The Role of Immune Mechanisms and Gastroduodenal Microbiota Alterations in the Pathogenesis of Gastric and Duodenal Peptic Ulcer Disease

Introduction. Peptic ulcer disease remains a significant clinical problem despite the declining prevalence of Helicobacter pylori-associated forms and the expanding possibilities of eradication therapy. Current evidence indicates that the development of ulcerative lesions is determined not only by acid-peptic aggression but also by the complex interaction among Helicobacter pylori (H. pylori), the gastric microbiota, and the host immune system. The aim of this review is to summarize and analyze current evidence on the immunological and microbiological aspects of peptic ulcer disease, to identify the key mechanisms underlying the interaction between H. pylori, the gastric microbiota, and the host immune response, and to outline the diagnostic and therapeutic prospects arising from these mechanisms. Materials and methods. An analytical review of publications addressing the immunological and microbiological aspects of peptic ulcer disease was conducted. The analysis included clinical guidelines, systematic reviews, meta-analyses, and original research articles published primarily between 2017 and 2025 and indexed in the PubMed/Medline, Scopus, Web of Science, eLibrary, and Google Scholar databases. The sources were selected based on their relevance to the topic, methodological transparency, and the currency of the data. Results. The literature analysis demonstrated that the key mechanism underlying the chronicity of inflammation in peptic ulcer disease is the activation of both innate and adaptive immunity in the setting of persistent Helicobacter pylori infection. Signaling pathways involved in innate immune recognition, the predominance of a T-helper–mediated inflammatory response, deficiencies in regulatory mechanisms, and bacterial immune evasion strategies all play significant roles. According to the studies included in this review, H. pylori infection and prolonged acid suppression contribute to dysbiotic alterations in the gastric microbiota, reduced microbial diversity, and the “oralization” of the gastric environment. These changes are associated with the persistence of inflammation, impaired mucosal repair, variability in treatment response, and an increased risk of disease recurrence. Endoscopic confirmation of the ulcer, verification of H. pylori infection, and assessment of eradication remain the cornerstone diagnostic approaches, while immune- and microbiome-based biomarkers are considered promising directions for future diagnostic development. Discussion and conclusion. The contemporary understanding of peptic ulcer disease requires the integration of infectious, immunological, and microbiome-based concepts. The most promising approaches appear to be personalized treatment strategies that combine etiological therapy, protection of the gastric mucosa, and correction of microbiota disturbances.