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2000
Volume 25, Issue 3
  • ISSN: 1871-5265
  • E-ISSN: 2212-3989

Abstract

Background

is an opportunistic infection that can lead to antibiotic-associated diarrhea and toxic megacolon.

Objective

This systematic review study aimed to investigate polyphenols' antibacterial and anti-toxin properties and their effects on reducing complications related to Infections (CDI).

Methods

This systematic review was conducted following the PRISMA guideline 2020. Multiple databases, including Web of Science, PubMed, Cochrane Library, EMBASE, and Scopus, were searched thoroughly for existing literature. After considering the inclusion and exclusion criteria for the review, 18 articles were included. Data were collected and registered into an Excel file for further investigations and conclusions.

Results

Polyphenols by reducing Reactive Oxygen Species (ROS) levels, increasing inflammatory factor Interleukin 10 (IL-10), reducing Nuclear Factor kappa B (NF-κB) and Tumour Necrosis Factor-α (TNF-α), IL-6, IL-1α, IL-1β, Granulocyte Colony-stimulating Factor (G-CSF), and Monocyte Chemoattractant Protein-1 (MCP-1) and Macrophage Inflammatory Protein-1 alpha (MIP-1α) levels, and regulating the expression of Bcl-2 and Bax, make the growth and replication conditions of more difficult and prevent it from producing toxins. Furthermore, polyphenols can exhibit prebiotic properties, promoting the growth of beneficial and species and consequently regulating gut microbiota, exerting antimicrobial activities against . They also induce their beneficial effects by inhibiting the production of TcdA and TcdB.

Conclusion

Polyphenols have been reported to inhibit growth and toxin production by several mechanisms in preclinical studies. However, more clinical studies are needed to investigate their safety in humans.

