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Drug-resistant strains of Helicobacter pylori and poor treatment response are the main reasons for the failure in eradicating it in patients. Polyunsaturated fatty acids (PUFA) have an inhibitory effect on bacterial growth. The aim of this study was to investigate the effect of PUFA in combination with standard triple therapy on apoptosis in H. pylori infected subjects with dyspeptic symptoms. This study was a double-blind clinical trial in which 34 H. pylori infected subjects with dyspeptic symptoms were randomly divided into two groups of 17 patients. The control group received standard triple therapy (amoxicillin, clarithromycin and omeprazole) and the experimental group received the standard therapy and PUFA for two weeks. Gene expression levels of caspase-3, BCL-2 and Bad proteins were studied with real-time PCR, while protein levels were quantified in frozen sections and using immunohistochemistry. Compared with the control group, a significant increase ( p  < 0.01) was observed in the expression of caspase-3 and Bad genes and a significant reduction ( p  < 0.05) in the expression of Bcl-2 gene. The protein level of active caspase-3 and Bad protein was significantly increased and the level of Bcl-2 protein was significantly decreased ( p  < 0.05). The results of this study show that oral administration of PUFA in combination with the standard triple therapy increased apoptosis in H. pylori -infected patients with dyspeptic symptoms. This increase in apoptosis may partly reduce drug resistance in these patients. Our results suggest inclusion of a dietary PUFA containing fatty acid supplement may improve treatment of patients that are refractory to the standard triple therapy.

Background In Traditional Chinese Medicine (TCM) theory, functional dyspepsia (FD) can be divided into different syndromes according to different clinical symptoms and signs, and the most common one is spleen-deficiency and qi-stagnation syndrome that can be treated by Chinese traditional patent medicine --- two kinds of Zhizhu pills, between which the primary difference in ingredients is that one contains immature orange fruit of Citrus aurantium L.(IFCA) and the other contains that of Citrus sinensis Osbeck (IFCS). The trial's objective was to compare the efficacy of two kinds of Zhizhu pills on symptom changes in patients with FD of spleen-deficiency and qi-stagnation syndrome. Methods A randomized, group sequential, double-blinded, multicenter trial was conducted in patients with FD of spleen-deficiency and qi-stagnation syndrome at 3 hospitals in Beijing between June 2003 and May 2005. Participants were randomly allocated into two groups (IFCA group and IFCS group) in a 1:1 ratio, and respectively took one of the two kinds of Zhizhu pills orally, 6 g each time, 3 times a day, for 4 weeks. Statistical analysis was performed with use of a group sequential method, the triangular test (TT). Results A total of 163 patients were randomized, and 3 patients were excluded from analysis because of early dropouts, leaving 160 patients (IFCA group: n = 82; IFCS group: n = 78) for statistical analysis. Three interim analyses were done after 62, 116, and 160 patients had completed their 4-week treatment, respectively. At the third interim analysis, the sample path crossed the upper boundary and the trial was stopped, the cure-markedly effective rates were 45% for IFCS group and 67% for IFCA group, respectively, the one-sided p -value was 0.0036, the median unbiased estimate of the odds ratio (OR) for the benefit of IFCA relative to IFCS was 2.91 with 95%CI: 1.40 to 6.06. No adverse events were observed in the two groups. Conclusions Zhizhu pills containing IFCA was superior to Zhizhu pills containing IFCS in the treatment of FD of spleen-deficiency and qi-stagnation syndrome. The application of group sequential analysis in clinical trials of TCM may offer some financial and ethical benefits. Trial Registration Chinese Clinical Trial Registry (ChiCTR): ChiCTR-TRC-00000485

Objective Functional dyspepsia (FD) is an extremely common functional gastrointestinal disorder, the pathophysiology of which is poorly understood. We hypothesised that impaired intestinal barrier function is involved in the onset and persistence of this disorder by inducing low-grade inflammation. Therefore, our aim was to evaluate duodenal mucosal integrity and low-grade inflammation in patients with FD. Design Duodenal biopsy specimens were obtained from 15 patients with FD fulfilling the Rome III criteria and 15 age- and gender-matched healthy volunteers. Transepithelial electrical resistance (TEER) and paracellular permeability were measured in Ussing chambers. Expression of cell-to-cell adhesion proteins was evaluated by real-time PCR, western blot and/or immunofluorescence. Numbers of mast cells, eosinophils and intraepithelial lymphocytes were assessed by immunohistochemistry. Results Patients with FD displayed lower TEER and increased paracellular passage compared with healthy controls, which is indicative of impaired mucosal integrity. In addition, abnormal expression of cell-to-cell adhesion proteins at the level of tight junctions, adherens junctions and desmosomes was shown. Furthermore, patients were characterised by the presence of low-grade inflammation, as demonstrated by increased infiltration of mucosal mast cells and eosinophils. A significant association between the expression level of several cell-to-cell adhesion proteins, the extent of increased permeability and the severity of low-grade inflammation was found. Conclusions These findings challenge the classical paradigm that patients with FD show no structural changes in the gastrointestinal tract. We suggest that impaired intestinal barrier function is a pathophysiological mechanism in FD. Thus, restoration of intestinal barrier integrity may be a potential therapeutic target for treating patients with FD.

