Skip to content
2000
Volume 22, Issue 7
  • ISSN: 1567-2018
  • E-ISSN: 1875-5704

Abstract

Background

Our previous studies have found that Wumei Pills can regulate the intestinal flora to inhibit chemotherapy-induced intestinal mucositis (CIM). However, there is still insufficient evidence to confirm that intestinal flora is the main link in the regulation of CIM by Wumei Pills, and its downstream mechanism is still unclear.

Methods

We first obtained the signal pathway of the intervention of Wumei Pill on CIM through network pharmacological analysis and then transplanted the bacterial solution into CIM mice, combined with Western Blot, HE, ELISA and other biological technology-related proteins and inflammatory factors.

Results

It showed that 97 kinds of effective ingredients and 205 kinds of targets of Wumei pills were screened out and the potential mechanism of Wumei Pills on CIM may be the NF-κB signaling pathway. In contrast with the control group, the results displayed that the weight, food intake, and mice’s colon length were apparently decreased in the 5-Fu group, while the diarrhea score was increased. However, FMT reversed this change, and the difference was statistically significant. Additionally, FMT could improve the pathological state of inflammatory cell infiltration in mice, reduce histopathological scores of colon and jejunum, decrease the expression levels of IL-1β, MPO, TNF-α, and IL-6, reverse the activation of signaling pathway named TLR4/Myd88/NF-κB and down-regulate protein expression, thereby exerting its anti-inflammatory activities. Further experiments have found that FMT could reverse the decreasing of tight junction proteins and mucins caused by 5-Fu, thereby repairing the intestinal mucosal barrier, and FMT could also increase the content of acetic acid, propanoic acid, and butanoic acid in the feces of 5-Fu group.

Conclusion

FMT can defend the intestinal mucosal barrier integrality by increasing the content of exercise fatty acids, and its mechanism may be in connection with its inhibition of TLR4/MyD88/NF-κB signal pathway to relieve inflammation.

Loading

Article metrics loading...

/content/journals/cdd/10.2174/0115672018304338241003095955
2024-10-11
2025-09-18
Loading full text...

Full text loading...