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References

  1. Turuvekere Vittala MurthyN. AgrahariV. ChauhanH. Polyphenols against infectious diseases: Controlled release nano-formulations.Eur. J. Pharm. Biopharm.2021161667910.1016/j.ejpb.2021.02.003 33588032
    [Google Scholar]
  2. MotamediH. FathollahiM. AbiriR. KadivarianS. RostamianM. AlvandiA. A worldwide systematic review and meta-analysis of bacteria related to antibiotic-associated diarrhea in hospitalized patients.PLoS One20211612e026066710.1371/journal.pone.0260667 34879104
    [Google Scholar]
  3. BeydounA.S. StabenauK.A. AltmanK.W. JohnstonN. Cancer Risk in Barrett’s Esophagus: A Clinical Review.Int. J. Mol. Sci.2023247601810.3390/ijms24076018 37046992
    [Google Scholar]
  4. MullishB.H. WilliamsH.R.T. Clostridium difficile infection and antibiotic-associated diarrhoea.Clin. Med. (Lond.)201818323724110.7861/clinmedicine.18‑3‑237 29858434
    [Google Scholar]
  5. Di BellaS. AscenziP. SiarakasS. PetrosilloN. Di MasiA. Clostridium difficile Toxins A and B: Insights into Pathogenic Properties and Extraintestinal Effects.Toxins20168513410.3390/toxins8050134 27153087
    [Google Scholar]
  6. FeuerstadtP. BoulesM. StongL. Clinical complications in patients with primary and recurrent Clostridioides difficile infection: A real-world data analysis.SAGE Open Med.2021910.1177/2050312120986733 33505698
    [Google Scholar]
  7. CzepielJ. DróżdżM. PituchH. Clostridium difficile infection review.Eur. J. Clin. Microbiol. Infect. Dis.20193871211122110.1007/s10096‑019‑03539‑6 30945014
    [Google Scholar]
  8. RafeyA. JahanS. FarooqU. Antibiotics Associated With Clostridium difficile Infection.Cureus2023155e39029 37323360
    [Google Scholar]
  9. MohsenS. DickinsonJ.A. SomayajiR. Update on the adverse effects of antimicrobial therapies in community practice.Can. Fam. Physician2020669651659 32933978
    [Google Scholar]
  10. DeyP. MoludiJ. Clostridium difficile infection and gut microbiota: From fundamentals to microbiota-centered strategies.Viral, Parasitic, Bacterial, and Fungal Infections.Academic Press202354756110.1016/B978‑0‑323‑85730‑7.00030‑8
    [Google Scholar]
  11. MansoT. LoresM. de MiguelT. Antimicrobial Activity of Polyphenols and Natural Polyphenolic Extracts on Clinical Isolates.Antibiotics (Basel)20211114610.3390/antibiotics11010046 35052923
    [Google Scholar]
  12. KhaledifarA. Khosravi FarsaniM.R. RaeisiE. Berberine efficacy against Doxorubicin-induced cardiotoxicity: A systematic review.Journal of Herbmed Pharmacology202312218719310.34172/jhp.2023.19
    [Google Scholar]
  13. ShaitoA. ThuanD.T.B. PhuH.T. Herbal Medicine for Cardiovascular Diseases: Efficacy, Mechanisms, and Safety.Front. Pharmacol.20201142210.3389/fphar.2020.00422 32317975
    [Google Scholar]
  14. RaeisiE. Shahbazi-GahroueiD. HeidarianE. Pineapple extract as an efficient anticancer agent in treating human cancer cells.Immunopharmacogenetics201916
    [Google Scholar]
  15. BertelliA. BiagiM. CorsiniM. BainiG. CappellucciG. MiraldiE. Polyphenols: From theory to practice.Foods20211011259510.3390/foods10112595 34828876
    [Google Scholar]
  16. de AraújoF.F. de Paulo FariasD. Neri-NumaI.A. PastoreG.M. Polyphenols and their applications: An approach in food chemistry and innovation potential.Food Chem.202133812753510.1016/j.foodchem.2020.127535 32798817
    [Google Scholar]
  17. Montenegro-LandívarM.F. Tapia-QuirósP. VecinoX. Polyphenols and their potential role to fight viral diseases: An overview.Sci. Total Environ.202180114971910.1016/j.scitotenv.2021.149719 34438146
    [Google Scholar]
  18. FinegoldS.M. SummanenP.H. CorbettK. DownesJ. HenningS.M. LiZ. Pomegranate extract exhibits in vitro activity against Clostridium difficile.Nutrition201430101210121210.1016/j.nut.2014.02.029 24976424
    [Google Scholar]
