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image of Luohuazizhu Granules Alleviate Symptoms of Ulcerative Colitis via Changes in Bile Acid Metabolism and Gut Microbiota

Abstract

Introduction

Luohuazizhu granules (LHZZG) are made of Hook. (CN), which is used to treat ulcerative colitis (UC). The anti-inflammatory effects of CN on UC have been previously reported. However, the biological effects of LHZZG on bile acids (BAs) in UC and the underlying mechanisms remain unexplored.

Methods

Integrated metabolomics were used to explore the regulatory mechanisms of LHZZG for BA metabolism in UC mice. Both 16S rDNA sequencing and flow cytometry analyses were combined to comprehensively assess gut microbiota (GM) and immune responses.

Results

Twenty-five differential biomarkers were identified in the untargeted metabolomic analysis, most of which were correlated with BA metabolism. UC signs were significantly alleviated after LHZZG treatment. The targeted metabolomics analysis revealed BA metabolic disorders to be significantly improved following LHZZG treatment. Additionally, the imbalances in the GM and immune cells related to BA metabolism were restored.

Discussion

This study not only confirmed significant dose-dependent protective effects of LHZZG in UC mice, but also performed the first investigation into the underlying mechanisms related to BA metabolism and immune function. Nevertheless, the limitations precluded a definitive mechanistic explanation for the observed changes. Consequently, in-depth mechanistic investigations will be prioritized in subsequent research to experimentally validate this hypothesis.

Conclusion

BAs could serve as biomarkers for evaluating the therapeutic effects of LHZZG on UC. This study has provided the first detailed explanation of the mechanism underlying the effects of LHZZG from a BA metabolic perspective, providing a foundation for their clinical application in UC.

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2025-07-02
2025-10-30
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References

