Exploring the Gut Microbiome's Influence on Peptic Ulcer Disease: Mechanistic Insights, Pharmacological Implications, and Emerging Therapeutic Strategies
Abstract
Background: The gastrointestinal disorder Peptic Ulcer Disease (PUD) leads to mucosal damage in either stomach or duodenal tissue because of acid-peptic injury. The available evidence demonstrates that Helicobacter pylori (H. pylori) infection and nonsteroidal anti-inflammatory drug (NSAID) usage serve as proven ulcer causes but new research shows the gut microbiome as contributing to ulcer development and therapeutic approaches.
Objective: The purpose of this section is to examine the standard H. pylori ulcer development process while examining host immune responses through gut microbial alterations and their effect on PUD disease progression.
Methods: This study reviewed multiple research articles to examine how bacteria affect epithelial cells while studying inflammatory pathways as well as microbial metabolites particularly short-chain fatty acids (SCFAs). The review examined different pharmacy-based and natural therapies from the perspective of their ability to modulate the microbiome.
Results: The research shows Non-H. Pylori bacteria damage gastric mucosal tissue by activating pro-inflammatory cytokines which leads to gastric homeostasis disturbances because of SCFA production. The ulcer formation gets worse because dysbiosis makes the intestines more sensitive to oxidative stress while simultaneously making the protective mucosal layer weaker. Antibiotics together with proton pump inhibitors affect gut microbial composition but natural treatments including curcumin combined with ginger and probiotics both contribute to microbial recovery and healing of ulcers.
Conclusion: Previous research about the gut microbiome's role in PUD pathogenesis forms a base for future development of tailored therapeutic strategies. Combining microbiome-based therapeutic methods with traditional medical protocols produces better management strategies for ulcers with improved healthcare results for patients.
Keywords:Peptic Ulcer Disease, Gut Microbiota, Microbial Dysbiosis, Immunoglobulin A (IgA), Gastrointestinal Inflammation, Mucosal Homeostasis
Keywords:
Peptic Ulcer Disease, Gut Microbiota, Microbial Dysbiosis, Immunoglobulin A (IgA), Gastrointestinal Inflammation, Mucosal HomeostasisDOI
https://doi.org/10.22270/jddt.v15i4.7088References
1. Harsha C, Banik K, Bordoloi D, Kunnumakkara AB. Antiulcer properties of fruits and vegetables: A mechanism based perspective. Food and Chemical Toxicology, 2017; 108:104-119. https://doi.org/10.1016/j.fct.2017.07.023
2. Smith ME, Morton DG. The stomach. In: The Digestive System. 2nd ed. Elsevier; 2010:51-69. https://doi.org/10.1016/B978-0-7020-3367-4.00004-9
3. Wallace JL. Recent advances in gastric ulcer therapeutics. Current Opinion in Pharmacology, 2005; 5(6):573-577. https://doi.org/10.1016/j.coph.2005.06.004
4. Malik TF, Gnanapandithan K, Singh K. Peptic ulcer disease. In: Helicobacter pylori. Springer; 2023:635-639. https://doi.org/10.1007/978-981-97-0013-4-54
5. Malfertheiner P, Mégraud 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. https://doi.org/10.1136/gut.2006.101634
6. Elbehiry A, Marzouk E, Aldubaib M, et al. Helicobacter pylori infection: Current status and future prospects on diagnostic, therapeutic and control challenges. Antibiotics, 2023; 12(2):191. https://doi.org/10.3390/antibiotics12020191
7. 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. https://doi.org/10.1053/j.gastro.2017.04.022
8. Kayali S, Manfredi M, Gaiani F, et al. Helicobacter pylori, transmission routes and recurrence of infection: State of the art. Acta Biomedica, 2018; 89:72-76. https://doi.org/10.23750/abm.v89i8-s.7947
9. Parikh NS, Ahlawat R. Helicobacter pylori. StatPearls. Published online August 8, 2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK534233/
