Diagnosing pediatric patients with chronic gastroduodenal symptoms is clinically challenging, with the role of gastric emptying testing being controversial. Body Surface Gastric Mapping (BSGM) is a new diagnostic test that can identify specific patient phenotypes in adults with gastric dysfunction. This study evaluates whether BSGM can delineate specific phenotypes in adolescents and provide clinically meaningful distinctions between gastroparesis and functional dyspepsia diagnoses.

A prospective cross-sectional study recruited adolescents aged 12 to 21 between 2022 and 2024. Controls were recruited from New Zealand and patients from the Children's Hospital of Philadelphia, USA. BSGM followed a standardized protocol, including simultaneous symptom reporting and completion of validated symptom, psychometric, and physical health questionnaires.

Fifty-six subjects were recruited (31 controls, 25 patients); median age 16; 96% of patients were female. Control data showed that adult reference intervals provided an acceptable interpretation framework. Patients with FD (n = 10) and gastroparesis (n = 15) had common symptoms, mental health, quality of life, and functional disability (all p > 0.05). Three distinct BSGM phenotypes were identified: BSGM Normal (n = 10), BSGM Delay (n = 8), and Low Stability/Low Amplitude (n = 7), having spectral differences in BMI-Adjusted Amplitude 34.6 versus 39.1 versus 19.9 (p = 0.01) and Gastric Alimetry Rhythm Index: 0.45 versus 0.45 versus 0.19 (p = 0.003). BSGM phenotypes demonstrated differences in symptoms (nausea p = 0.04), physical health (p = 0.04), and psychometrics (anxiety p = 0.03).

Adolescents with FD and gastroparesis have overlapping clinical profiles, making treatment challenging. Conversely, employing BSGM to categorize patients into distinct phenotypes reveals clinically relevant differences, offering avenues for individualized therapeutic pathways.

This study innovatively employs transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive physical therapy, to intervene in elderly patients with chronic insomnia (CI) comorbid with functional dyspepsia (FD). Through systematic investigation of the molecular mechanisms underlying vagus nerve pathway regulation in ameliorating intestinal inflammatory microenvironment and modulating central neurotransmitter homeostasis, this research aims to provide a novel, neuromodulation-based precision therapeutic approach characterized by favorable safety and tolerability for integrated management of geriatric comorbidities.

This double-blind randomized controlled trial will enroll 60 elderly patients (60-85 years) meeting ICSD-3 criteria for CI and Rome IV criteria for FD. Using block randomization with computer-generated sequences, eligible participants will be allocated 1:1 to either active taVNS group (n = 30) or sham control group (n = 30). The CFDA-certified transcutaneous vagus nerve stimulator (Model tVNS501, Reach Medical, China; Registration No. SuXieZhun20212090050) will be positioned at standardized anatomical sites: the concha cymba (the inferior margin of the intersection between the superior and inferior crura of the antihelix within the cymba conchae), electrical stimulation will deliver with fixed parameters (frequency: 80 Hz, pulse width: 100 μs, pulse 40-60s). The active group will receive validated taVNS parameters, while the sham group will undergo identical procedures without electrical output. Interventions will be administered 30 min per session, 5 sessions weekly for 3 consecutive weeks. Primary endpoints include changes in Pittsburgh Sleep Quality Index (PSQI) and Nepean Dyspepsia Symptom Index (NDSI) at week 3. Secondary outcomes encompass Insomnia Severity Index (ISI), 36-Item Short Form Survey (SF-36), and serum biomarkers (pro-inflammatory cytokines IL-1β, IL-4, IL-6, TNF-α, hs-CRP, TGF-β; neurotransmitters Dopamine (DA), serotonin (5-hydroxytryptamine, 5-HT), norepinephrine (NE), Glutamate (Glu), γ-aminobutyric acid (GABA)). Safety profiles will be systematically evaluated using CTCAE v5.0 criteria, with all adverse events documented throughout the study.

This study mitigate the adverse effects associated with the significant side effects of oral medications in elderly patients with CI comorbid with FD. It seeks to scientifically validate the clinical efficacy of taVNS therapy, elucidate its underlying anti-inflammatory and neuromodulatory mechanisms, and establish a multimodal evidence chain integrating "efficacy-inflammation-neuromodulation." By doing so, this research provides a novel, convenient, scientifically validated, effective, and safe non-pharmacological therapeutic approach for elderly patients with CI and FD, it offers innovative insights and methodologies for the development of pharmaceuticals, medical devices, and related products.

Functional dyspepsia (FD) is a prevalent health issue currently lacking optimal treatment options, with its global incidence rate increasing in recent years. Clinical studies have recently focused on the application of auriculotherapy in functional gastrointestinal disorders that are accompanied by negative emotions. However, few randomized controlled trials have investigated the use of auriculotherapy for FD patients with insomnia, leaving the therapeutic efficacy and safety largely undefined. This study aims to evaluate the clinical efficacy and safety of auriculotherapy in treating FD patients with insomnia.