  1. Gajendran M. Loganathan P. Jimenez G. Catinella A.P. Ng N. Umapathy C. Ziade N. Hashash J.G. A comprehensive review and update on ulcerative colitis. Dis. Mon. 2019 65 12 100851 10.1016/j.disamonth.2019.02.004 30837080
    [Google Scholar]
  2. Du L. Ha C. Epidemiology and pathogenesis of ulcerative colitis. Gastroenterol. Clin. North Am. 2020 49 4 643 654 10.1016/j.gtc.2020.07.005 33121686
    [Google Scholar]
  3. Park J. Cheon J.H. Updates on conventional therapies for inflammatory bowel diseases: 5-aminosalicylates, corticosteroids, immunomodulators, and anti-TNF-α. Korean J. Intern. Med. (Korean. Assoc. Intern. Med.) 2022 37 5 895 905 10.3904/kjim.2022.132 35882566
    [Google Scholar]
  4. Frias Gomes C. Chapman T.P. Satsangi J. De-escalation of medical therapy in inflammatory bowel disease. Curr. Opin. Pharmacol. 2020 55 73 81 10.1016/j.coph.2020.09.014 33160250
    [Google Scholar]
  5. Kayama H. Okumura R. Takeda K. Interaction between the microbiota, epithelia, and immune cells in the intestine. Annu. Rev. Immunol. 2020 38 1 23 48 10.1146/annurev‑immunol‑070119‑115104 32340570
    [Google Scholar]
  6. O’Hara A.M. Shanahan F. The gut flora as a forgotten organ. EMBO Rep. 2006 7 7 688 693 10.1038/sj.embor.7400731 16819463
    [Google Scholar]
  7. 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
    [Google Scholar]
  8. Zhu J. Yin J. Chen J. Hu M. Lu W. Wang H. Zhang H. Chen W. Integrative analysis with microbial modelling and machine learning uncovers potential alleviators for ulcerative colitis. Gut Microbes 2024 16 1 2336877 10.1080/19490976.2024.2336877 38563656
    [Google Scholar]
  9. Haneishi Y. Furuya Y. Hasegawa M. Picarelli A. Rossi M. Miyamoto J. Inflammatory bowel diseases and gut microbiota. Int. J. Mol. Sci. 2023 24 4 3817 10.3390/ijms24043817 36835245
    [Google Scholar]
  10. Franzosa E.A. Sirota-Madi A. Avila-Pacheco J. Fornelos N. Haiser H.J. Reinker S. Vatanen T. Hall A.B. Mallick H. McIver L.J. Sauk J.S. Wilson R.G. Stevens B.W. Scott J.M. Pierce K. Deik A.A. Bullock K. Imhann F. Porter J.A. Zhernakova A. Fu J. Weersma R.K. Wijmenga C. Clish C.B. Vlamakis H. Huttenhower C. Xavier R.J. Gut microbiome structure and metabolic activity in inflammatory bowel disease. Nat. Microbiol. 2018 4 2 293 305 10.1038/s41564‑018‑0306‑4 30531976
    [Google Scholar]
  11. Thomas J.P. Modos D. Rushbrook S.M. Powell N. Korcsmaros T. The emerging role of bile acids in the pathogenesis of inflammatory bowel disease. Front. Immunol. 2022 13 829525 829525 10.3389/fimmu.2022.829525 35185922
    [Google Scholar]
  12. Yang Z.H. Liu F. Zhu X.R. Suo F.Y. Jia Z. Yao S.K. Altered profiles of fecal bile acids correlate with gut microbiota and inflammatory responses in patients with ulcerative colitis. World J. Gastroenterol. 2021 27 24 3609 3629 10.3748/wjg.v27.i24.3609 34239273
    [Google Scholar]
  13. Su X. Gao Y. Yang R. Gut microbiota derived bile acid metabolites maintain the homeostasis of gut and systemic immunity. Front. Immunol. 2023 14 1127743 10.3389/fimmu.2023.1127743 37256134
    [Google Scholar]
  14. Mowat A.M. Agace W.W. Regional specialization within the intestinal immune system. Nat. Rev. Immunol. 2014 14 10 667 685 10.1038/nri3738 25234148
    [Google Scholar]
  15. Campbell C. McKenney P.T. Konstantinovsky D. Isaeva O.I. Schizas M. Verter J. Mai C. Jin W.B. Guo C.J. Violante S. Ramos R.J. Cross J.R. Kadaveru K. Hambor J. Rudensky A.Y. Bacterial metabolism of bile acids promotes generation of peripheral regulatory T cells. Nature 2020 581 7809 475 479 10.1038/s41586‑020‑2193‑0 32461639
