Abstract and Introduction
Abstract
Background: Functional dyspepsia (FD) is one of the most frequent conditions in gastroenterological outpatient health care. Most recent research in FD has shifted its focus to duodenal pathophysiological mechanisms, although current treatments still focus mainly the stomach.
Aim: The aim of the study was to provide a comprehensive overview of the pathophysiology of FD focusing on a paradigm shift from gastric towards duodenal mechanisms.
Methods: We conducted a literature search in PubMed for studies describing mechanisms that could possibly cause FD.
Results: The pathophysiology of FD remains incompletely understood. Recent studies show that duodenal factors such as acid, bile salt exposure and eosinophil and mast cell activation correlate with symptom pattern and burden and can be associated with gastric sensorimotor dysfunction. The evolving data identify the duodenum an interesting target for new therapeutic approaches. Furthermore, the current first-line treatment, that is proton pump inhibitors, reduces duodenal low-grade inflammation and FD symptoms.
Conclusion: Future research for the treatment of FD should focus on the inhibition of duodenal mast cell activation, eosinophilia and loss of mucosal integrity.
Introduction
Functional dyspepsia (FD), defined as symptoms affecting daily life which are thought to originate from the gastroduodenal region, such as postprandial fulness, early satiation, epigastric pain and burning without underlying organic disease likely to explain the symptoms, is a highly prevalent condition.[1] Based on the Rome Global Epidemiology Study, FD is estimated to affect approximately 7% of the adult population, causing major interference with daily activities and thus with quality of life, and generating major health economic expenses.[2] FD can be divided into two subgroups based on symptom patterns. The postprandial distress syndrome (PDS) is defined by the presence of bothersome early satiation and/or postprandial fullness at least three times a week while the epigastric pain syndrome (EPS) is characterised by bothersome epigastric pain and/or burning at least once a week. The diagnosis of FD requires the absence of organic, systemic, or metabolic disease upon routine investigation, including endoscopy, and these criteria must be fulfilled during 3 months with symptom onset at least 6 months before diagnosis.[3]
The majority of patients (67%) have PDS and 15% have EPS, and both are present in an 18% overlap group.[2] As different pathogenic mechanisms may be underlying the symptoms in EPS, this review will focus on PDS, the largest FD subgroup.[4] Patients with PDS symptoms and postprandial epigastric pain or other postprandial symptoms, are considered part of postprandial distress syndrome in the Rome IV classification, which has decreased the overlap group in comparison with the Rome III consensus.[5]
Currently recommended treatments for FD/PDS are Helicobacter pylori eradication (if applicable), proton pump inhibitors (PPI), prokinetics or neuromodulators.[6] These therapies are mainly symptomatic as the pathophysiological mechanisms underlying FD are poorly understood. A role for dietary factors in FD is evident from the symptom-triggering effect of a meal in the vast majority of patients.[7] Göktaş et al used the food frequency questionnaire to identify symptom-triggering foods in 168 FD patients.[8] They identified fatty and spicy food as well as carbonated drinks as possible symptom aggravating factors. Nevertheless, to date there is no proven efficacious dietary treatment approach to FD/PDS.
In this review, we will discuss the putative pathogenic mechanisms underlying symptom generation in FD as they are conceptualised today, with a focus on recent research. While initial focus of pathophysiological studies was gastric sensorimotor dysfunction, the attention has now shifted to the duodenal mucosa, in interaction with luminal factors such as acid, microbiota, bile and food.
Aliment Pharmacol Ther. 2023;57(8):851-860. © 2023 Blackwell Publishing