  19. DawsonL.F. StablerR.A. WrenB.W. Assessing the role of p-cresol tolerance in Clostridium difficile.J. Med. Microbiol.200857674574910.1099/jmm.0.47744‑0 18480332
    [Google Scholar]
  20. DawsonL.F. DonahueE.H. CartmanS.T. The analysis of para-cresol production and tolerance in Clostridium difficile 027 and 012 strains.BMC Microbiol.20111118610.1186/1471‑2180‑11‑86 21527013
    [Google Scholar]
  21. PatelR YangN Inhibiting hospital associated infection of toxigenic Clostridium difficile using natural spice-turmeric (Curcumin).Off j Am Coll Gastroenterol2010105S122
    [Google Scholar]
  22. SrinivasanN. SubramaniamD. VarmanA. RamanujamR.P. HouchenC.W. AnantS. T2065 curcumin suppresses intestinal epithelial response to Clostridium difficile Infection: Role of cell signaling pathways.Gastroenterology20091365A-63110.1016/S0016‑5085(09)62911‑5
    [Google Scholar]
  23. KeatesA.C. CastagliuoloI. QiuB. NikulassonS. SenguptaA. PothoulakisC. CGRP upregulation in dorsal root ganglia and ileal mucosa during Clostridium difficile toxin A-induced enteritis.Am. J. Physiol.19982741G196G202 9458790
    [Google Scholar]
  24. McVeyD.C. VignaS.R. The capsaicin VR1 receptor mediates substance P release in toxin A-induced enteritis in rats.Peptides20012291439144610.1016/S0196‑9781(01)00463‑6 11514026
    [Google Scholar]
  25. KamathS. SkariyachanS. Novel insight from computational virtual screening depict the binding potential of selected phytotherapeutics against probable drug targets of Clostridium difficile.Interdiscip. Sci.201810358360410.1007/s12539‑017‑0215‑x 28217823
    [Google Scholar]
  26. WuX. AlamM.Z. FengL. TsutsumiL.S. SunD. HurdleJ.G. Prospects for flavonoid and related phytochemicals as nature-inspired treatments for Clostridium difficile infection.J. Appl. Microbiol.20141161233110.1111/jam.12344 24479135
    [Google Scholar]
  27. LangA. SalomonN. WuJ.C.Y. Curcumin in combination with mesalamine induces remission in patients with mild-to-moderate ulcerative colitis in a randomized controlled trial.Clin. Gastroenterol. Hepatol.201513814441449.e110.1016/j.cgh.2015.02.019 25724700
    [Google Scholar]
  28. BlandS.D. VenableE.B. McPhersonJ.L. AtkinsonR.L. Effects of liposomal-curcumin on five opportunistic bacterial strains found in the equine hindgut - preliminary study.J. Anim. Sci. Technol.20175911510.1186/s40781‑017‑0138‑4 28638626
    [Google Scholar]
  29. VignaS.R. Intraluminal administration of resiniferatoxin protects against Clostridium difficile toxin a-induced colitis.Gastroenterol. Res. Pract.201720171810.1155/2017/8438172 28484490
    [Google Scholar]
  30. SukumarM.R. KönigB. Pomegranate extract specifically inhibits Clostridium difficile growth and toxin production without disturbing the beneficial bacteria in vitro.Infect. Drug Resist.2018112357236210.2147/IDR.S163484 30532567
    [Google Scholar]
  31. TanakaY. KimuraS. IshiiY. TatedaK. Equol inhibits growth and spore formation of Clostridioides difficile.J. Appl. Microbiol.2019127393294010.1111/jam.14353 31211883
    [Google Scholar]
  32. LakesJ.E. RichardsC.I. FlytheM.D. Inhibition of bacteroidetes and firmicutes by select phytochemicals.Anaerobe20206110214510.1016/j.anaerobe.2019.102145 31918362
    [Google Scholar]
  33. MahnicA. AuchtungJ.M. Poklar UlrihN. BrittonR.A. RupnikM. Microbiota in vitro modulated with polyphenols shows decreased colonization resistance against Clostridioides difficile but can neutralize cytotoxicity.Sci. Rep.2020101835810.1038/s41598‑020‑65253‑0 32433519
    [Google Scholar]
  34. ModyD. AthamnehA.I.M. SeleemM.N. Curcumin: A natural derivative with antibacterial activity against Clostridium difficile.J. Glob. Antimicrob. Resist.20202115416110.1016/j.jgar.2019.10.005 31622683
    [Google Scholar]
  35. PellisseryA.J. VinayamohanP.G. KuttappanD.A. Protective Effect of Baicalin against Clostridioides difficile Infection in Mice.Antibiotics202110892610.3390/antibiotics10080926 34438975