    [Google Scholar]
  16. Zhou M. Liu X. He J. Xu X. Ju C. Luo S. Lu X. Du P. Chen Y. High-fructose corn syrup aggravates colitis via microbiota dysbiosis-mediated Th17/Treg imbalance. Clin. Sci. (Lond.) 2023 137 20 1619 1635 10.1042/CS20230788 37818653
    [Google Scholar]
  17. Saez A. Gomez-Bris R. Herrero-Fernandez B. Mingorance C. Rius C. Gonzalez-Granado J.M. Innate lymphoid cells in intestinal homeostasis and inflammatory bowel disease. Int. J. Mol. Sci. 2021 22 14 7618 10.3390/ijms22147618 34299236
    [Google Scholar]
  18. Jia Q. Zhang H. Hu P. Yang Y. Yang Y. Kang X. Li X. Wu Y. Xiao J. Zhou B. Chemical profiling and quality evaluation of callicarpa nudiflora from different regions in China by UPLC‐QTOF‐MS fingerprint. Chem. Biodivers. 2022 19 10 e202200444 10.1002/cbdv.202200444 36066484
    [Google Scholar]
  19. Yang Y. Li Z.Y. Shao J.J. Wang G. Wen R. Tian J.Z. Hou L. Callicarpa nudiflora Hook. & Arn.: A comprehensive review of its phytochemistry and pharmacology. J. Ethnopharmacol. 2021 264 113123 10.1016/j.jep.2020.113123 32783986
    [Google Scholar]
  20. Nong K. Qin X. Liu Z. Wang Z. Wu Y. Zhang B. Chen W. Fang X. Liu Y. Wang X. Zhang H. Potential effects and mechanism of flavonoids extract of Callicarpa nudiflora Hook on DSS-induced colitis in mice. Phytomedicine 2024 128 155523 10.1016/j.phymed.2024.155523 38489893
    [Google Scholar]
  21. Qin X. Nong K. Liu Z. Fang X. Zhang B. Chen W. Wang Z. Wu Y. Shi H. Wang X. Zhang H. Regulation of the intestinal flora using polysaccharides from Callicarpa nudiflora Hook to alleviate ulcerative colitis and the molecular mechanisms involved. Int. J. Biol. Macromol. 2024 258 Pt 1 128887 10.1016/j.ijbiomac.2023.128887 38118262
    [Google Scholar]
  22. Liang Y. Lin C. Zhong W. Clinical study on Luohua Zizhu Granules combined with octreotide in treatment of upper gastrointestinal hemorrhage due to cirrhosis. 2020 35 4 756 759 [in Chinese]. 10.7501/j.issn.1674‑5515.2020.04.033
    [Google Scholar]
  23. Guo C. Kang X. Cao F. Yang J. Xu Y. Liu X. Li Y. Ma X. Fu X. Network Pharmacology and molecular docking on the molecular mechanism of Luo-hua-zi-zhu (LHZZ) Granule in the prevention and treatment of bowel precancerous lesions. Front. Pharmacol. 2021 12 629021 10.3389/fphar.2021.629021 33692692
    [Google Scholar]
  24. Bujak R. Struck-Lewicka W. Markuszewski M.J. Kaliszan R. Metabolomics for laboratory diagnostics. J. Pharm. Biomed. Anal. 2015 113 108 120 10.1016/j.jpba.2014.12.017 25577715
    [Google Scholar]
  25. Cooper H.S. Murthy S.N. Shah R.S. Sedergran D.J. Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab. Invest. 1993 69 2 238 249 8350599
    [Google Scholar]
  26. Erben U. Loddenkemper C. Doerfel K. Spieckermann S. Haller D. Heimesaat M.M. Zeitz M. Siegmund B. Kühl A.A. A guide to histomorphological evaluation of intestinal inflammation in mouse models. Int. J. Clin. Exp. Pathol. 2014 7 8 4557 4576 25197329
    [Google Scholar]
  27. Li M. Gao Y. Yue X. Zhang B. Zhou H. Yuan C. Wu T. Integrated metabolomics and network pharmacology approach to reveal immunomodulatory mechanisms of Yupingfeng granules. J. Pharm. Biomed. Anal. 2021 194 113660 10.1016/j.jpba.2020.113660 33261954
    [Google Scholar]