10. Schloss PD, Handelsman J. Status of the microbial census. Microbiology and Molecular Biology Reviews, 2004; 68(4):686-691. https://doi.org/10.1128/MMBR.68.4.686-691.2004
11. Bull MJ, Plummer NT. Part 1: The human gut microbiome in health and disease. Integrative Medicine: A Clinician's Journal, 2014; 13(6):17. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC4566439/
12. Oami T, Chihade DB, Coopersmith CM. The microbiome and nutrition in critical illness. Current Opinion in Critical Care, 2019; 25(2):145-149. https://doi.org/10.1097/MCC.0000000000000582
13. Leonard JM, Del Toro D. Defining the microbiome components (bacteria, viruses, fungi) and microbiome geodiversity. Surgical Infections, 2023; 24(3):208. https://doi.org/10.1089/sur.2023.014
14. Ley RE, Peterson DA, Gordon JI. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell, 2006; 124(4):837-848. https://doi.org/10.1016/j.cell.2006.02.017
15. Mazmanian SK, Kasper DL. The love-hate relationship between bacterial polysaccharides and the host immune system. Nature Reviews Immunology, 2006; 6(11):849-858. https://doi.org/10.1038/nri1956
16. Dethlefsen L, McFall-Ngai M, Relman DA. An ecological and evolutionary perspective on human-microbe mutualism and disease. Nature, 2007; 449(7164):811-818. https://doi.org/10.1038/nature06245
17. Round JL, Mazmanian SK. The gut microbiome shapes intestinal immune responses during health and disease. Nature Reviews Immunology, 2009; 9(5):313. https://doi.org/10.1038/nri2515
18. Akin OY, Tsou VM, Werner AL. Gastrospirillum hominis-associated chronic active gastritis. Fetal and Pediatric Pathology, 1995; 15(3):429-435. https://doi.org/10.3109/15513819509026978
19. Akada JK, Shirai M, Takeuchi H, Tsuda M, Nakazawa T. Identification of the urease operon in Helicobacter pylori and its control by mRNA decay in response to pH. Molecular Microbiology, 2000; 36(5):1071-1084. https://doi.org/10.1046/j.1365-2958.2000.01918.x
20. Akhiani AA, Pappo J, Kabok Z, et al. Protection against Helicobacter pylori infection following immunization is IL-12-dependent and mediated by Th1 cells. Journal of Immunology, 2002; 169(12):6977-6984. https://doi.org/10.4049/jimmunol.169.12.6977
21. Kusters JG, Van Vliet AHM, Kuipers EJ. Pathogenesis of Helicobacter pylori infection. Clinical Microbiology Reviews, 2006; 19(3):449-490. https://doi.org/10.1128/CMR.00054-05
22. Achtman M, Suerbaum S. Sequence variation in Helicobacter pylori. Trends in Microbiology, 2000; 8(2):57-58. https://doi.org/10.1016/S0966-842X(99)01676-5
23. Ferlay J, Colombet M, Soerjomataram I, et al. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. International Journal of Cancer, 2019; 144(8):1941-1953. https://doi.org/10.1002/ijc.31937
24. Reyes VE. Helicobacter pylori and its role in gastric cancer. Microorganisms, 2023; 11(5):1312. https://doi.org/10.3390/microorganisms11051312
25. Kurilshikov A, Medina-Gomez C, Bacigalupe R, et al. Large-scale association analyses identify host factors influencing human gut microbiome composition. Nature Genetics, 2021; 53(2):156-165. https://doi.org/10.1038/s41588-020-00763-1
26. Zhao JH, Stacey D, Eriksson N, et al. Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets. Nature Immunology, 2023; 24(9):1540-1551. https://doi.org/10.1038/s41590-023-01588-w
27. He Y, Koido M, Sutoh Y, et al. East Asian-specific and cross-ancestry genome-wide meta-analyses provide mechanistic insights into peptic ulcer disease. Nature Genetics, 2023; 55(12):2129-2138. https://doi.org/10.1038/s41588-023-01569-7
28. Mujadzic H, Noorani S, Riddle PJ, et al. Ulcer bleeding in the United States: Epidemiology, treatment success, and resource utilization. Digestive Diseases and Sciences, 2024; 69(6):1963-1971. https://doi.org/10.1007/s10620-024-08322-y
29. Li W, Lv BM, Quan Y, Zhu Q, Zhang HY. Associations between serum mineral nutrients, gut microbiota, and risk of neurological, psychiatric, and metabolic diseases: A comprehensive Mendelian randomization study. Nutrients, 2024; 16(2):244. https://doi.org/10.3390/nu16020244
