Managing Helicobacter pylori infection: transitioning from conventional to alternative treatment approaches

Year 2024, Volume: 10 Issue: 1 - January 2024, 136 - 143, 04.01.2024

Serhat Öcal

https://doi.org/10.18621/eurj.1320819

Abstract

Helicobacter pylori, an essential constituent of the gastric microbiome in those infected, is commonly associated with medical conditions such as chronic gastritis, peptic ulcer disease, and gastric cancer. In recent years, the growing resistance to antibiotics worldwide has emerged as a substantial hurdle in the effective treatment of H. pylori infection. Consequently, it has necessitated the exploration of innovative treatment strategies aimed at bolstering the potency of existing antibiotic-based eradication therapies. Such avant-garde strategies include the incorporation of probiotics and prebiotics as complementary measures to H. pylori treatment, the use of antimicrobial peptides as potential replacements for traditional antibiotics, and the application of photodynamic therapy via ingestible devices. Other advanced methodologies entail deploying drug delivery systems that utilize microparticles and nanoparticles, the invention of vaccines, the exploration of natural products, and the potential use of phage therapy. This review offers a contemporary synopsis of these burgeoning strategies designed to suppress H. pylori, delving into their strengths, hurdles, and aspects to consider during their development. A significant achievement would be the creation of an efficient human vaccine; however, previous attempts at developing such vaccines have met with obstacles or even cessation. Numerous natural products have displayed anti-H. pylori properties, predominantly in laboratory environments. Nonetheless, a requirement remains for more extensive clinical studies to fully comprehend their role in exterminating H. pylori. Finally, phage therapy, while demonstrating potential as a suitable alternative, grapples with considerable challenges, chiefly the isolation of highly virulent bacteriophages that specifically target H. pylori.

Keywords

Helicobacter pylori, antibiotic resistance, innovative treatment strategies

References

• 1. Azevedo NF, Pinto AR, Reis NM, Vieira MJ, Keevil CW. Shear stress, temperature, and inoculation concentration influence the adhesion of water-stressed Helicobacter pylori to stainless steel 304 and polypropylene. Appl Environ Microbiol. 2006;72(4):2936-2941. doi: 10.1128/AEM.72.4.2936-2941.2006.
• 2. Hooi JKY, Lai WY, Ng WK, et al. Global Prevalence of Helicobacter pylori Infection: Systematic Review and Meta-Analysis. Gastroenterology. 2017;153(2):420-429. doi: 10.1053/j.gastro.2017.04.022.
• 3. Bik EM, Eckburg PB, Gill SR, et al. Molecular analysis of the bacterial microbiota in the human stomach. Proc Natl Acad Sci U S A. 2006;103(3):732-737. doi: 10.1073/pnas.0506655103.
• 4. Klymiuk I, Bilgilier C, Stadlmann A, Thannesberger J, et al. The Human Gastric Microbiome Is Predicated upon Infection with Helicobacter pylori. Front Microbiol. 2017;8:2508. doi: 10.3389/fmicb.2017.02508.
• 5. Parsons BN, Ijaz UZ, D'Amore R, et al. Comparison of the human gastric microbiota in hypochlorhydric states arising as a result of Helicobacter pylori-induced atrophic gastritis, autoimmune atrophic gastritis and proton pump inhibitor use. PLoS Pathog. 2017;13(11):e1006653. doi: 10.1371/journal.ppat.1006653.
• 6. Wang Z, Bafadhel M, Haldar K, et al. Lung microbiome dynamics in COPD exacerbations. Eur Respir J. 2016;47(4):1082-1092. doi: 10.1183/13993003.01406-2015.
• 7. Ferreira RM, Pereira-Marques J, Pinto-Ribeiro I, et al. Gastric microbial community profiling reveals a dysbiotic cancer-associated microbiota. Gut. 2018;67(2):226-236. doi: 10.1136/gutjnl-2017-314205.
• 8. Cover TL, Blaser MJ. Helicobacter pylori in health and disease. Gastroenterology. 2009;136(6):1863-1873. doi: 10.1053/j.gastro.2009.01.073.