This study is a single-center, randomized controlled clinical trial involving 80 patients with FD and insomnia. Using a central randomization system, the subjects are randomly assigned to the auricular acupressure group or the sham auricular acupressure group at a 1:1 ratio, with the auricular acupressure group targeting the concha region and the sham auricular acupressure group targeting the earlobe region. The primary outcome is the response rate at 2 weeks, and the secondary outcomes include the response rate at 8 weeks, sleep data assessed by actigraphy, modified Functional Dyspepsia Symptom Diary, short form-Nepean Dyspepsia Index, Self-rated Anxiety Scale, Self-rated Depression Scale, High Arousal Scale, and Heart Rate Variability. Efficacy results will be evaluated at baseline and at 2 and 8 weeks after treatment. Adverse events will be monitored throughout the study observation period.

The results of this trial are anticipated to validate the efficacy and safety of auriculotherapy in improving symptoms of FD and insomnia, as well as in reducing negative emotional states.

ClinicalTrials.gov, NCT06466044. Registered 14th May 2024, https://register.clinicaltrials.gov.

Functional dyspepsia (FD) is a condition characterized by persistent indigestion symptoms without a clear underlying cause. We investigated the effects on FD of Lacticaseibacillus paracasei HP7 (HP7), which was isolated from kimchi and is known to inhibit Helicobacter pylori. In a mouse model of loperamide-induced FD, HP7 administration significantly improved gastrointestinal (GI) motility and gastric emptying, as demonstrated by increased charcoal movement in the GI tract, decreased stomach weight, and the amount of remaining phenol red solution. HP7 administration significantly enhanced peristalsis by upregulating the expression of smooth muscle contraction-related genes, such as the 5HT4 receptor, anoctamin-1, ryanodine receptor 3, and smooth muscle myosin light-chain kinase. In addition, digestive factors, including GI regulatory hormones such as gastrin, gastric inhibitory peptide, and peptide YY, and the activity of digestive enzymes, such as amylase, trypsin, and lipase, were restored to normal levels. These results indicate that HP7 is a promising probiotic strain to alleviate FD symptoms by modulating peristalsis and digestive factors.

Medical advancements, including Helicobacter pylori eradication and antisecretory agents, have reduced peptic ulcer disease (PUD)-associated hospital admissions, mortality, and surgical interventions over the past 30 years. Surgery plays an important role in the treatment of life-threatening complications of PUD, such as bleeding, perforation, and gastric outlet obstruction, as well as for disease that is refractory to medical management. The article highlights the critical role of surgery in cases where medical therapy is insufficient or in the event of emergency complications arising from PUD.

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.

Impaired gastric accommodation is one of the most frequent symptoms of functional dyspepsia. The safety and efficacy of conventional treatments remain to be proven and alternative herbal therapies have been proposed to alleviate gastrointestinal symptoms. This preclinical study examined the role of herbal Amara extract (containing Artemisia absinthium, Centaurium erythraea, Cichorium intybus, Gentiana lutea, Juniperus communis, Achillea millefolium, Peucedanum ostruthium, Salvia officinalis, and Taraxacum extracts) on gastric (fundus) accommodation and the possible implication of muscarinic receptors in its regulation.

The effect of Amara extract on fundus motility was investigated in organ baths of smooth muscle strips isolated from the fundus of guinea pigs, and the role of the muscarinic receptor pathway was evaluated using functional and radioligand binding assays in cell lines expressing the M2 or M3 muscarinic receptor.

Amara extract inhibited carbachol-induced contraction of guinea pig smooth muscle strips in a dose-dependent manner. This relaxant effect was not affected by the M3 antagonist J-104129. Amara extract also inhibited M2, but not M3, receptor activity in CHO-K1 cells (IC50 219 μg mL-1), and specifically bound the M2 receptor (IC50 294 μg mL-1). Of the nine herbal components of Amara extract, Juniperus communis, P. ostruthium, and Salvia officinalis inhibited M2 receptor activity (IC50 32.0, 20.8, and 20.1 μg mL-1, respectively), and P. ostruthium was sufficient to reverse carbachol-induced ex vivo contraction of guinea pig fundic smooth muscles.

Amara extract relaxes gastric smooth muscles by inhibiting the M2 muscarinic receptor. This study suggests the potential benefit of Amara extract for patients with impaired gastric accommodation.

The present study aimed to evaluate the endoscopic findings of patients with dyspepsia in Ghaem Hospital, Mashhad, Iran.

This cross-sectional study collected endoscopic findings in patients with dyspepsia, including epigastric pain or heartburn, postprandial fullness, and early satiety from Ghaem Hospital from 2019 to 2020.

Totally, 743 patients were studied, and 42.3% (n=314) were male. The mean age was 46 years. Among participants, 85.6% (n=636) were included in the functional dyspepsia group, and the rest were included in the organic dyspepsia group. In the organic dyspepsia group, the highest frequency was related to peptic ulcer disease, with 7.2% (n=53). Moreover, the most common complaint was epigastric pain and heartburn. No significant association was found between comorbidities (P=0.083), smoking, and sex (P=0.532) with the risk of organic dyspepsia.