References

  1. DahlgrenD. SjöblomM. HellströmP.M. LennernäsH. Chemotherapeutics-induced intestinal mucositis: Pathophysiology and potential treatment strategies.Front. Pharmacol.20211268141710.3389/fphar.2021.68141734017262
    [Google Scholar]
  2. BullardB.M. McDonaldS.J. CardaciT.D. VanderVeenB.N. MurphyE.A. Nonpharmacological approaches for improving gut resilience to chemotherapy.Curr. Opin. Support. Palliat. Care202216315116010.1097/SPC.000000000000059935862879
    [Google Scholar]
  3. HechtJ.R. Gastrointestinal toxicity or irinotecan.Oncology (Williston Park)199812872789726096
    [Google Scholar]
  4. ZhangJ. TangH. LiuZ. ChenB. Effects of major parameters of nanoparticles on their physical and chemical properties and recent application of nanodrug delivery system in targeted chemotherapy.Int. J. Nanomedicine2017128483849310.2147/IJN.S14835929238188
    [Google Scholar]
  5. RosenthalD.I. MendozaT.R. FullerC.D. HutchesonK.A. WangX.S. HannaE.Y. LuC. GardenA.S. MorrisonW.H. CleelandC.S. GunnG.B. Patterns of symptom burden during radiotherapy or concurrent chemoradiotherapy for head and neck cancer: A prospective analysis using the University of Texas MD Anderson Cancer Center Symptom Inventory-Head and Neck Module.Cancer2014120131975198410.1002/cncr.2867224711162
    [Google Scholar]
  6. VindigniS.M. SurawiczC.M. Fecal microbiota transplantation.Gastroenterol. Clin. North Am.201746117118510.1016/j.gtc.2016.09.01228164849
    [Google Scholar]
  7. MinkoffN.Z. AslamS. MedinaM. Tanner-SmithE.E. ZackularJ.P. AcraS. NicholsonM.R. ImdadA. Fecal microbiota transplantation for the treatment of recurrent Clostridioides difficile (Clostridium difficile).Cochrane Database Syst. Rev.202344CD01387137096495
    [Google Scholar]
  8. DoosettyS. UmehC. EastwoodW. SamreenI. PenchalaA. KaurH. ChilingaC. KaurG. MohtaT. NakkaS. TangiralaP. NakkaS. Efficacy of fecal microbiota (REBYOTA) in recurrent clostridium difficile infections: A systematic review and meta-analysis.Cureus2024164e5886210.7759/cureus.5886238800285
    [Google Scholar]
  9. WangY. HuntA. DanzigerL. DrwiegaE.N. A comparison of currently available and investigational fecal microbiota transplant products for recurrent Clostridioides difficile infection.Antibiotics (Basel)202413543610.3390/antibiotics1305043638786164
    [Google Scholar]
  10. StoffR. WolfY. BoursiB. Fecal Microbiota Transplantation as a Cancer Therapeutic.Cancer J.202329210210810.1097/PPO.000000000000065136957981
    [Google Scholar]
  11. BaruchE.N. YoungsterI. Ben-BetzalelG. OrtenbergR. LahatA. KatzL. AdlerK. Dick-NeculaD. RaskinS. BlochN. RotinD. AnafiL. AviviC. MelnichenkoJ. Steinberg-SilmanY. MamtaniR. HaratiH. AsherN. Shapira-FrommerR. Brosh-NissimovT. EshetY. Ben-SimonS. ZivO. KhanM.A.W. AmitM. AjamiN.J. BarshackI. SchachterJ. WargoJ.A. KorenO. MarkelG. BoursiB. Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients.Science2021371652960260910.1126/science.abb592033303685
    [Google Scholar]
  12. ChangC.W. LeeH.C. LiL.H. Chiang ChiauJ.S. WangT.E. ChuangW.H. ChenM.J. WangH.Y. ShihS.C. LiuC.Y. TsaiT.H. ChenY.J. Fecal microbiota transplantation prevents intestinal injury, upregulation of toll-like receptors, and 5-fluorouracil/oxaliplatin-induced toxicity in colorectal cancer.Int. J. Mol. Sci.202021238610.3390/ijms2102038631936237
    [Google Scholar]
  13. ZhengX. MaiL. XuY. WuM. ChenL. ChenB. SuZ. ChenJ. ChenH. LaiZ. XieY. Brucea javanica oil alleviates intestinal mucosal injury induced by chemotherapeutic agent 5-fluorouracil in mice.Front. Pharmacol.202314113607610.3389/fphar.2023.113607636895947
    [Google Scholar]
  14. VitalK.D. PiresL.O. GallottiB. SilvaJ.L. Lima de JesusL.C. Alvarez-LeiteJ.I. FerreiraÊ. de Carvalho AzevedoV.A. Santos MartinsF. Nascimento CardosoV. Antunes FernandesS.O. Atorvastatin attenuates intestinal mucositis induced by 5-fluorouracil in mice by modulating the epithelial barrier and inflammatory response.J. Chemother.2024611810.1080/1120009X.2024.234502738711347