• 9. Gerhard M, Rad R, Prinz C, Naumann M. Pathogenesis of Helicobacter pylori infection. Helicobacter. 2002;7 Suppl 1:17-23. doi: 10.1046/j.1523-5378.7.s1.3.x.
• 10. Blaser MJ. Helicobacter pylori and the pathogenesis of gastroduodenal inflammation. J Infect Dis. 1990;161(4):626-633. doi: 10.1093/infdis/161.4.626.
• 11. Ferreira RM, Machado JC, Figueiredo C. Clinical relevance of Helicobacter pylori vacA and cagA genotypes in gastric carcinoma. Best Pract Res Clin Gastroenterol. 2014;28(6):1003-1015. doi: 10.1016/j.bpg.2014.09.004.
• 12. Franceschi F, Annalisa T, Teresa DR, et al. Role of Helicobacter pylori infection on nutrition and metabolism. World J Gastroenterol. 2014;20(36):12809-12817. doi: 10.3748/wjg.v20.i36.12809.
• 13. Liou JM, Chen CC, Chen MJ. Sequential versus triple therapy for the first-line treatment of Helicobacter pylori: a multicentre, open-label, randomised trial. Lancet. 2013;381(9862):205-213. doi: 10.1016/S0140-6736(12)61579-7.
• 14. Tai WC, Liang CM, Kuo CM, et al. A 14 day esomeprazole- and amoxicillin-containing high-dose dual therapy regimen achieves a high eradication rate as first-line anti-Helicobacter pylori treatment in Taiwan: a prospective randomized trial. J Antimicrob Chemother. 2019;74(6):1718-1724. doi: 10.1093/jac/dkz046.
• 15. Hsu PI, Wu DC, Chen WC, et al. Randomized controlled trial comparing 7-day triple, 10-day sequential, and 7-day concomitant therapies for Helicobacter pylori infection. Antimicrob Agents Chemother. 2014;58(10):5936-5942. doi: 10.1128/AAC.02922-14.
• 16. Hanada K, Graham DY. Helicobacter pylori and the molecular pathogenesis of intestinal-type gastric carcinoma. Expert Rev Anticancer Ther. 2014;14(8):947-954. doi: 10.1586/14737140.2014.911092.
• 17. Fallone CA, Chiba N, van Zanten SV, et al. The Toronto Consensus for the Treatment of Helicobacter pylori Infection in Adults. Gastroenterology. 2016;151(1):51-69. doi: 10.1053/j.gastro.2016.04.006.
• 18. Malfertheiner P, Megraud F, O'Morain CA, et al. Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report. Gut. 2017;66(1):6-30. doi: 10.1136/gutjnl-2016-312288.
• 19. Molina-Infante J, Romano M, Fernandez-Bermejo M, et al. Optimized nonbismuth quadruple therapies cure most patients with Helicobacter pylori infection in populations with high rates of antibiotic resistance. Gastroenterology. 2013;145(1):121-128. doi: 10.1053/j.gastro.2013.03.050.
• 20. Li M, Oshima T, Horikawa T, Tozawa K, Tomita T, Fukui H, Watari J, Miwa H. Systematic review with meta-analysis: Vonoprazan, a potent acid blocker, is superior to proton-pump inhibitors for eradication of clarithromycin-resistant strains of Helicobacter pylori. Helicobacter. 2018;23(4):e12495. doi: 10.1111/hel.12495.
• 21. Guevara B, Cogdill AG. Helicobacter pylori: A Review of Current Diagnostic and Management Strategies. Dig Dis Sci. 2020;65(7):1917-1931. doi: 10.1007/s10620-020-06193-7.
• 22. Gisbert JP, Romano M, Gravina AG, et al. Helicobacter pylori second-line rescue therapy with levofloxacin- and bismuth-containing quadruple therapy, after failure of standard triple or non-bismuth quadruple treatments. Aliment Pharmacol Ther. 2015;41(8):768-775. doi: 10.1111/apt.13128.
• 23. Murakami K, Sakurai Y, Shiino M, Funao N, Nishimura A, Asaka M. Vonoprazan, a novel potassium-competitive acid blocker, as a component of first-line and second-line triple therapy for Helicobacter pylori eradication: a phase III, randomised, double-blind study. Gut. 2016;65(9):1439-1446. doi: 10.1136/gutjnl-2015-311304.
