidson L.A. Goldsby J.S. Hunt C.L. Steinmeyer S.H. Menon R. Suchodolski J.S. The microbiota-derived metabolite indole decreases mucosal inflammation and injury in a murine model of NSAID enteropathy Gut Microbes 2016 7 246 261 10.1080/19490976.2016.1156827 27007819 PMC4939928 · DOI
  136. [146]Sofia M.A. Ciorba M.A. Meckel K. Lim C.K. Guillemin G.J. Weber C.R. Bissonnette M. Pekow J.R. Tryptophan Metabolism through the Kynurenine Pathway is Associated with Endoscopic Inflammation in Ulcerative Colitis Inflamm. Bowel Dis. 2018 24 1471 1480 10.1093/ibd/izy103 29796641 PMC6196764 · DOI
  137. [147]Ramos F.J. Kaeberlein M. Ageing: A healthy diet for stem cells Nature 2012 486 477 478 10.1038/486477a 22739309 · DOI
  138. [148]Ala M. Tryptophan metabolites modulate inflammatory bowel disease and colorectal cancer by affecting immune system Int. Rev. Immunol. 2022 41 326 345 10.1080/08830185.2021.1954638 34289794 · DOI
  139. [151]Sivaprakasam S. Bhutia Y.D. Ramachandran S. Ganapathy V. Cell-Surface and Nuclear Receptors in the Colon as Targets for Bacterial Metabolites and Its Relevance to Colon Health Nutrients 2017 9 856 10.3390/nu9080856 PMC5579649 28796169 · DOI
  140. [152]Dai G. Chen X. He Y. The Gut Microbiota Activates AhR Through the Tryptophan Metabolite Kyn to Mediate Renal Cell Carcinoma Metastasis Front. Nutr. 2021 8 712327 10.3389/fnut.2021.712327 34458309 PMC8384964 · DOI
  141. [153]Park E.M. Chelvanambi M. Bhutiani N. Kroemer G. Zitvogel L. Wargo J.A. Targeting the gut and tumor microbiota in cancer Nat. Med. 2022 28 690 703 10.1038/s41591-022-01779-2 35440726 · DOI · Paper page
  142. [154]Trezeguet V. Fatrouni H. Merched A.J. Immuno-Metabolic Modulation of Liver Oncogenesis by the Tryptophan Metabolism Cells 2021 10 3469 10.3390/cells10123469 34943977 PMC8700200 · DOI
  143. [155]Hezaveh K. Shinde R.S. Klotgen A. Halaby M.J. Lamorte S. Ciudad M.T. Quevedo R. Neufeld L. Liu Z.Q. Jin R. Tryptophan-derived microbial metabolites activate the aryl hydrocarbon receptor in tumor-associated macrophages to suppress anti-tumor immunity Immunity 2022 55 324 340.e8 10.1016/j.immuni.2022.01.006 35139353 PMC8888129 · DOI · Paper page
  144. [156]Mallmann N.H. Lima E.S. Lalwani P. Dysregulation of Tryptophan Catabolism in Metabolic Syndrome Metab. Syndr. Relat. Disord. 2018 16 135 142 10.1089/met.2017.0097 29406815 · DOI
  145. [157]De Mello V.D. Paananen J. Lindstrom J. Lankinen M.A. Shi L. Kuusisto J. Pihlajamaki J. Auriola S. Lehtonen M. Rolandsson O. Indolepropionic acid and novel lipid metabolites are associated with a lower risk of type 2 diabetes in the Finnish Diabetes Prevention Study Sci. Rep. 2017 7 46337 10.1038/srep46337 28397877 PMC5387722 · DOI
  146. [158]Qi Q. Li J. Yu B. Moon J.Y. Chai J.C. Merino J. Hu J. Ruiz-Canela M. Rebholz C. Wang Z. Host and gut microbial tryptophan metabolism and type 2 diabetes: An integrative analysis of host genetics, diet, gut microbiome and circulating metabolites in cohort studies Gut 2022 71 1095 1105 10.1136/gutjnl-2021-324053 34127525 PMC8697256 · DOI
  147. [159]Rothhammer V. Mascanfroni I.D. Bunse L. Takenaka M.C. Kenison J.E. Mayo L. Chao C.C. Patel B. Yan R. Blain M. Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor Nat. Med. 2016 22 586 597 10.1038/nm.4106 27158906 PMC4899206 · DOI · Paper page
  148. [160]Rosas H.D. Doros G. Bhasin S. Thomas B. Gevorkian S. Malarick K. Matson W. Hersch S.M. A systems-level “misunderstanding”: The plasma metabolome in Huntington’s disease Ann. Clin. Transl. Neurol. 2015 2 756 768 10.1002/acn3.214 26273688 PMC4531058 · DOI
  149. [162]Schiering C. Wincent E. Metidji A. Iseppon A. Li Y. Potocnik A.J. Omenetti S. Henderson C.J. Wolf C.R. Nebert D.W. Feedback control of AHR signalling regulates intestinal immunity Nature 2017 542 242 245 10.1038/nature21080 28146477 PMC5302159 · DOI
  150. [163]Ye X. Li H. Anjum K. Zhong X. Miao S. Zheng G. Liu W. Li L. Dual Role of Indoles Derived from Intestinal Microbiota on Human Health Front. Immunol. 2022 13 903526 10.3389/fimmu.2022.903526 35784338 PMC9248744 · DOI
  151. [164]Paeslack N. Mimmler M. Becker S. Gao Z. Khuu M.P. Mann A. Malinarich F. Regen T. Reinhardt C. Microbiota-derived tryptophan metabolites in vascular inflammation and cardiovascular disease Amino Acids 2022 10.1007/s00726-022-03161-5 35451695 PMC9641817 · DOI
  152. [165]Teunis C. Nieuwdorp M. Hanssen N. Interactions between Tryptophan Metabolism, the Gut Microbiome and the Immune System as Potential Drivers of Non-Alcoholic Fatty Liver Disease (NAFLD) and Metabolic Diseases Metabolites 2022 12 514 10.3390/metabo12060514 35736447 PMC9227929 · DOI
  153. [166]Sehgal R. Ilha M. Vaittinen M. Kaminska D. Mannisto V. Karja V. Tuomainen M. Hanhineva K. Romeo S. Pajukanta P. Indole-3-Propionic Acid, a Gut-Derived Tryptophan Metabolite, Associates with Hepatic Fibrosis Nutrients 2021 13 3509 10.3390/nu13103509 34684510 PMC8538297 · DOI
  154. [167]Gargaro M. Manni G. Scalisi G. Puccetti P. Fallarino F. Tryptophan Metabolites at the Crossroad of Immune-Cell Interaction via the Aryl Hydrocarbon Receptor: Implications for Tumor Immunotherapy Int. J. Mol. Sci. 2021 22 4644 10.3390/ijms22094644 33924971 PMC8125364 · DOI
  155. [169]Zhang X. Liu X. Zhou W. Du Q. Yang M. Ding Y. Hu R. Blockade of IDO-Kynurenine-AhR Axis Ameliorated Colitis-Associated Colon Cancer via Inhibiting Immune Tolerance Cell. Mol. Gastroenterol. Hepatol. 2021 12 1179 1199 10.1016/j.jcmgh.2021.05.018 34087454 PMC8445903 · DOI
  156. [173]Carrillo-Salinas F.J. Anastasiou M. Ngwenyama N. Kaur K. Tai A. Smolgovsky S.A. Jetton D. Aronovitz M. Alcaide P. Gut dysbiosis induced by cardiac pressure overload enhances adverse cardiac remodeling in a T cell-dependent manner Gut Microbes 2020 12 1823801 10.1080/19490976.2020.1823801 33103561 PMC7588211 · DOI
  157. [174]Gaspar R. Halmi D. Demjan V. Berkecz R. Pipicz M. Csont T. Kynurenine Pathway Metabolites as Potential Clinical Biomarkers in Coronary Artery Disease Front. Immunol. 2021 12 768560 10.3389/fimmu.2021.768560 35211110 PMC8861075 · DOI
  158. [175]Zhang Z. Mu X. Cao Q. Shi Y. Hu X. Zheng H. Honeybee gut Lactobacillus modulates host learning and memory behaviors via regulating tryptophan metabolism Nat. Commun. 2022 13 2037 10.1038/s41467-022-29760-0 35440638 PMC9018956 · DOI
  159. [176]Martin R. Langella P. Emerging Health Concepts in the Probiotics Field: Streamlining the Definitions Front. Microbiol. 2019 10 1047 10.3389/fmicb.2019.01047 31164874 PMC6536656 · DOI · Paper page