    [Google Scholar]
  36. VermaK. MahalapbutrP. SuriyaU. In silico screening of DNA gyrase B potent flavonoids for the treatment of clostridium difficile infection from phytoHub database.Braz. Arch. Biol. Technol.202164e2120040210.1590/1678‑4324‑2021200402
    [Google Scholar]
  37. AzimiradM. NooriM. AzimiradF. Curcumin and capsaicin regulate apoptosis and alleviate intestinal inflammation induced by Clostridioides difficile in vitro.Ann. Clin. Microbiol. Antimicrob.20222114110.1186/s12941‑022‑00533‑3 36155114
    [Google Scholar]
  38. MadkourL.A. Auranofin and Baicalin Inhibit Clostridioides difficile Growth and Sporulation: An In vitro Study.J. Pure Appl. Microbiol.20221631633164210.22207/JPAM.16.3.01
    [Google Scholar]
  39. WuZ. ShenJ. XuQ. Epigallocatechin-3-Gallate Improves Intestinal Gut Microbiota Homeostasis and Ameliorates Clostridioides difficile Infection.Nutrients20221418375610.3390/nu14183756 36145133
    [Google Scholar]
  40. WuZ. XuQ. LiA. LvL. LiL. Apple polyphenol extract suppresses Clostridioides difficile Infection in a mouse model.Metabolites20221211104210.3390/metabo12111042 36355125
    [Google Scholar]
  41. WangW. CaoJ. YangJ. Antimicrobial Activity of Tannic Acid In Vitro and Its Protective Effect on Mice against Clostridioides difficile.Microbiol. Spectr.2023111e02618e0262210.1128/spectrum.02618‑22 36537806
    [Google Scholar]
  42. XieY. FontenotL. EstradaA.C. Genistein inhibits Clostridioides difficile Infection via estrogen receptors and lysine-deficient protein kinase 1.J. Infect. Dis.2023227680681910.1093/infdis/jiad008 36628948
    [Google Scholar]
  43. LeeH.C. JennerA.M. LowC.S. LeeY.K. Effect of tea phenolics and their aromatic fecal bacterial metabolites on intestinal microbiota.Res. Microbiol.2006157987688410.1016/j.resmic.2006.07.004 16962743
    [Google Scholar]
  44. ArfaouiL. Dietary plant polyphenols: effects of food processing on their content and bioavailability.Molecules20212610295910.3390/molecules26102959 34065743
    [Google Scholar]
  45. MakarewiczM. DrożdżI. TarkoT. Duda-ChodakA. The interactions between polyphenols and microorganisms, especially gut microbiota.Antioxidants202110218810.3390/antiox10020188 33525629
    [Google Scholar]
  46. AshwinK. PattanaikA.K. HowarthG.S. Polyphenolic bioactives as an emerging group of nutraceuticals for promotion of gut health: A review.Food Biosci.20214410137610.1016/j.fbio.2021.101376
    [Google Scholar]
  47. WangX. QiY. ZhengH. Dietary polyphenol, gut microbiota, and health benefits.Antioxidants2022116121210.3390/antiox11061212 35740109
    [Google Scholar]
  48. Kumar SinghA. CabralC. KumarR. Beneficial effects of dietary polyphenols on gut microbiota and strategies to improve delivery efficiency.Nutrients2019119221610.3390/nu11092216 31540270
    [Google Scholar]
  49. LiuS. ChengL. LiuY. ZhanS. WuZ. ZhangX. Relationship between dietary polyphenols and gut microbiota: new clues to improve cognitive disorders, mood disorders and circadian rhythms.Foods2023126130910.3390/foods12061309 36981235
    [Google Scholar]
  50. Domínguez-AvilaJ.A. Villa-RodriguezJ.A. Montiel-HerreraM. Phenolic compounds promote diversity of gut microbiota and maintain colonic health.Dig. Dis. Sci.202166103270328910.1007/s10620‑020‑06676‑7 33111173
    [Google Scholar]
  51. PelletierX. Laure-BoussugeS. DonazzoloY. Hydrogen excretion upon ingestion of dairy products in lactose-intolerant male subjects: importance of the live flora.Eur. J. Clin. Nutr.200155650951210.1038/sj.ejcn.1601169 11423928
    [Google Scholar]
  52. Van HulM. CaniP.D. Targeting carbohydrates and polyphenols for a healthy microbiome and healthy weight.Curr. Nutr. Rep.20198430731610.1007/s13668‑019‑00281‑5 31161579
    [Google Scholar]
  53. FengW. AoH. PengC. Gut microbiota, short-chain fatty acids, and herbal medicines.Front. Pharmacol.20189135410.3389/fphar.2018.01354 30532706