• 24. Suzuki S, Gotoda T, Kusano C, Iwatsuka K, Moriyama M. The Efficacy and Tolerability of a Triple Therapy Containing a Potassium-Competitive Acid Blocker Compared With a 7-Day PPI-Based Low-Dose Clarithromycin Triple Therapy. Am J Gastroenterol. 2016;111(7):949-956. doi: 10.1038/ajg.2016.182.
• 25. Gatta L, Vakil N, Vaira D, Scarpignato C. Global eradication rates for Helicobacter pylori infection: systematic review and meta-analysis of sequential therapy. BMJ. 2013;347:f4587. doi: 10.1136/bmj.f4587.
• 26. O'Morain NR, Dore MP, O'Connor AJP, Gisbert JP, O'Morain CA. Treatment of Helicobacter pylori infection in 2018. Helicobacter. 2018;23 Suppl 1:e12519. doi: 10.1111/hel.12519.
• 27. Savoldi A, Carrara E, Graham DY, Conti M, Tacconelli E. Prevalence of Antibiotic Resistance in Helicobacter pylori: A Systematic Review and Meta-analysis in World Health Organization Regions. Gastroenterology. 2018;155(5):1372-1382. doi: 10.1053/j.gastro.2018.07.007.
• 28. Megraud F, Coenen S, Versporten A, et al. Helicobacter pylori resistance to antibiotics in Europe and its relationship to antibiotic consumption. Gut. 2013;62(1):34-42. doi: 10.1136/gutjnl-2012-302254.
• 29. Savoldi A, Carrara E, Graham DY, Conti M, Tacconelli E. Prevalence of Antibiotic Resistance in Helicobacter pylori: A Systematic Review and Meta-analysis in World Health Organization Regions. Gastroenterology. 2018;155(5):1372-1382. doi: 10.1053/j.gastro.2018.07.007.
• 30. Malfertheiner P, Megraud F, O'Morain C, et al. Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report. Gut. 2007;56(6):772-781. doi: 10.1136/gut.2006.101634.
• 31. Hill C, Guarner F, Reid G, et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11(8):506-514. doi: 10.1038/nrgastro.2014.66.
• 32. Davani-Davari D, Negahdaripour M, Karimzadeh I, et al. Prebiotics: Definition, Types, Sources, Mechanisms, and Clinical Applications. Foods. 2019;8(3):92. doi: 10.3390/foods8030092.
• 33. Ahmad K, Fatemeh F, Mehri N, Maryam S. Probiotics for the treatment of pediatric helicobacter pylori infection: a randomized double blind clinical trial. Iran J Pediatr. 2013;23(1):79-84.
• 34. Lionetti E, Miniello VL, Castellaneta SP, et al. Lactobacillus reuteri therapy to reduce side-effects during anti-Helicobacter pylori treatment in children: a randomized placebo controlled trial. Aliment Pharmacol Ther. 2006;24(10):1461-1468. doi: 10.1111/j.1365-2036.2006.03145.x.
• 35. Sgouras DN, Panayotopoulou EG, Martinez-Gonzalez B, Petraki K, Michopoulos S, Mentis A. Lactobacillus johnsonii La1 attenuates Helicobacter pylori-associated gastritis and reduces levels of proinflammatory chemokines in C57BL/6 mice. Clin Diagn Lab Immunol. 2005;12(12):1378-1386. doi: 10.1128/CDLI.12.12.1378-1386.2005.
• 36. Kulkarni T, Majarikar S, Deshmukh M, et al. Probiotic sepsis in preterm neonates-a systematic review. Eur J Pediatr. 2022;181(6):2249-2262. doi: 10.1007/s00431-022-04452-5.
• 37. Joshi A, Agrawal A, Bhattacharya S. Formulation and clinical advancement of nanourchins: a novel multibranched nanoparticulate drug-delivery system. Nanomedicine (Lond). 2022;17(20):1477-1499. doi: 10.2217/nnm-2022-0096.