    [Google Scholar]
  15. LuD.X. LiuF. WuH. LiuH.X. ChenB.Y. YanJ. LuY. SunZ.G. Wumei pills attenuates 5-fluorouracil-induced intestinal mucositis through Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway and microbiota regulation.World J. Gastroenterol.202228324574459910.3748/wjg.v28.i32.457436157934
    [Google Scholar]
  16. Jin-chengL.I. Zhen-changL.I.U. Dong-meiL.I. Efficacy observation of Wumei pill and montmorillonite powder on chemotherapy-induced diarrhea.Shanxi J. Tradit. Chin. Med.202440081921
    [Google Scholar]
  17. DongxueL.U. JingY.A.N. ZhiguangS.U.N. Clinical effecacy and mechanism of wumei pills in the treatment of chemotherapy-induced intestinal mucositis.J. Nanjing Univ. Tradit. Chin. Med.20213703371375
    [Google Scholar]
  18. WangZ. ZhouY. LuoA. HengX. LiuJ. WangH. ChuW. Lactobacillus salivarius CPU-01 ameliorates temozolomide-induced intestinal mucositis by modulating gut microbiota, maintaining intestinal barrier, and blocking pro-inflammatory cytokines.Probiotics Antimicrob. Proteins20231551079109110.1007/s12602‑022‑09955‑z35639268
    [Google Scholar]
  19. HeY. LiF. ZhangY. ZhuX. LinZ. LiL. NawazS. KulyarM.F.A. IqbalM. LiJ. Pediococcus pentosaceus PP34 ameliorates 5-fluorouracil-induced intestinal mucositis via inhibiting oxidative stress and restoring the gut microbiota.Probiotics Antimicrob. Proteins202410.1007/s12602‑024‑10324‑139046671
    [Google Scholar]
  20. RuJ. LiP. WangJ. ZhouW. LiB. HuangC. LiP. GuoZ. TaoW. YangY. XuX. LiY. WangY. YangL. TCMSP: A database of systems pharmacology for drug discovery from herbal medicines.J. Cheminform.2014611310.1186/1758‑2946‑6‑1324735618
    [Google Scholar]
  21. DuanZ. WangY. LuZ. TianL. XiaZ.Q. WangK. ChenT. WangR. FengZ. ShiG. XuX. BuF. DingY. JiangF. ZhouJ. WangQ. ChenY. Wumei Wan attenuates angiogenesis and inflammation by modulating RAGE signaling pathway in IBD: Network pharmacology analysis and experimental evidence.Phytomedicine202311115465810.1016/j.phymed.2023.15465836706698
    [Google Scholar]
  22. LiuZ. GuoF. WangY. LiC. ZhangX. LiH. DiaoL. GuJ. WangW. LiD. HeF. BATMAN-TCM: A bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine.Sci. Rep.2016612114610.1038/srep2114626879404
    [Google Scholar]
  23. LinF. ZhangG. YangX. WangM. WangR. WanM. WangJ. WuB. YanT. JiaY. A network pharmacology approach and experimental validation to investigate the anticancer mechanism and potential active targets of ethanol extract of Wei-Tong-Xin against colorectal cancer through induction of apoptosis via PI3K/AKT signaling pathway.J. Ethnopharmacol.202330311593310.1016/j.jep.2022.11593336403742
    [Google Scholar]
  24. BreuzaL. PouxS. EstreicherA. FamigliettiM.L. MagraneM. TognolliM. BridgeA. BaratinD. RedaschiN. The UniProtKB guide to the human proteome.Database (Oxford)20162016bav12010.1093/database/bav12026896845
    [Google Scholar]
  25. StelzerG. RosenN. PlaschkesI. ZimmermanS. TwikM. FishilevichS. SteinT.I. NudelR. LiederI. MazorY. The GeneCards suite: From gene data mining to disease genome sequence analyses.Curr. Protoc. Bioinformatics2016541.30.11.30.3310.1002/cpbi.5
    [Google Scholar]
  26. AmbergerJ.S. HamoshA. Searching Online Mendelian Inheritance in Man (OMIM): A knowledgebase of human genes and genetic phenotypes.Curr. Protoc. Bioinformatics20175812.1, 1210.1002/cpbi.2728654725
    [Google Scholar]
  27. SzklarczykD. KirschR. KoutrouliM. NastouK. MehryaryF. HachilifR. GableA.L. FangT. DonchevaN.T. PyysaloS. BorkP. JensenL.J. von MeringC. The STRING database in 2023: Protein–protein association networks and functional enrichment analyses for any sequenced genome of interest.Nucleic Acids Res.202351D1D638D64610.1093/nar/gkac100036370105
    [Google Scholar]