An intact and well-functioning enteric nervous system is necessary to efficiently organize gut function. Functional gastrointestinal disorders are pathological entities in which gut function is impaired without a clearly established pathophysiology. On the basis of the relative ease with which intestinal biopsies can be obtained, and taking advantage of a recently developed optical recording technique, we evaluated whether functional neuronal defects exist in enteric nerves of patients with functional dyspepsia (FD). The submucous plexus isolated from duodenal biopsies taken from FD patients and control subjects was used to functionally and morphologically examine nerves and ganglionic architecture (neurons and glial cells). In light of previous studies reporting eosinophil and mast cell infiltration in the gut mucosa of FD patients, we also examined whether these cells infiltrated the submucous plexus and whether this correlated with neuronal activity and specific clinical symptoms. We demonstrate that neuronal functioning is impaired in the submucous plexus of FD patients, as shown by decreased calcium responses to depolarization and electrical stimulation. Glial (S100) and neuronal (HuCD) markers show signs of gliosis, altered ganglionic architecture, and neuronal abnormalities in the submucous plexus of FD patients. We found that eosinophils and mast cells infiltrated the submucous layer of FD patients to a much larger extent than in controls. A significant correlation was found between the number of these cells and the calcium transient amplitudes measured in submucous ganglia. We provide the first direct evidence that FD is characterized by functional and structural abnormalities within the submucous ganglion plexus, which may be of future predictive and diagnostic value in the treatment of FD patients.

Duodenal epithelial barrier impairment and immune activation may play a role in the pathogenesis of functional dyspepsia (FD). This study was aimed to evaluate the duodenal epithelium of patients with FD and healthy individuals for detectable microscopic structural abnormalities. This is a prospective study using esophagogastroduodenoscopy enhanced with duodenal confocal laser endomicroscopy (CLE) and mucosal biopsies in patients with FD (n = 16) and healthy controls (n = 18). Blinded CLE images analysis evaluated the density of epithelial gaps (cell extrusion zones), a validated endoscopic measure of the intestinal barrier status. Analyses of the biopsied duodenal mucosa included standard histology, quantification of mucosal immune cells/cytokines, and immunohistochemistry for inflammatory epithelial cell death called pyroptosis. Transepithelial electrical resistance (TEER) was measured using Ussing chambers. Epithelial cell-to-cell adhesion proteins expression was assessed by real-time polymerase chain reaction. Patients with FD had significantly higher epithelial gap density on CLE in the distal duodenum than that of controls (P = 0.002). These mucosal abnormalities corresponded to significant changes in the duodenal biopsy samples of patients with FD, compared with controls, including impaired mucosal integrity by TEER (P = 0.009) and increased number of epithelial cells undergoing pyroptosis (P = 0.04). Reduced TEER inversely correlated with the severity of certain dyspeptic symptoms. Furthermore, patients with FD demonstrated altered duodenal expression of claudin-1 and interleukin-6. No differences in standard histology were found between the groups. This is the first report of duodenal CLE abnormalities in patients with FD, corroborated by biopsy findings of epithelial barrier impairment and increased cell death, implicating that duodenal barrier disruption is a pathogenesis factor in FD and introducing CLE a potential diagnostic biomarker in FD.

Background and aims: Dietary fat plays a role in the pathophysiology of symptoms in functional dyspepsia (FD). In healthy subjects, cognitive factors enhance postprandial fullness; in FD patients, attention increases gut perception. We hypothesised that the information given to patients about the fat content of a meal would affect dyspeptic symptoms. Methods: Fifteen FD patients were each studied on four occasions in a randomised double blind fashion. Over two days they ingested a high fat yoghurt (HF) and over the other two days a low fat yoghurt (LF). For each yoghurt, the patients received the correct information about its fat content on one day (HF-C, LF-C) and the opposite (wrong) information on the other day (HF-W, LF-W). Dyspeptic symptoms, plasma cholecystokinin (CCK) concentrations, and gastric volumes were evaluated. Results: Both the fat content and information about the fat content affected fullness and bloating scores—both were higher after HF-C compared with LF-C, and LF-W compared with LF-C, with no differences between HF-C and HF-W. Nausea scores were higher after HF compared with LF, with no effect of the information about fat content. No differences between discomfort and pain scores were found between study conditions. Plasma CCK and gastric volumes were greater following HF compared with LF, with no effect of the information given to the patients. All differences are p<0.05. Conclusions: Cognitive factors contribute to symptom induction in FD. Low fat foods may also elicit symptoms if patients perceive foods as high in fat, while CCK and gastric volumes do not appear to be affected by cognitive factors.