• 38. Luong AD, Buzid A, Luong JHT. Important Roles and Potential Uses of Natural and Synthetic Antimicrobial Peptides (AMPs) in Oral Diseases: Cavity, Periodontal Disease, and Thrush. J Funct Biomater. 2022;13(4):175. doi: 10.3390/jfb13040175.
• 39. Gao JH, Guo LJ, Huang ZY, Rao JN, Tang CW. Roles of cellular polyamines in mucosal healing in the gastrointestinal tract. J Physiol Pharmacol. 2013;64(6):681-693.
• 40. Ruan Q, Guan P, Qi W, et al. Porphyromonas gingivalis regulates atherosclerosis through an immune pathway. Front Immunol. 2023;14:1103592. doi: 10.3389/fimmu.2023.1103592.
• 41. Park SC, Park Y, Hahm KS. The role of antimicrobial peptides in preventing multidrug-resistant bacterial infections and biofilm formation. Int J Mol Sci. 2011;12(9):5971-5992. doi: 10.3390/ijms12095971.
• 42. Jungersen M, Wind A, Johansen E, Christensen JE, Stuer-Lauridsen B, Eskesen D. The Science behind the Probiotic Strain Bifidobacterium animalis subsp. lactis BB-12(®). Microorganisms. 2014;2(2):92-110. doi: 10.3390/microorganisms2020092.
• 43. Michalak A, Kasztelan-Szczerbińska B, Cichoż-Lach H. Impact of Obesity on the Course of Management of Inflammatory Bowel Disease-A Review. Nutrients. 2022;14(19):3983. doi: 10.3390/nu14193983.
• 44. Zhang MM, Qian W, Qin YY, He J, Zhou YH. Probiotics in Helicobacter pylori eradication therapy: a systematic review and meta-analysis. World J Gastroenterol. 2015;21(14):4345-4357. doi: 10.3748/wjg.v21.i14.4345.
• 45. McFarland LV, Huang Y, Wang L, Malfertheiner P. Systematic review and meta-analysis: Multi-strain probiotics as adjunct therapy for Helicobacter pylori eradication and prevention of adverse events. United European Gastroenterol J. 2016;4(4):546-561. doi: 10.1177/2050640615617358.
• 46. Milner E, Stevens B, An M, et al. Utilizing Probiotics for the Prevention and Treatment of Gastrointestinal Diseases. Front Microbiol. 2021;12:689958. doi: 10.3389/fmicb.2021.689958.
• 47. Ji J, Yang H. Using Probiotics as Supplementation for Helicobacter pylori Antibiotic Therapy. Int J Mol Sci. 2020;21(3):1136. doi: 10.3390/ijms21031136.
• 48. Igarashi M, Kitada Y, Yoshiyama H, Takagi A, Miwa T, Koga Y. Ammonia as an accelerator of tumor necrosis factor alpha-induced apoptosis of gastric epithelial cells in Helicobacter pylori infection. Infect Immun. 2001;69(2):816-821. doi: 10.1128/IAI.69.2.816-821.2001.
• 49. Guzmán-Rodríguez JJ, López-Gómez R, Suárez-Rodríguez LM, et al. Antibacterial activity of defensin PaDef from avocado fruit (Persea americana var. drymifolia) expressed in endothelial cells against Escherichia coli and Staphylococcus aureus. Biomed Res Int. 2013;2013:986273. doi: 10.1155/2013/986273.
• 50.Foligne B, Nutten S, Grangette C, Dennin V, et al. Correlation between in vitro and in vivo immunomodulatory properties of lactic acid bacteria. World J Gastroenterol. 2007;13(2):236-243. doi: 10.3748/wjg.v13.i2.236.
• 51. Hamblin MR, Hasan T. Photodynamic therapy: a new antimicrobial approach to infectious disease? Photochem Photobiol Sci. 2004;3(5):436-450. doi: 10.1039/b311900a.
• 52. Sokic-Milutinovic A, Todorovic V, Milosavljevic T, Micev M, Drndarevic N, Mitrovic O. Gastrin and antral G cells in course of Helicobacter pylori eradication: six months follow up study. World J Gastroenterol. 2005;11(27):4140-4147. doi: 10.3748/wjg.v11.i27.4140.