  28. BaQ. LiJ. HuangC. LiJ. ChuR. WuY. WangH. Topological, functional, and dynamic properties of the protein interaction networks rewired by benzo(a)pyrene.Toxicol. Appl. Pharmacol.20152832839110.1016/j.taap.2015.01.00625596431
    [Google Scholar]
  29. GuoR. ZhangX. SuJ. XuH. ZhangY. ZhangF. LiD. ZhangY. XiaoX. MaS. YangH. Identifying potential quality markers of Xin-Su-Ning capsules acting on arrhythmia by integrating UHPLC-LTQ-Orbitrap, ADME prediction and network target analysis.Phytomedicine20184411712810.1016/j.phymed.2018.01.01929526583
    [Google Scholar]
  30. XieR. LiB. JiaL. LiY. Identification of core genes and pathways in melanoma metastasis via bioinformatics analysis.Int. J. Mol. Sci.202223279410.3390/ijms2302079435054979
    [Google Scholar]
  31. ZhouD. WangM. ZhangY. WangK. ZhaoM. WangY. WangX. YuR. ZhouX. Screening and identification of LMNB1 and DLGAP5, two key biomarkers in gliomas.Biosci. Rep.2021415BSR2021023110.1042/BSR2021023133956061
    [Google Scholar]
  32. XiaoJ. ZhangY. AURKB as a Promising Prognostic Biomarker in Hepatocellular Carcinoma.Evol. Bioinform. Online20211710.1177/1176934321105758934866894
    [Google Scholar]
  33. MissiuroP.V. LiuK. ZouL. RossB.C. ZhaoG. LiuJ.S. GeH. Information flow analysis of interactome networks.PLOS Comput. Biol.200954e100035010.1371/journal.pcbi.100035019503817
    [Google Scholar]
  34. RamanK. DamarajuN. JoshiG.K. The organisational structure of protein networks: Revisiting the centrality–lethality hypothesis.Syst. Synth. Biol.201481738110.1007/s11693‑013‑9123‑524592293
    [Google Scholar]
  35. TangY. LiM. WangJ. PanY. WuF.X. CytoNCA: A cytoscape plugin for centrality analysis and evaluation of protein interaction networks.Biosystems2015127677210.1016/j.biosystems.2014.11.00525451770
    [Google Scholar]
  36. ZhaoY. TaoS. WangQ. LiuY. YangW. ZhangS. SuZ. MaX. A network-based pharmacological study on the mechanism of action of muscone in breast cancer.Transl. Cancer Res.20221151195120610.21037/tcr‑22‑66735706803
    [Google Scholar]
  37. KanehisaM. FurumichiM. SatoY. KawashimaM. Ishiguro-WatanabeM. KEGG for taxonomy-based analysis of pathways and genomes.Nucleic Acids Res.202351D1D587D59210.1093/nar/gkac96336300620
    [Google Scholar]
  38. HuangJ. HwangA.Y.M. JiaY. KimB. IskandarM. MohammedA.I. CirilloN. Experimental chemotherapy-induced mucositis: A scoping review guiding the design of suitable preclinical models.Int. J. Mol. Sci.202223231543410.3390/ijms23231543436499758
    [Google Scholar]
  39. LiH.L. LuL. WangX.S. QinL.Y. WangP. QiuS.P. WuH. HuangF. ZhangB.B. ShiH.L. WuX.J. Alteration of gut microbiota and inflammatory cytokine/chemokine profiles in 5-fluorouracil induced intestinal mucositis.Front. Cell. Infect. Microbiol.2017745510.3389/fcimb.2017.0045529124041
    [Google Scholar]
  40. KullenbergF. PetersK. SjöblomM. HeindryckxF. DahlgrenD. LennernäsH. Anakinra and dexamethasone treatment of idarubicin-induced mucositis and diarrhoea in rats.Basic Clin. Pharmacol. Toxicol.2023132650751610.1111/bcpt.1385136878867
    [Google Scholar]
  41. WeiL. WenX.S. XianC.J. Chemotherapy-induced intestinal microbiota dysbiosis impairs mucosal homeostasis by modulating toll-like receptor signaling pathways.Int. J. Mol. Sci.20212217947410.3390/ijms2217947434502383
    [Google Scholar]
  42. KawasakiY. KakimotoK. TanakaY. ShimizuH. NishidaK. NumaK. KinoshitaN. TatsumiY. NakazawaK. KoshibaR. HirataY. OtaK. SakiyamaN. TerazawaT. TakeuchiT. MiyazakiT. GotoM. YokotaH. MakizakiY. TanakaY. NakajimaS. OhnoH. HiguchiK. NakamuraS. NishikawaH. Relationship between chemotherapy-induced diarrhea and intestinal microbiome composition.Digestion2023104535736910.1159/00052828237231829
    [Google Scholar]
  43. YeungC.Y. Chiang ChiauJ.S. ChengM.L. ChanW.T. ChangS.W. ChangY.H. JiangC.B. LeeH.C. Modulations of probiotics on gut microbiota in a 5-fluorouracil-induced mouse model of mucositis.J. Gastroenterol. Hepatol.202035580681410.1111/jgh.1489031674687
