Changes in gastrointestinal tract function and structure in functional dyspepsia

Functional dyspepsia is an extremely common disorder of gastrointestinal function. The disorder is thought to be heterogeneous, with different pathophysiological mechanisms underlying varied symptom patterns. A diversity of changes in gastrointestinal tract function and structure has been described in functional dyspepsia. These involve alterations in the stomach, such as impaired accommodation, delayed gastric emptying and hypersensitivity, and alterations in the duodenum, such as increased sensitivity to duodenal acid and/or lipids and low-grade inflammation. In this Review, we summarize all these abnormalities in an attempt to provide an integrated overview of the pathophysiological mechanisms in functional dyspepsia.status: publishe

Therapeutic options for functional dyspepsia

Functional dyspepsia (FD) is defined by the presence of chronic gastroduodenal symptoms in the absence of organic or systemic disease that explains them, and a negative upper endoscopy. According to the Rome III consensus, FD can be subdivided into PDS (postprandial distress syndrome) and EPS (epigastric pain syndrome). In patients with mild symptoms, reassurance and lifestyle adjustments are often sufficient. Pharmacotherapy, for those with more severe or persisting symptoms, includes the use of proton pump inhibitors (PPIs), prokinetics and psychotropic agents. In those diagnosed with Helicobacter pylori infection, eradication is recommended, although the symptom impact is often limited. PPIs are the initial therapy of choice for EPS, while prokinetics can be used in PDS. Tricyclic antidepressants can be used for refractory symptoms, especially in EPS. Emerging therapies include the novel gastroprokinetic agent acotiamide for PDS, fundus-relaxing 5-HT1A agonists in patients with PDS/early satiation and mirtazapine for FD with weight loss. © 2014 S. Karger AG, Basel.status: publishe

Authors' response: impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia

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Postprandial symptoms originating from the stomach in functional dyspepsia

Functional dyspepsia (FD) is characterized by chronic epigastric symptoms. The stomach has been held responsible for the generation of symptoms, but the latest reports have pointed out that also the duodenum can be implicated in the pathophysiology. The aim of this study was to elucidate which dyspeptic symptoms originate from the stomach and/or from the small intestine after a meal.status: publishe

Altered duodenal bile salt concentration and receptor expression in functional dyspepsia

Background: Functional dyspepsia is a common functional gastrointestinal disorder in which a variety of pathophysiological mechanisms such as increased intestinal permeability and low-grade inflammation are involved. The factor causing these alterations, however, has not been identified. Objective: We aimed to evaluate the luminal bile salt content and receptor expression in patients with functional dyspepsia and healthy volunteers. Methods: Gastroduodenoscopy was performed to obtain duodenal biopsies from 25 healthy volunteers and 25 patients with functional dyspepsia (Rome III) to measure duodenal bile salt receptor expression with Western blot. Duodenal fluid aspirates were collected at fixed time points during fasted and fed state conditions and bile salt composition analysis was performed by liquid chromatography-mass spectrometry/mass spectrometry. Results: Patients (N = 17) displayed decreased fasted bile salt concentrations compared to healthy volunteers (N = 20) over time (1.8 ± 0.3 mM vs 3.6 ± 0.5 mM; p = 0.03). In addition, an increased expression of duodenal bile salt sensor vitamin D receptor was found in patients (3.7 ± 1.0-fold; p < 0.0005; N = 24 for both groups). Conclusion: Patients with functional dyspepsia are characterized by a decreased duodenal bile salt concentration in fasted state and an increased duodenal vitamin D receptor expression.status: publishe

Activation of Eosinophils and Mast Cells in Functional Dyspepsia: an Ultrastructural Evaluation

We recently identified mucosal mast cell and eosinophil hyperplasia in association with a duodenal impaired barrier function in functional dyspepsia (FD). We aimed to further describe the implication of these immune cells by assessing their activation state at the ultrastructural level and by evaluating the association between impaired epithelial integrity and immune activation. Duodenal biopsies were obtained from 24 FD patients and 37 healthy controls. The ultrastructure of mast cells and eosinophils was analyzed by transmission electron microscopy. Transepithelial electrical resistance and paracellular permeability were measured to evaluate epithelial barrier function. The type of degranulation in eosinophils and mast cells was piecemeal. Eosinophils displayed higher degree of degranulation in FD patients than in controls (p < 0.0001). Quantification revealed a decreased granular density in eosinophils of FD patients (p < 0.0001). The degree of degranulation in mast cells was similar in both groups. However, a more heterogeneous profile was found in the FD group (p < 0.0001). No association between epithelial integrity and the number and activation state of mucosal eosinophils and mast cells was found. We demonstrated ultrastructural changes in degranulation state of eosinophils and mast cells, suggesting that eosinophil and mast cell activation play a role in the pathophysiology of FD.status: publishe

Pathophysiological Abnormalities in Functional Dyspepsia Subgroups According to the Rome III Criteria

The Rome III criteria proposed to subdivide functional dyspepsia (FD) into a postprandial distress syndrome (PDS) group, characterized by the presence of postprandial fullness and/or early satiety, and an epigastric pain syndrome (EPS) group, characterized by the presence of epigastric pain and/or epigastric burning. It has been suggested that different pathophysiological mechanisms underlie the symptom presentations in these subgroups that might determine treatment choices. The aim of this study was to investigate the prevalence of gastric sensorimotor dysfunction in the PDS, EPS, and overlap groups and to evaluate potential differential associations with dyspeptic symptom scores.status: publishe