  28. Huang L. Liu M. Shen L. Chen D. Wu T. Gao Y. Polysaccharides from Yupingfeng granules ameliorated cyclophosphamide-induced immune injury by protecting intestinal barrier. Int. Immunopharmacol. 2025 146 113866 10.1016/j.intimp.2024.113866 39709910
    [Google Scholar]
  29. Caprilli R. Viscido A. Latella G. Current management of severe ulcerative colitis. Nat. Clin. Pract. Gastroenterol. Hepatol. 2007 4 2 92 101 10.1038/ncpgasthep0687 17268544
    [Google Scholar]
  30. Alseekh S. Aharoni A. Brotman Y. Contrepois K. D’Auria J. Ewald J. Ewald C. J.; Fraser, P.D.; Giavalisco, P.; Hall, R.D.; Heinemann, M.; Link, H.; Luo, J.; Neumann, S.; Nielsen, J.; Perez de Souza, L.; Saito, K.; Sauer, U.; Schroeder, F.C.; Schuster, S.; Siuzdak, G.; Skirycz, A.; Sumner, L.W.; Snyder, M.P.; Tang, H.; Tohge, T.; Wang, Y.; Wen, W.; Wu, S.; Xu, G.; Zamboni, N.; Fernie, A.R. Mass spectrometry-based metabolomics: A guide for annotation, quantification and best reporting practices. Nat. Methods 2021 18 7 747 756 10.1038/s41592‑021‑01197‑1 34239102
    [Google Scholar]
  31. Yu S. Zou Y. Ma X. Wang D. Luo W. Tang Y. Mu D. Zhang R. Cheng X. Qiu L. Evolution of LC–MS/MS in clinical laboratories. Clin. Chim. Acta 2024 555 117797 10.1016/j.cca.2024.117797 38280490
    [Google Scholar]
  32. Causon T.J. Hann S. Review of sample preparation strategies for MS-based metabolomic studies in industrial biotechnology. Anal. Chim. Acta 2016 938 18 32 10.1016/j.aca.2016.07.033 27619083
    [Google Scholar]
  33. Šarenac T.M. Mikov M. Bile acid synthesis: From nature to the chemical modification and synthesis and their applications as drugs and nutrients. Front. Pharmacol. 2018 9 939 10.3389/fphar.2018.00939 30319399
    [Google Scholar]
  34. Kriaa A. Mariaule V. Jablaoui A. Rhimi S. Mkaouar H. Hernandez J. Korkmaz B. Lesner A. Maguin E. Aghdassi A. Rhimi M. Bile acids: Key players in inflammatory bowel diseases? Cells 2022 11 5 901 10.3390/cells11050901 35269523
    [Google Scholar]
  35. Peterson L.W. Artis D. Intestinal epithelial cells: Regulators of barrier function and immune homeostasis. Nat. Rev. Immunol. 2014 14 3 141 153 10.1038/nri3608 24566914
    [Google Scholar]
  36. Luo Z. Zhou W. Xie T. Xu W. Shi C. Xiao Z. Si Y. Ma Y. Ren Q. Di L. Shan J. The role of botanical triterpenoids and steroids in bile acid metabolism, transport, and signaling: Pharmacological and toxicological implications. Acta Pharm. Sin. B 2024 14 8 3385 3415 10.1016/j.apsb.2024.04.027 39220868
    [Google Scholar]
  37. Zeng H. Umar S. Rust B. Lazarova D. Bordonaro M. Secondary bile acids and short chain fatty acids in the colon: A focus on colonic microbiome, cell proliferation, inflammation, and cancer. Int. J. Mol. Sci. 2019 20 5 1214 10.3390/ijms20051214 30862015
    [Google Scholar]
  38. Luo H. Li M. Wang F. Yang Y. Wang Q. Zhao Y. Du F. Chen Y. Shen J. Zhao Q. Zeng J. Wang S. Chen M. Li X. Li W. Sun Y. Gu L. Wen Q. Xiao Z. Wu X. The role of intestinal stem cell within gut homeostasis: Focusing on its interplay with gut microbiota and the regulating pathways. Int. J. Biol. Sci. 2022 18 13 5185 5206 10.7150/ijbs.72600 35982910
    [Google Scholar]
  39. Wu H. Mu C. Xu L. Yu K. Shen L. Zhu W. Host-microbiota interaction in intestinal stem cell homeostasis. Gut Microbes 2024 16 1 2353399 10.1080/19490976.2024.2353399 38757687
    [Google Scholar]
  40. Chen S. Qin Z. Zhou S. Xu Y. Zhu Y. The emerging role of intestinal stem cells in ulcerative colitis. Front. Med. (Lausanne) 2025 12 1569328 10.3389/fmed.2025.1569328 40201327
    [Google Scholar]
