S3145 Immune Dysfunction and Inflammatory Pathways in Functional Dyspepsia: A Systematic Review

Introduction: Functional dyspepsia (FD) is a disorder of the gastrointestinal (GI) tract in which persistent upper abdominal pain exists without any visible cause. New research reveals that small immune system issues or mild upper GI tract inflammation could cause FD symptoms. In FD, the duodenum often has more eosinophils and mast cells. This suggests that FD's “micro-inflammation” affects the duodenum. Methods: We systematically checked for signs of immune system and inflammatory activity in people with FD. From 2000 to 2025, PubMed, Embase, Google Scholar, Cochrane Library, and Web of Science were explored for studies that examined mucosal immune cells (eosinophils, mast cells, lymphocytes) or cytokines found in FD compared to control groups. The histopathology data from gastric/duodenal biopsies and the counts of immune cells were extracted from the database, together with some translational results. The quality of the studies was considered moderate. A qualitative synthesis approach was taken because the endpoints were not all similar. Results: We included 23 studies based on PRISMA criteria. Small immunological changes were noted in FD, with case-control studies showing increased duodenal eosinophils and, to a lesser extent, mast cells in FD patients versus controls. Both postprandial distress and epigastric pain subtypes were linked to higher duodenal eosinophil counts. A modest increase in eosinophils and mast cells was also seen in the gastric antrum. Though subtle on histology, these findings reflect enhanced immune activity. Some studies also reported impaired duodenal barrier function and elevated cytokine expression, with variable clinical impact. Increased α4β7⁺ T cells suggest mucosal immune imbalance. Despite variability, the consistent finding was elevated mucosal eosinophils and mast cells in FD, supporting an immune-mediated mechanism. Conclusion: Evidence indicates that low-grade inflammation and immune dysregulation, including duodenal eosinophilia and mast cell infiltration, may contribute to symptoms like early satiety, bloating, and pain in FD. Access to larger, well-characterized patient cohorts is needed to clarify these mechanisms. These insights support developing immune-targeted therapies, such as agents that modulate eosinophils and mast cells. Once considered non-organic, FD may have an immune basis, opening doors to more effective treatments.