• 53. Kellesarian SV, Malignaggi VR, Al-Kheraif AA, Al-Askar M, Yunker M, Javed F. Effect of antimicrobial photodynamic therapy and laser alone as adjunct to mechanical debridement in the management of halitosis: A systematic review. Quintessence Int. 2017;48(7):575-583. doi: 10.3290/j.qi.a38264.
• 54. Calvino-Fernández M, García-Fresnadillo D, Benito-Martínez S, et al. Helicobacter pylori inactivation and virulence gene damage using a supported sensitiser for photodynamic therapy. Eur J Med Chem. 2013;68:284-290. doi: 10.1016/j.ejmech.2013.07.023.
• 55. Denis TGS, Hamblin MR. An introduction to photoantimicrobials: photodynamic therapy as a novel method of microbial pathogen eradication. In: Méndez-Vilas A, ed., Science against microbial pathogens: communicating current research and technological advances. Microbiology Series. No:3., Badajoz, Spain: Formatex, 2011: pp. 675-683.
• 56. Wilder-Smith CH, Wilder-Smith P, Grosjean P, et al. Photoeradication of Helicobacter pylori using 5-aminolevulinic acid: preliminary human studies. Lasers Surg Med. 2002;31(1):18-22. doi: 10.1002/lsm.10066.
• 57. Aguilera-Correa JJ, Esteban J, Vallet-Regí M. Inorganic and Polymeric Nanoparticles for Human Viral and Bacterial Infections Prevention and Treatment. Nanomaterials (Basel). 2021;11(1):137. doi: 10.3390/nano11010137.
• 58. Xiong MH, Bao Y, Yang XZ, Zhu YH, Wang J. Delivery of antibiotics with polymeric particles. Adv Drug Deliv Rev. 2014;78:63-76. doi: 10.1016/j.addr.2014.02.002.
• 59. Matricardi P, Meo CD, Coviello T, Alhaique F. Recent advances and perspectives on coated alginate microspheres for modified drug delivery. Expert Opin Drug Deliv. 2008;5(4):417-425. doi: 10.1517/17425247.5.4.417.
• 60. Malaekeh-Nikouei B, Bazzaz BSF, Mirhadi E, Tajani AS, Khameneh B. The role of nanotechnology in combating biofilm-based antibiotic resistance. J Drug Deliv Sci Technol 2020;60:101880. doi:10.1016/j.jddst.2020.101880
• 61. Mehta DK, Rai SR. Microencapsulation of Lactobacillus acidophilus NCDC 291 using emulsion technique and sensory and physico-chemical analysis of the incorporated microcapsules in dairy and non-dairy food product. In: Singhee D, Bhattacharyya K, Tuteja S, Sarkar A. eds., Reflections. JD Birla Institute: Kolkota (West Bengal), India, 2017: pp. 51-57.
• 62. Liang J, Yan H, Puligundla P, Gao X, Zhou Y, Wan X. Applications of chitosan nanoparticles to enhance absorption and bioavailability of tea polyphenols: a review. Food Hydrocoll 2017;69:286-292. doi:10.1016/j.foodhyd.2017.01.041
• 63. Gupta R, Prasad Y. Efficacy of polyvalent bacteriophage P-27/HP to control multidrug resistant Staphylococcus aureus associated with human infections. Curr Microbiol. 2011;62(1):255-260. doi: 10.1007/s00284-010-9699-x.
• 64. de Bortoli N, Leonardi G, Ciancia E, et al. Helicobacter pylori eradication: a randomized prospective study of triple therapy versus triple therapy plus lactoferrin and probiotics. Am J Gastroenterol. 2007;102(5):951-956. doi: 10.1111/j.1572-0241.2007.01085.x.
• 65. Malfertheiner P, Selgrad M, Bornschein J. Helicobacter pylori: clinical management. Curr Opin Gastroenterol. 2012;28(6):608-14. doi: 10.1097/MOG.0b013e32835918a7.
• 66. Dar HA, Zaheer T, Shehroz M, et al. Immunoinformatics-Aided Design and Evaluation of a Potential Multi-Epitope Vaccine against Klebsiella Pneumoniae. Vaccines (Basel). 2019;7(3):88. doi: 10.3390/vaccines7030088.