Cited by

Sorted by citations

Authors
Su, X., Gao, Y., & Yang, R.
Affiliations
  • Translational Medicine Institute, Affiliated Tianjin Union Medical Center, Nankai University, Tianjin 300071, China
  • Nankai University (CN)
Corresponding author
Yang, Rongcun
ORCID
Yang, Rongcun
Venue
Cells
Publisher
MDPI AG
Published
2022-07-25
Volume
11
Issue
15
Pages
2296
ISSN
2073-4409 (ISSN-L)
DOI
10.3390/cells11152296
PMC
PMC9330295
OpenAlex
W4287838926
Cited by
424
References
17
Citations by year
2026: 132 · 2025: 123 · 2024: 112 · 2023: 47 · 2022: 10
FWCI
7.65
Type
journal article
Language
en
Open access
Licence
Locations
  • Cells (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
NSFC (91842302, 81970488, 91029736, 9162910, 91442111, 31570114)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Nutrition and Physiology
Keywords
tryptophan metabolites, gut microbiota, kynurenine pathway, indole-3-acetic acid, kynurenine, regulatory T cells, regulatory B cells, anti-inflammatory macrophages, systemic immunity, inflammatory bowel disease, cancer immunotherapy, obesity, metabolic syndrome, liver fibrosis, cardiovascular disease
MeSH terms
Gastrointestinal Microbiome, Homeostasis, Immunity, Innate, Immunotherapy, Indoles, Kynurenine, Lymphocytes, Tryptophan

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