  41. Staley C. Weingarden A.R. Khoruts A. Sadowsky M.J. Interaction of gut microbiota with bile acid metabolism and its influence on disease states. Appl. Microbiol. Biotechnol. 2017 101 1 47 64 10.1007/s00253‑016‑8006‑6 27888332
    [Google Scholar]
  42. Obata Y. Castaño Á. Boeing S. Bon-Frauches A.C. Fung C. Fallesen T. de Agüero M.G. Yilmaz B. Lopes R. Huseynova A. Horswell S. Maradana M.R. Boesmans W. Vanden Berghe P. Murray A.J. Stockinger B. Macpherson A.J. Pachnis V. Neuronal programming by microbiota regulates intestinal physiology. Nature 2020 578 7794 284 289 10.1038/s41586‑020‑1975‑8 32025031
    [Google Scholar]
  43. Guo X.Y. Liu X.J. Hao J.Y. Gut microbiota in ulcerative colitis: Insights on pathogenesis and treatment. J. Dig. Dis. 2020 21 3 147 159 10.1111/1751‑2980.12849 32040250
    [Google Scholar]
  44. Prosberg M. Bendtsen F. Vind I. Petersen A.M. Gluud L.L. The association between the gut microbiota and the inflammatory bowel disease activity: A systematic review and meta-analysis. Scand. J. Gastroenterol. 2016 51 12 1407 1415 10.1080/00365521.2016.1216587 27687331
    [Google Scholar]
  45. Komodromou I. Andreou E. Vlahoyiannis A. Christofidou M. Felekkis K. Pieri M. Giannaki C.D. Exploring the dynamic relationship between the gut microbiome and body composition across the human lifespan: A systematic review. Nutrients 2024 16 5 660 10.3390/nu16050660 38474787
    [Google Scholar]
  46. Tsai Y.C. Tai W.C. Liang C.M. Wu C.K. Tsai M.C. Hu W.H. Huang P.Y. Chen C.H. Kuo Y.H. Yao C.C. Chuah S.K. Alternations of the gut microbiota and the Firmicutes/Bacteroidetes ratio after biologic treatment in inflammatory bowel disease. J. Microbiol. Immunol. Infect. 2025 58 1 62 69 10.1016/j.jmii.2024.09.006 39393964
    [Google Scholar]
  47. Natividad J.M. Pinto-Sanchez M.I. Galipeau H.J. Jury J. Jordana M. Reinisch W. Collins S.M. Bercik P. Surette M.G. Allen-Vercoe E. Verdu E.F. Ecobiotherapy rich in Firmicutes decreases susceptibility to colitis in a humanized gnotobiotic mouse model. Inflamm. Bowel Dis. 2015 21 8 1883 1893 10.1097/MIB.0000000000000422 26060932
    [Google Scholar]
  48. Nomura K. Ishikawa D. Okahara K. Ito S. Haga K. Takahashi M. Arakawa A. Shibuya T. Osada T. Kuwahara-Arai K. Kirikae T. Nagahara A. Bacteroidetes species are correlated with disease activity in ulcerative colitis. J. Clin. Med. 2021 10 8 1749 1749 10.3390/jcm10081749 33920646
    [Google Scholar]
  49. Bousbaine D. Fisch L.I. London M. Bhagchandani P. Rezende de Castro T.B. Mimee M. Olesen S. Reis B.S. VanInsberghe D. Bortolatto J. Poyet M. Cheloha R.W. Sidney J. Ling J. Gupta A. Lu T.K. Sette A. Alm E.J. Moon J.J. Victora G.D. Mucida D. Ploegh H.L. Bilate A.M. A conserved Bacteroidetes antigen induces anti-inflammatory intestinal T lymphocytes. Science 2022 377 6606 660 666 10.1126/science.abg5645 35926021
    [Google Scholar]
  50. Wang C. Zhao J. Zhang H. Lee Y.K. Zhai Q. Chen W. Roles of intestinal bacteroides in human health and diseases. Crit. Rev. Food Sci. Nutr. 2021 61 21 3518 3536 10.1080/10408398.2020.1802695 32757948
    [Google Scholar]
  51. Litvak Y. Byndloss M.X. Tsolis R.M. Bäumler A.J. Dysbiotic proteobacteria expansion: A microbial signature of epithelial dysfunction. Curr. Opin. Microbiol. 2017 39 1 6 10.1016/j.mib.2017.07.003 28783509
    [Google Scholar]