    [Google Scholar]
  44. WangL. WangR. WeiG. WangS. DuG. Dihydrotanshinone attenuates chemotherapy-induced intestinal mucositis and alters fecal microbiota in mice.Biomed. Pharmacother.202012811026210.1016/j.biopha.2020.11026232447214
    [Google Scholar]
  45. ChenH. ZhangF. LiR. LiuY. WangX. ZhangX. XuC. LiY. GuoY. YaoQ. Berberine regulates fecal metabolites to ameliorate 5-fluorouracil induced intestinal mucositis through modulating gut microbiota.Biomed. Pharmacother.202012410982910.1016/j.biopha.2020.10982931958765
    [Google Scholar]
  46. da Silva FerreiraA.R. WardillH.R. TissingW.J.E. HarmsenH.J.M. Pitfalls and novel experimental approaches to optimize microbial interventions for chemotherapy-induced gastrointestinal mucositis.Curr. Opin. Support. Palliat. Care202014212713410.1097/SPC.000000000000049732324645
    [Google Scholar]
  47. VitkovL. SinghJ. SchauerC. MinnichB. KrunićJ. OberthalerH. GamsjaegerS. HerrmannM. KnopfJ. HannigM. Breaking the gingival barrier in periodontitis.Int. J. Mol. Sci.2023245454410.3390/ijms2405454436901974
    [Google Scholar]
  48. SchoultzI. KeitaÅ.V. Cellular and molecular therapeutic targets in inflammatory bowel disease-focusing on intestinal barrier function.Cells20198219310.3390/cells802019330813280
    [Google Scholar]
  49. EstévezJ. MartínezV. The local activation of Toll-like Receptor 7 (TLR7) modulates colonic epithelial barrier function in rats.Int. J. Mol. Sci.2023242125410.3390/ijms2402125436674770
    [Google Scholar]
  50. CarioE. GerkenG. PodolskyD.K. Toll-like receptor 2 controls mucosal inflammation by regulating epithelial barrier function.Gastroenterology200713241359137410.1053/j.gastro.2007.02.05617408640
    [Google Scholar]
  51. KawaiT. AkiraS. TLR signaling.Semin. Immunol.2007191243210.1016/j.smim.2006.12.00417275323
    [Google Scholar]
  52. TanY. ZanoniI. CullenT.W. GoodmanA.L. KaganJ.C. Mechanisms of Toll-like receptor 4 endocytosis reveal acommonimune evasions straegy used by pathogenic and commensal bacteria.Immunity201543590992210.1016/j.immuni.2015.10.00826546281
    [Google Scholar]
  53. IzadparastF. Riahi-ZajaniB. YarmohammadiF. HayesA.W. KarimiG. Protective effect of berberine against LPS-induced injury in the intestine: A review.Cell Cycle202221222365237810.1080/15384101.2022.210068235852392
    [Google Scholar]
  54. ZhangT. LuS.H. BiQ. LiangL. WangY.F. YangX.X. GuW. YuJ. Volatile oil from amomi fructus attenuates 5-flfluorouracil -induced intestinal mucositisd.Front. Pharmacol.2017878610.3389/fphar.2017.0078629170638
    [Google Scholar]
  55. ZhaiZ. BoqueteJ.P. LemaitreB. Cell-specific Imd-NF-κB responses enable simultaneous antibacterial immunity and intestinal epithelial cell shedding upon bacterial infection.Immunity2018485897910.e710.1016/j.immuni.2018.04.01029752064
    [Google Scholar]
  56. TurnerJ.R. Intestinal mucosal barrier function in health and disease.Nat. Rev. Immunol.200991179980910.1038/nri265319855405
    [Google Scholar]
  57. ArrietaM.C. MadsenK. DoyleJ. MeddingsJ. Reducing small intestinal permeability attenuates colitis in the IL10 gene-deficient mouse.Gut2009581414810.1136/gut.2008.15088818829978
    [Google Scholar]
  58. WengY.J. GanH.Y. LiX. HuangY. LiZ.C. DengH.M. ChenS.Z. ZhouY. WangL.S. HanY.P. TanY.F. SongY.J. DuZ.M. LiuY.Y. WangY. QinN. BaiY. YangR.F. BiY.J. ZhiF.C. Correlation of diet, microbiota and metabolite networks in inflammatory bowel disease.J. Dig. Dis.201920944745910.1111/1751‑2980.1279531240835
    [Google Scholar]
  59. MannE.R. LamY.K. UhligH.H. Short-chain fatty acids: Linking diet, the microbiome and immunity.Nat. Rev. Immunol.202424857759510.1038/s41577‑024‑01014‑838565643
    [Google Scholar]
/content/journals/cdd/10.2174/0115672018304338241003095955
Loading
/content/journals/cdd/10.2174/0115672018304338241003095955
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test