30. Sanders ME, Merenstein DJ, Reid G, Gibson GR, Rastall RA. Probiotics and prebiotics in intestinal health and disease: From biology to the clinic. Nature Reviews Gastroenterology & Hepatology, 2019; 16(10):605-616. https://doi.org/10.1038/s41575-019-0173-3
31. Agirman G, Yu KB, Hsiao EY. Signaling inflammation across the gut-brain axis. Science, 2021; 374(6571):1087-1092. https://doi.org/10.1126/science.abi6087
32. Li J, Cai H, Zhang Y, et al. Dysbiosis of gut microbiota is associated with pathogenesis of peptic ulcer diseases through inflammatory proteins: A Mendelian randomization study. Medicine (Baltimore), 2024; 103(39):e39814. https://doi.org/10.1097/MD.0000000000039814
33. Monteiro RC, Rafeh D, Gleeson PJ. Is there a role for gut microbiome dysbiosis in IgA nephropathy? Microorganisms, 2022; 10(4):683. https://doi.org/10.3390/microorganisms10040683
34. Backert S, Clyne M, Tegtmeyer N. Molecular mechanisms of gastric epithelial cell adhesion and injection of CagA by Helicobacter pylori. Cell Communication and Signaling, 2011; 9:28. https://doi.org/10.1186/1478-811X-9-28
35. Wroblewski LE, Peek RM. Targeted disruption of the epithelial-barrier by Helicobacter pylori. Cell Communication and Signaling, 2011; 9:29. https://doi.org/10.1186/1478-811X-9-29
36. Alzahrani S, Lina TT, Gonzalez J, Pinchuk IV, Beswick EJ, Reyes VE. Effect of Helicobacter pylori on gastric epithelial cells. World Journal of Gastroenterology, 2014; 20(36):12767. https://doi.org/10.3748/wjg.v20.i36.12767
37. Suzuki H, Moayyedi P. Helicobacter pylori infection in functional dyspepsia. Nature Reviews Gastroenterology & Hepatology, 2013; 10(3):168-174. https://doi.org/10.1038/nrgastro.2013.9
38. Warren JR, Marshall B. Unidentified curved bacilli on gastric epithelium in active chronic gastritis. The Lancet, 1983; 321(8336):1273-1275. https://doi.org/10.1016/S0140-6736(83)92719-8
39. Wroblewski LE, Peek RM, Wilson KT. Helicobacter pylori and gastric cancer: Factors that modulate disease risk. Clinical Microbiology Reviews, 2010; 23(4):713-739. https://doi.org/10.1128/CMR.00011-10
40. Ali A, AlHussaini KI. Helicobacter pylori: A contemporary perspective on pathogenesis, diagnosis and treatment strategies. Microorganisms, 2024; 12(1):222. https://doi.org/10.3390/microorganisms12010222
41. Kim MS, Kim Y, Choi H, et al. Transfer of a healthy microbiota reduces amyloid and tau pathology in an Alzheimer’s disease animal model. Gut, 2020; 69(2):283–294. https://doi.org/10.1136/gutjnl-2018-317431
42. Palm NW, de Zoete MR, Flavell RA. Immune-microbiota interactions in health and disease. Clinical Immunology, 2015; 159(2):122–127. https://doi.org/10.1016/j.clim.2015.05.014
43. Shin Y, Han S, Kwon J, et al. Roles of short-chain fatty acids in inflammatory bowel disease. Nutrients, 2023; 15(20):4466. https://doi.org/10.3390/nu15204466
44. Lynch SV, Pedersen O. The human intestinal microbiome in health and disease. The New England Journal of Medicine, 2016; 375(24):2369–2379. https://doi.org/10.1056/NEJMra1600266
45. Freedberg DE, Lebwohl B, Abrams JA. The impact of proton pump inhibitors on the human gastrointestinal microbiome. Clinics in Laboratory Medicine, 2014; 34(4):771. https://doi.org/10.1016/j.cll.2014.08.008
46. Nugent CC, Falkson SR, Terrell JM. H2 blockers. Journal of Clinical Gastroenterology, 2024; 5:143–148. https://doi.org/10.1097/00004836-198312001-00014
47. Zaman T, Haq A, Ahmad R, et al. The role of probiotics in the eradication of Helicobacter pylori and overall impact on management of peptic ulcer: A study involving patients undergoing triple therapy in Bangladesh. Cureus, 2024; 16(3):e56283. https://doi.org/10.7759/cureus.56283
48. Alkim H, Koksal AR, Boga S, Sen I, Alkim C. Role of bismuth in the eradication of Helicobacter pylori. American Journal of Therapeutics, 2017; 24(6):E751–E757. https://doi.org/10.1097/MJT.0000000000000389