  52. Vester-Andersen M.K. Mirsepasi-Lauridsen H.C. Prosberg M.V. Mortensen C.O. Träger C. Skovsen K. Thorkilgaard T. Nøjgaard C. Vind I. Krogfelt K.A. Sørensen N. Bendtsen F. Petersen A.M. Increased abundance of proteobacteria in aggressive Crohn’s disease seven years after diagnosis. Sci. Rep. 2019 9 1 13473 10.1038/s41598‑019‑49833‑3 31530835
    [Google Scholar]
  53. Mukhopadhya I. Hansen R. El-Omar E.M. Hold G.L. IBD—what role do Proteobacteria play? Nat. Rev. Gastroenterol. Hepatol. 2012 9 4 219 230 10.1038/nrgastro.2012.14 22349170
    [Google Scholar]
  54. Cai S. Yang Y. Kong Y. Guo Q. Xu Y. Xing P. Sun Y. Qian J. Xu R. Xie L. Hu Y. Wang M. Li M. Tian Y. Mao W. Gut bacteria erysipelatoclostridium and its related metabolite ptilosteroid a could predict radiation-induced intestinal injury. Front. Public Health 2022 10 862598 10.3389/fpubh.2022.862598 35419331
    [Google Scholar]
  55. Sheikh I.A. Bianchi-Smak J. Laubitz D. Schiro G. Midura-Kiela M.T. Besselsen D.G. Vedantam G. Jarmakiewicz S. Filip R. Ghishan F.K. Gao N. Kiela P.R. Transplant of microbiota from Crohn’s disease patients to germ-free mice results in colitis. Gut Microbes 2024 16 1 2333483 10.1080/19490976.2024.2333483 38532703
    [Google Scholar]
  56. Dicksved J. Schreiber O. Willing B. Petersson J. Rang S. Phillipson M. Holm L. Roos S. Lactobacillus reuteri maintains a functional mucosal barrier during DSS treatment despite mucus layer dysfunction. PLoS One 2012 7 9 e46399 10.1371/journal.pone.0046399 23029509
    [Google Scholar]
  57. Chen P. Zhong Y. Yu L. Hu J. Xie M. Inhibitory effect and mechanism of Lactobacillus reuteri on inflammation and apoptosis of intestinal epithelial cells. Shipin Kexue 2024 45 6 113 119 [in Chinese 10.7506/spkx1002‑6630‑20230427‑261
    [Google Scholar]
  58. Chen L. Zou Y. Peng J. Lu F. Yin Y. Li F. Yang J. Lactobacillus acidophilus suppresses colitis-associated activation of the IL-23/Th17 axis. J. Immunol. Res. 2015 2015 1 10 10.1155/2015/909514 25973440
    [Google Scholar]
  59. Parasar B. Chang P.V. BSH-TRAP: Bile salt hydrolase tagging and retrieval with activity-based probes. Methods Enzymol. 2022 664 85 102 10.1016/bs.mie.2021.12.002 35331380
    [Google Scholar]
  60. Labbé A. Ganopolsky J.G. Martoni C.J. Prakash S. Jones M.L. Bacterial bile metabolising gene abundance in Crohn’s, ulcerative colitis and type 2 diabetes metagenomes. PLoS One 2014 9 12 e115175 10.1371/journal.pone.0115175 25517115
    [Google Scholar]
  61. Crudele L. Gadaleta R.M. Cariello M. Moschetta A. Gut microbiota in the pathogenesis and therapeutic approaches of diabetes. EBioMedicine 2023 97 104821 10.1016/j.ebiom.2023.104821 37804567
    [Google Scholar]
  62. Foley M.H. O’Flaherty S. Allen G. Rivera A.J. Stewart A.K. Barrangou R. Theriot C.M. Lactobacillus bile salt hydrolase substrate specificity governs bacterial fitness and host colonization. Proc. Natl. Acad. Sci. USA 2021 118 6 e2017709118 10.1073/pnas.2017709118 33526676
    [Google Scholar]
  63. Wong W.Y. Chan B.D. Sham T.T. Lee M.M.L. Chan C.O. Chau C.T. Mok D.K.W. Kwan Y.W. Tai W.C.S. Lactobacillus casei Strain Shirota ameliorates dextran sulfate sodium-induced colitis in mice by increasing taurine-conjugated bile acids and inhibiting NF-κB signaling via stabilization of IκBα. Front. Nutr. 2022 9 816836 10.3389/fnut.2022.816836 35529468
    [Google Scholar]
  64. Mu Q. Tavella V.J. Luo X.M. Role of Lactobacillus reuteri in human health and diseases. Front. Microbiol. 2018 9 757 10.3389/fmicb.2018.00757 29725324
    [Google Scholar]