    [Google Scholar]
  54. WuZ. HuangS. LiT. Gut microbiota from green tea polyphenol-dosed mice improves intestinal epithelial homeostasis and ameliorates experimental colitis.Microbiome20219118410.1186/s40168‑021‑01115‑9 34493333
    [Google Scholar]
  55. Puupponen-PimiäR. NohynekL. Hartmann-SchmidlinS. Berry phenolics selectively inhibit the growth of intestinal pathogens.J. Appl. Microbiol.2005984991100010.1111/j.1365‑2672.2005.02547.x 15752346
    [Google Scholar]
  56. ZhaoW.H. HuZ.Q. HaraY. ShimamuraT. Inhibition of penicillinase by epigallocatechin gallate resulting in restoration of antibacterial activity of penicillin against penicillinase-producing Staphylococcus aureus.Antimicrob. Agents Chemother.20024672266226810.1128/AAC.46.7.2266‑2268.2002 12069986
    [Google Scholar]
  57. Kowalska-KrochmalB. Dudek-WicherR. The minimum inhibitory concentration of antibiotics: Methods, interpretation, clinical relevance.Pathogens202110216510.3390/pathogens10020165 33557078
    [Google Scholar]
  58. XiaoZ.T. ZhuQ. ZhangH.Y. Identifying antibacterial targets of flavonoids by comparative genomics and molecular modeling.Open J Genom201431810.13055/ojgen_3_1_1.140317
    [Google Scholar]
  59. LouZ. WangH. RaoS. SunJ. MaC. LiJ. p-Coumaric acid kills bacteria through dual damage mechanisms.Food Control201225255055410.1016/j.foodcont.2011.11.022
    [Google Scholar]
  60. DzoyemJ.P. HamamotoH. NgameniB. NgadjuiB.T. SekimizuK. Antimicrobial action mechanism of flavonoids from Dorstenia species.Drug Discov. Ther.2013726672 23715504
    [Google Scholar]
  61. PoxtonI.R. McCoubreyJ. BlairG. The pathogenicity of Clostridium difficile.Clin. Microbiol. Infect.20017842142710.1046/j.1198‑743x.2001.00287.x 11591205
    [Google Scholar]
  62. AbdelKhalekA. AbutalebN.S. MohammadH. SeleemM.N. Antibacterial and antivirulence activities of auranofin against Clostridium difficile.Int. J. Antimicrob. Agents2019531546210.1016/j.ijantimicag.2018.09.018 30273668
    [Google Scholar]
  63. WuX. LiM. XiaoZ. Dietary polyphenols for managing cancers: What have we ignored?Trends Food Sci. Technol.202010115016410.1016/j.tifs.2020.05.017
    [Google Scholar]
  64. CalabrisoN. MassaroM. ScodittiE. CarluccioM.A. Dietary polyphenols and their role in gut health.Nutrients20231512265010.3390/nu15122650 37375554
    [Google Scholar]
  65. TsaoR. Chemistry and biochemistry of dietary polyphenols.Nutrients20102121231124610.3390/nu2121231 22254006
    [Google Scholar]
  66. RastallR.A. GibsonG.R. GillH.S. Modulation of the microbial ecology of the human colon by probiotics, prebiotics and synbiotics to enhance human health: An overview of enabling science and potential applications.FEMS Microbiol. Ecol.200552214515210.1016/j.femsec.2005.01.003 16329901
    [Google Scholar]
  67. FrädrichC. BeerL.A. GerhardR. Reactive oxygen species as additional determinants for cytotoxicity of Clostridium difficile Toxins A and B.Toxins2016812510.3390/toxins8010025 26797634
    [Google Scholar]
  68. Al BanderZ. NitertM.D. MousaA. NaderpoorN. The gut microbiota and inflammation: An overview.Int. J. Environ. Res. Public Health20201720761810.3390/ijerph17207618 33086688
    [Google Scholar]
  69. ChimentoA. De LucaA. D’AmicoM. De AmicisF. PezziV. The involvement of natural polyphenols in molecular mechanisms inducing apoptosis in tumor cells: A promising adjuvant in cancer therapy.Int. J. Mol. Sci.2023242168010.3390/ijms24021680 36675194
    [Google Scholar]
  70. NaoiM. WuY. Shamoto-NagaiM. MaruyamaW. Mitochondria in neuroprotection by phytochemicals: Bioactive polyphenols modulate mitochondrial apoptosis system, function and structure.Int. J. Mol. Sci.20192010245110.3390/ijms20102451 31108962
    [Google Scholar]
  71. Morales-GonzálezJ.A. Soriano-UrsúaM.A. Rodríguez-VeraD. Polyphenols as potential enhancers of stem cell therapy against neurodegeneration.Neural Regen. Res.202217102093210110.4103/1673‑5374.335826 35259814