When the protective mechanisms of the gastroesophageal mucosa are overwhelmed by injurious factors, the structural and functional mucosal integrity is compromised, resulting in a wide spectrum of disorders. Poliprotect has recently been shown to be non-inferior to standard-dose omeprazole for the treatment of endoscopy-negative patients with heartburn and/or epigastric pain or burning. Here, we provide preclinical data describing the mechanism of action of the Poliprotect formulation, a 100% natural, biodegradable, and environmental friendly medical device according to EU 2017/745 and containing UVCB (unknown or variable composition, complex-reaction products, or biological materials) substances of botanical and mineral origin, according to the REACH and European Chemical Agency definitions. Different in vitro assays demonstrated the capability of Poliprotect to adhere to mucus-secreting gastric cells and concomitantly deliver a local barrier with buffering and antioxidant activity. In studies conducted in accordance with systems biology principles, we evaluated the effects of this barrier on human gastric cells exposed to acidic stress. Biological functions identified via Ingenuity Pathway Analysis highlighted the product’s ability to create a microenvironment that supports the mucosal structural and functional integrity, promotes healing, and restores a balanced mucosal inflammatory status. Additionally, transepithelial electrical resistance and an Ussing chamber showed the product’s capability of preserving the integrity of the gastric and esophageal epithelial barriers when exposed to an acid solution. Two in vivo models of erosive gastropathy further highlighted its topical protection against ethanol- and drug-induced mucosal injury. Overall, our findings sustain the feasibility of a paradigm shift in therapeutics R&D by depicting a very innovative and desirable mode of interaction with the human body based on the emerging biophysical, rather than the pharmacological properties of these therapeutic agents.

Functional dyspepsia is characterised by chronic symptoms of post-prandial distress or epigastric pain not associated with defined structural pathology. Increased peripheral gut-homing T cells have been previously identified in patients. To date, it is unknown if these T cells were antigen-experienced, or if a specific phenotype was associated with FD. This study aimed to characterise T cell populations in the blood and duodenal mucosa of FD patients that may be implicated in disease pathophysiology. We identified duodenal T cell populations from 23 controls and 49 Rome III FD patients by flow cytometry using a surface marker antibody panel. We also analysed T cell populations in peripheral blood from 37 controls and 61 patients. Where available, we examined the number of duodenal eosinophils in patients and controls. There was a shift in the duodenal T helper cell balance in FD patients compared to controls. For example, patients had increased duodenal mucosal Th2 populations in the effector (13.03 ± 16.11, 19.84 ± 15.51, =0.038), central memory (23.75 ± 18.97, 37.52 ± 17.51, =0.007) and effector memory (9.80±10.50 vs 20.53±14.15, =0.001) populations. Th17 populations were also increased in the effector (31.74±24.73 vs 45.57±23.75, =0.03) and effector memory (11.95±8.42 vs 18.44±15.63, =0.027) subsets. Peripheral T cell populations were unchanged between FD and control. Our findings identify an association between lymphocyte populations and FD, specifically a Th2 and Th17 signature in the duodenal mucosa. The presence of effector and memory cells suggest that the microinflammation in FD is antigen driven.

Functional dyspepsia (FD) is a functional gastrointestinal disorder diagnosed by symptom-based criteria. It has been said that duodenal immune activation plays a role in the pathogenesis of FD. The primary aims of the study were to compare the total number of duodenal eosinophil and evaluate the eosinophil degranulation rate, number of duodenal degranulated eosinophil and mast cell between patients with FD and healthy subjects. We enrolled 96 patients with FD and 24 healthy controls at Sir Run Run Shaw Hospital. The total number of eosinophil was comparable in the second portion of duodenum (D2) and duodenal bulb (D1) between patients with FD and healthy controls (all P  > 0.05). Significant higher eosinophil degranulation positive rate in D2 ( P  = 0.003) and a trend towards higher in D1 ( P  = 0.084) were observed in patients with FD compared with healthy controls. Moreover, the number of duodenal degranulated eosinophil in patients with FD were significantly increased than healthy controls in D1(9.8 ± 6.3 vs 2.9 ± 2.1 per HPF, P  = 0.0002) and a trend towards increase in D2 (10.7 ± 7.7 vs 5.3 ± 0.9 per HPF, P  = 0.077), respectively. However, degranulated mast cells in patients with FD were almost same with healthy controls. Increased eosinophils degranulation in duodenum play an important role in pathogenesis of FD.

Correspondence to Dr Shahab Abid, Medicine, Aga Khan University, Karachi 3500, Pakistan; shahab.abid@aku.edu A 33-year-old male patient presented to our gastroenterology clinic, in January 2020, with complains of early satiety, regurgitation, heartburn and weakness for the past several months. Underlying conditions that lead to prolonged injury of the gastric mucosa such as peptic ulcer disease, tuberculosis and pernicious anaemia have been found to be the risk factors in the development of squamous metaplasia.2 Since most patients with autoimmune atrophic gastritis do not develop gastric squamous metaplasia, it is possible that our patient developed it because of the dual hit with duodenogastric reflux, following pyloroplasty. [...]a long-term follow-up with frequent monitoring of symptoms is required.3 Ethics statements Patient consent for publication Obtained.