  65. Xing J.H. Niu T.M. Zou B.S. Yang G.L. Shi C.W. Yan Q.S. Sun M.J. Yu T. Zhang S.M. Feng X.Z. Fan S.H. Huang H.B. Wang J.H. Li M.H. Jiang Y.L. Wang J.Z. Cao X. Wang N. Zeng Y. Hu J.T. Zhang D. Sun W.S. Yang W.T. Wang C.F. Gut microbiota-derived LCA mediates the protective effect of PEDV infection in piglets. Microbiome 2024 12 1 20 10.1186/s40168‑023‑01734‑4 38317217
    [Google Scholar]
  66. Latella G. Viscido A. Controversial contribution of Th17/IL-17 toward the immune response in intestinal fibrosis. Dig. Dis. Sci. 2020 65 5 1299 1306 10.1007/s10620‑020‑06161‑1 32124197
    [Google Scholar]
  67. Zhao J. Lu Q. Liu Y. Shi Z. Hu L. Zeng Z. Tu Y. Xiao Z. Xu Q. Th17 cells in inflammatory bowel disease: Cytokines, plasticity, and therapies. J. Immunol. Res. 2021 2021 1 14 10.1155/2021/8816041 33553436
    [Google Scholar]
  68. Zong Y. Deng K. Chong W.P. Regulation of Treg cells by cytokine signaling and co-stimulatory molecules. Front. Immunol. 2024 15 1387975 10.3389/fimmu.2024.1387975 38807592
    [Google Scholar]
  69. Zhang S. Zhong R. Tang S. Chen L. Zhang H. Metabolic regulation of the Th17/Treg balance in inflammatory bowel disease. Pharmacol. Res. 2024 203 107184 10.1016/j.phrs.2024.107184 38615874
    [Google Scholar]
  70. Kałużna A. Olczyk P. Komosińska-Vassev K. The role of innate and adaptive immune cells in the pathogenesis and development of the inflammatory response in ulcerative colitis. J. Clin. Med. 2022 11 2 400 400 10.3390/jcm11020400 35054093
    [Google Scholar]
  71. Magrone T. Jirillo E. The interplay between the gut immune system and microbiota in health and disease: nutraceutical intervention for restoring intestinal homeostasis. Curr. Pharm. Des. 2012 19 7 1329 1342 10.2174/138161213804805793 23151182
    [Google Scholar]
  72. Chang Y. Zhai L. Peng J. Wu H. Bian Z. Xiao H. Phytochemicals as regulators of Th17/Treg balance in inflammatory bowel diseases. Biomed. Pharmacother. 2021 141 111931 10.1016/j.biopha.2021.111931 34328111
    [Google Scholar]
  73. Hang S. Paik D. Yao L. Kim E. Trinath J. Lu J. Ha S. Nelson B.N. Kelly S.P. Wu L. Zheng Y. Longman R.S. Rastinejad F. Devlin A.S. Krout M.R. Fischbach M.A. Littman D.R. Huh J.R. Bile acid metabolites control TH17 and Treg cell differentiation. Nature 2019 576 7785 143 148 10.1038/s41586‑019‑1785‑z 31776512
    [Google Scholar]
  74. Fiorillo B. Roselli R. Finamore C. Biagioli M. di Giorgio C. Bordoni M. Conflitti P. Marchianò S. Bellini R. Rapacciuolo P. Cassiano C. Limongelli V. Sepe V. Catalanotti B. Fiorucci S. Zampella A. Discovery of a novel class of dual GPBAR1 agonists-RORγt inverse agonists for the treatment of IL-17-mediated disorders. ACS Omega 2023 8 6 5983 5994 10.1021/acsomega.2c07907 36816679
    [Google Scholar]
  75. Zhang Y. Gao X. Gao S. Liu Y. Wang W. Feng Y. Pei L. Sun Z. Liu L. Wang C. Effect of gut flora mediated‐bile acid metabolism on intestinal immune microenvironment. Immunology 2023 170 3 301 318 10.1111/imm.13672 37317655
    [Google Scholar]
  76. Shultz L.D. Brehm M.A. Garcia-Martinez J.V. Greiner D.L. Humanized mice for immune system investigation: Progress, promise and challenges. Nat. Rev. Immunol. 2012 12 11 786 798 10.1038/nri3311 23059428
    [Google Scholar]
  77. Mestas J. Hughes C.C.W. Of mice and not men: Differences between mouse and human immunology. J. Immunol. 2004 172 5 2731 2738 10.4049/jimmunol.172.5.2731 14978070
    [Google Scholar]
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