49. Tai FWD, McAlindon ME. Non-steroidal anti-inflammatory drugs and the gastrointestinal tract. Clinical Medicine (Northfield Il), 2021; 21(2):131. https://doi.org/10.7861/clinmed.2021-0039
50. Ballinger A. Cytoprotection with misoprostol: Use in the treatment and prevention of ulcers. Digestive Diseases, 1994; 12(1):37–45. https://doi.org/10.1159/000171435
51. Zhang W, Lian Y, Li Q, et al. Preventative and therapeutic potential of flavonoids in peptic ulcers. Molecules. 2020;25(20):4626. https://doi.org/10.3390/molecules25204626
52. Kunnumakkara AB, Hegde M, Parama D, et al. Role of turmeric and curcumin in prevention and treatment of chronic diseases: Lessons learned from clinical trials. ACS Pharmacology & Translational Science. 2023;6(4):447–471. https://doi.org/10.1021/acptsci.2c00012
53. Mao QQ, Xu XY, Cao SY, et al. Bioactive compounds and bioactivities of ginger (Zingiber officinale Roscoe). Foods. 2019;8(6):185. https://doi.org/10.3390/foods8060185
54. Sharifi-Rad M, Roberts TH, Matthews KR, et al. Ethnobotany of the genus Taraxacum—phytochemicals and antimicrobial activity. Phytotherapy Research. 2018;32(11):2131–2145. https://doi.org/10.1002/ptr.6157
55. Sharifi-Rad M, Nazaruk J, Polito L, et al. Matricaria genus as a source of antimicrobial agents: From farm to pharmacy and food applications. Microbiological Research. 2018;215:76–88. https://doi.org/10.1016/j.micres.2018.06.010
56. de Jesus NZT, de Souza Falcão H, Gomes IF, et al. Tannins, peptic ulcers and related mechanisms. International Journal of Molecular Sciences. 2012;13(3):3203–3228. https://doi.org/10.3390/ijms13033203
57. Lukic J, Chen V, Strahinic I, et al. Probiotics or pro-healers? The role of beneficial bacteria in tissue repair. Wound Repair and Regeneration. 2018;25(6):912–922. https://doi.org/10.1111/wrr.12607
58. Rahnama M, Mehrabani D, Japoni S, Edjtehadi M, Saberi-Firoozi M. The healing effect of licorice (Glycyrrhiza glabra) on Helicobacter pylori-infected peptic ulcers. Journal of Research in Medical Sciences. 2013;18(6):532–535. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3818629/
59. Slippery elm. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. National Institute of Diabetes and Digestive and Kidney Diseases. Published January 5, 2024. https://www.ncbi.nlm.nih.gov/books/NBK599741/
60. Skoufou M, Tsigalou C, Vradelis S, Bezirtzoglou E. The networked interaction between probiotics and intestine in health and disease: A promising success story. Microorganisms. 2024;12(1):194. https://doi.org/10.3390/microorganisms12010194
61. Markowiak P, Ślizewska K. Effects of probiotics, prebiotics, and synbiotics on human health. Nutrients. 2017;9(9):1021. https://doi.org/10.3390/nu9091021
62. Blottière HM. The gut microbiota and obesity. In: Energy Balance and Obesity. 2017. Accessed March 24, 2025. https://www.ncbi.nlm.nih.gov/books/NBK565809/
63. Le Chatelier E, Nielsen T, Qin J, et al. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013;500(7464):541–546. https://doi.org/10.1038/nature12506
64. Crudele L, Gadaleta RM, Cariello M, Moschetta A. Gut microbiota in the pathogenesis and therapeutic approaches of diabetes. eBioMedicine. 2023;97:104821. https://doi.org/10.1016/j.ebiom.2023.104821
65. Boicean A, Birlutiu V, Ichim C, Anderco P, Birsan S. Fecal microbiota transplantation in inflammatory bowel disease. Biomedicines. 2023;11(4):1016. https://doi.org/10.3390/biomedicines11041016
66. Choi KW, Chen CY, Stein MB, et al. Assessment of bidirectional relationships between physical activity and depression among adults: A 2-sample Mendelian randomization study. JAMA Psychiatry. 2019;76(4):399–408. https://doi.org/10.1001/jamapsychiatry.2018.4175
Published



How to Cite
Issue
Section
Copyright (c) 2025 Deepannita Roy Mukherjee, Sayak Tanbir, Sohel Mondal, Soumik Tarafder, Dona Biswas, Soumyadeb Dutta, Saikat Santra, Pinki Biswas

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).