• 67. Chen Y, Hu H, Huang F, et al. Cocktail of isobavachalcone and curcumin enhance eradication of Staphylococcus aureus biofilm from orthopedic implants by gentamicin and alleviate inflammatory osteolysis. Front Microbiol. 2022;13:958132. doi: 10.3389/fmicb.2022.958132.
• 68. Abd Eldaim MA, Tousson E, Soliman MM, El Sayed IET, Abdel Aleem AAH, Elsharkawy HN. Grape seed extract ameliorated Ehrlich solid tumor-induced hepatic tissue and DNA damage with reduction of PCNA and P53 protein expression in mice. Environ Sci Pollut Res Int. 2021;28(32):44226-44238. doi: 10.1007/s11356-021-13904-8.
• 69. Muhammad SNH, Yaacob NS, Safuwan NAM, Fauzi AN. Antiglycolytic Activities of Strobilanthes crispus Active Fraction and its Bioactive Components on Triple-Negative Breast Cancer Cells In Vitro. Anticancer Agents Med Chem. 2022;22(7):1363-1369. doi: 10.2174/1871520621666210427104804.
• 70. Nzeako BC, Al-Namaani F. The antibacterial activity of honey on helicobacter pylori. Sultan Qaboos Univ Med J. 2006 Dec;6(2):71-76.
• 71. Viertel TM, Ritter K, Horz HP. Viruses versus bacteria-novel approaches to phage therapy as a tool against multidrug-resistant pathogens. J Antimicrob Chemother. 2014;69(9):2326-2336. doi: 10.1093/jac/dku173.
• 72. Casey E, van Sinderen D, Mahony J. In Vitro Characteristics of Phages to Guide 'Real Life' Phage Therapy Suitability. Viruses. 2018;10(4):163. doi: 10.3390/v10040163.
• 73. Uyttebroek S, Chen B, Onsea J. Safety and efficacy of phage therapy in difficult-to-treat infections: a systematic review. Lancet Infect Dis. 2022;22(8):e208-e220. doi: 10.1016/S1473-3099(21)00612-5.
• 74. Sousa C, Ferreira R, Azevedo NF, et al. Helicobacter pylori infection: from standard to alternative treatment strategies. Crit Rev Microbiol. 2022;48(3):376-396. doi: 10.1080/1040841X.2021.1975643.
• 75. Galtier M, De Sordi L, Maura D, et al. Bacteriophages to reduce gut carriage of antibiotic resistant uropathogens with low impact on microbiota composition. Environ Microbiol. 2016;18(7):2237-2245. doi: 10.1111/1462-2920.13284.
• 76. Elbehiry A, Marzouk E, Aldubaib M, et al. Helicobacter pylori Infection: Current Status and Future Prospects on Diagnostic, Therapeutic and Control Challenges. Antibiotics (Basel). 2023;12(2):191. doi: 10.3390/antibiotics12020191.
• 77. Oliveira H, Thiagarajan V, Walmagh M, et al. A thermostable Salmonella phage endolysin, Lys68, with broad bactericidal properties against gram-negative pathogens in presence of weak acids. PLoS One. 2014;9(10):e108376. doi: 10.1371/journal.pone.0108376.
• 78. Oliveira H, Melo LD, Santos SB, et al. Molecular aspects and comparative genomics of bacteriophage endolysins. J Virol. 2013;87(8):4558-4570. doi: 10.1128/JVI.03277-12.
• 79. Oliveira H, São-José C, Azeredo J. Phage-Derived Peptidoglycan Degrading Enzymes: Challenges and Future Prospects for In Vivo Therapy. Viruses. 2018;10(6):292. doi: 10.3390/v10060292.
• 80. Lukacik P, Barnard TJ, Keller PW, et al. Structural engineering of a phage lysin that targets gram-negative pathogens. Proc Natl Acad Sci U S A. 2012;109(25):9857-9862. doi: 10.1073/pnas.1203472109.
• 81. Lood R, Winer BY, Pelzek AJ, et al. Novel phage lysin capable of killing the multidrug-resistant gram-negative bacterium Acinetobacter baumannii in a mouse bacteremia model. Antimicrob Agents Chemother. 2015;59(4):1983-1991. doi: 10.1128/AAC.04641-14.