    [Google Scholar]
  72. VestbyL.K. GrønsethT. SimmR. NesseL.L. Bacterial biofilm and its role in the pathogenesis of disease.Antibiotics2020925910.3390/antibiotics9020059 32028684
    [Google Scholar]
  73. SlobodníkováL. FialováS. RendekováK. KováčJ. MučajiP. Antibiofilm activity of plant polyphenols.Molecules20162112171710.3390/molecules21121717 27983597
    [Google Scholar]
  74. BarbieriR. CoppoE. MarcheseA. Phytochemicals for human disease: An update on plant-derived compounds antibacterial activity.Microbiol. Res.2017196446810.1016/j.micres.2016.12.003 28164790
    [Google Scholar]
  75. ShindeS. LeeL.H. ChuT. Inhibition of biofilm formation by the synergistic action of egcg-s and antibiotics.Antibiotics202110210210.3390/antibiotics10020102 33494273
    [Google Scholar]
  76. FrostL.R. ChengJ.K.J. UnnikrishnanM. Clostridioides difficile biofilms: A mechanism of persistence in the gut?PLoS Pathog.2021173e100934810.1371/journal.ppat.1009348 33705497
    [Google Scholar]
  77. MarínL. MiguélezE.M. VillarC.J. LombóF. Bioavailability of dietary polyphenols and gut microbiota metabolism: antimicrobial properties.BioMed Res. Int.2015201511810.1155/2015/905215 25802870
    [Google Scholar]
  78. UlreyR.K. BarksdaleS.M. ZhouW. van HoekM.L. Cranberry proanthocyanidins have anti-biofilm properties against Pseudomonas aeruginosa.BMC Complement. Altern. Med.201414149910.1186/1472‑6882‑14‑499 25511463
    [Google Scholar]
  79. IvanovM. NovovićK. MaleševićM. Polyphenols as inhibitors of antibiotic resistant bacteria—mechanisms underlying rutin interference with bacterial virulence.Pharmaceuticals (Basel)202215338510.3390/ph15030385 35337182
    [Google Scholar]
  80. ShivashankaraK.S. AcharyaS.N. Bioavailability of dietary polyphenols and the cardiovascular diseases.Open Nutraceuticals J.20103122724110.2174/1876396001003010227
    [Google Scholar]
  81. BohnT. Dietary factors affecting polyphenol bioavailability.Nutr. Rev.201472742945210.1111/nure.12114 24828476
    [Google Scholar]
  82. D’ArchivioM. FilesiC. VarìR. ScazzocchioB. MasellaR. Bioavailability of the polyphenols: status and controversies.Int. J. Mol. Sci.20101141321134210.3390/ijms11041321 20480022
    [Google Scholar]
  83. BiéJ. SepodesB. FernandesP.C.B. RibeiroM.H.L. Polyphenols in health and disease: Gut microbiota, bioaccessibility, and bioavailability.Compounds202331407210.3390/compounds3010005
    [Google Scholar]
  84. GowdV. KarimN. ShishirM.R.I. XieL. ChenW. Dietary polyphenols to combat the metabolic diseases via altering gut microbiota.Trends Food Sci. Technol.201993819310.1016/j.tifs.2019.09.005
    [Google Scholar]
  85. CrozierA. Del RioD. CliffordM.N. Bioavailability of dietary flavonoids and phenolic compounds.Mol. Aspects Med.201031644646710.1016/j.mam.2010.09.007 20854839
    [Google Scholar]
  86. AatifM. Current Understanding of Polyphenols to Enhance Bioavailability for Better Therapies.Biomedicines2023117207810.3390/biomedicines11072078 37509717
    [Google Scholar]
  87. Duda-ChodakA. TarkoT. Possible side effects of polyphenols and their interactions with medicines.Molecules2023286253610.3390/molecules28062536 36985507
    [Google Scholar]
  88. NguyenR.H.N. UmbachD.M. ParadR.B. StroehlaB. RoganW.J. EstroffJ.A. US assessment of estrogen-responsive organ growth among healthy term infants: piloting methods for assessing estrogenic activity.Pediatr. Radiol.201141563364210.1007/s00247‑010‑1895‑0 21104239
    [Google Scholar]
  89. HurrellR. EgliI. Iron bioavailability and dietary reference values.Am. J. Clin. Nutr.20109151461S1467S10.3945/ajcn.2010.28674F 20200263
    [Google Scholar]
  90. ZhangH. TsaoR. Dietary polyphenols, oxidative stress and antioxidant and anti-inflammatory effects.Curr. Opin. Food Sci.20168334210.1016/j.cofs.2016.02.002
    [Google Scholar]
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