Work

Acid-Lowering Agents in Functional Dyspepsia: Assessing the Role and Effectiveness of Proton Pump Inhibitors and Beyond

Year: 2026

Type: review

Abstract: Functional dyspepsia (FD) is a prevalent functional gastrointestinal disorder with complex pathophysiology. While acid exposure is implicated in its pathogenesis, the therapeutic focus is shifting toward understanding the full scope of acid-suppressive therapy. This review aims to assess the role and effectiveness of proton pump inhibitors (PPIs) in FD, with particular emphasis on their mechanisms beyond acid suppression, and to explore the potential of novel acid-lowering agents. We synthesized current evidence from key clinical trials, meta-analyses, and mechanistic studies to evaluate the efficacy of PPIs and to elucidate their non-acid-suppressive effects. Meta-analyses confirm that PPIs are superior to placebo for global symptom relief in FD, with the most consistent benefits observed for epigastric pain and burning. Beyond their well-established acid-suppressive action, PPIs demonstrate significant non-acid-related effects that may contribute to their therapeutic action. These include anti-inflammatory properties, such as reducing duodenal eosinophil and mast cell infiltration, and modulation of gut microbiota and intestinal permeability. However, these mechanisms may also underlie potential long-term adverse effects. Potassium-competitive acid blockers (P-CABs) represent a promising new class of agents with pharmacological advantages, showing efficacy in initial studies, though their superiority over PPIs requires further validation. PPIs remain an evidence-based first-line therapy for FD, supported by proven efficacy and newly discovered pleiotropic mechanisms. However, their application should be individualized, with consideration of symptom subtype and potential long-term consequences. Future management strategies should focus on refined patient selection and the integration of novel agents like P-CABs.

Source: Journal of Neurogastroenterology and Motility

DOI: 10.5056/jnm25237

Authors: Ruiqi Ma, Yinglian Xiao

Institutions: Sun Yat-sen University, The First Affiliated Hospital, Sun Yat-sen University

Language: English

Topic: Gastrointestinal motility and disorders

Subfield: Gastroenterology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: diamond

Funder: National Natural Science Foundation of China