Acid-Lowering Agents in Functional Dyspepsia: Assessing the Role and Effectiveness of Proton Pump Inhibitors and Beyond
- 1Department of Gastroenterology and Hepatology, The First Affiliated Hospital, Sun Yat-sen University Guangzhou China
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.
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BibTeX
@article{ma2026acidlowering,
title = {{Acid-Lowering Agents in Functional Dyspepsia: Assessing the Role and Effectiveness of Proton Pump Inhibitors and Beyond}},
author = {Ruiqi Ma and Yinglian Xiao},
journal = {Journal of Neurogastroenterology and Motility},
year = {2026},
month = oct,
doi = {10.5056/jnm25237},
url = {https://doi.org/10.5056/jnm25237},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Acid-Lowering Agents in Functional Dyspepsia: Assessing the Role and Effectiveness of Proton Pump Inhibitors and Beyond
AU - Ruiqi Ma
AU - Yinglian Xiao
PY - 2026
DA - 2026/10/31
JO - Journal of Neurogastroenterology and Motility
DO - 10.5056/jnm25237
UR - https://doi.org/10.5056/jnm25237
AB - 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.
SN - 2093-0879
SN - 2093-0887
ER -