Dyspepsia is not necessarily accompanied by other comorbidities. The most mentioned chief complaint was epigastric pain or heartburn. Functional dyspepsia was the most common diagnosis in patients with dyspepsia, and the peptic ulcer was the leading cause of organic dyspepsia. There was no difference in the underlying cause of dyspepsia in the sexes.

Neuronal dysfunction is implicated in the pathophysiology of asthma and functional dyspepsia (FD). However, the relationship between these diseases remains unclear.

This study aimed to clarify the clinical implications of comorbid FD in asthma and to explore the unified pathway between asthma and FD by focusing on airway neuronal dysfunction.

Clinical indices and biomarkers, including capsaicin cough sensitivity (C-CS), were compared between patients with asthma with and without FD. C-CS was determined on the basis of capsaicin concentration that induced at least 2 coughs (C2) or 5 coughs (C5). Additionally, the associations of airway inflammation with airway innervation and gastrointestinal motility were evaluated in mouse models of type 2 airway inflammation.

Patients with asthma with FD had worse asthma control and cough severity and lower C2 and C5 thresholds than those without FD. The severity of FD symptoms was negatively correlated with C2 and C5 thresholds. FD and poor asthma control were predictors of heightened C-CS (defined as C5 ≤ 2.44 μmol) in asthma. A mouse model of papain-induced airway inflammation developed airway hyperinnervation and gastrointestinal dysmotility, and both pathologies were ameliorated by an anti-IL-33 antibody. Moreover, papain-induced gastrointestinal dysmotility was mitigated by silencing the airway sensory neurons using QX-314, a sodium channel blocker. Furthermore, sputum IL-33 levels were significantly elevated in patients with asthma with FD or heightened C-CS compared to their counterparts.

FD is significantly associated with airway neuronal dysfunction in asthma. IL-33-mediated airway neuronal dysfunction may contribute to the interaction between asthma and FD.

The Rome IV criteria for functional dyspepsia (FD) has strict requirements for symptom frequency and onset duration, making it difficult for patients to meet these criteria in clinical practice. This study aimed to investigate the impact of relaxing the Rome IV criteria on the diagnosis and symptom pattern of FD.

A cross-sectional, multi-center study was conducted involving 2935 consecutive broadly defined FD patients without positive findings on upper gastrointestinal endoscopy or routine examinations. Questionnaires were used to collect demographic and upper gastrointestinal symptom data. Symptom pattern was compared between Rome IV criteria defined FD patients and those defined by relaxed Rome IV criteria.

Only 22.2% of broadly defined FD patients rigorously fulfilled Rome IV criteria. No significant difference was found for proportion of patients with dyspeptic symptoms, dysmotility-like symptoms, reflux-like symptoms, as well as severity and onset frequency of dyspeptic symptoms (all P > 0.05), between patients who didn't fulfill Rome IV criteria for FD solely due to a duration of 3-6 months and Rome IV criteria defined FD patients. Patients with broadly defined postprandial distress syndrome (PDS) who didn't fulfill Rome IV criteria solely due to a symptom frequency of 1-2 days per week had significantly lower symptom severity (P < 0.001), but similar postprandial symptom characteristics compared to those defined by the Rome IV criteria.

A symptom duration criterion of 3 months may be sufficient for diagnosing FD. Reducing the symptom onset frequency to no less than 1 day per week in the Rome IV criteria for PDS does not affect its postprandial symptom characteristics.

We aimed to investigate the effect of removing milk and dairy products from diets on functional dyspepsia (FD) symptoms, as the aetiology remains unclear and new management approaches are needed.

This cross-sectional cohort study included 120 patients, with a mean age of 42.5 ± 12.3, of whom 77 (64.2 %) were female, with FD diagnosed by the Rome IV criteria. Patients were divided equally into two groups: those who eliminated milk and dairy products from their diet under the advice of a dietician without medical treatment and those who did not. The severity of symptoms was assessed using the gastrointestinal symptom rating scale (GSRS) at the beginning and end of a one-month period.

The restricted and unrestricted diet groups showed no significant differences in age, body mass index, symptom frequency and duration, weight changes, FD subtype, and gastroscopy results (p > 0.05). The diet group had more female patients (p = 0.01) and higher GSRS scores at the beginning (p = 0.01) but similar scores at the end of the study (p = 0.99). After one month, both groups had improved GSRS scores (p = 0.01), but the diet group had a more significant decrease in total symptom scores (p = 0.01) and in 7 of the 15 subsets (p < 0.05).

Of the 120 FD patients who followed up for one month, 60 who removed milk products had a more significant reduction in GSRS symptom score and 7 of the 15 symptom subset scores than 60 patients receiving an unrestricted diet.

Functional dyspepsia is a common gastrointestinal disease that is under-recognized and under-diagnosed. It is a complex disorder of gut-brain interaction with no FDA-approved treatment options. The purpose of this review is to highlight updates in the proposed pathophysiology and present new data regarding potential therapies for functional dyspepsia.

Alterations in the intestinal microbiome and integrity of the intestinal membrane may play a crucial role in the pathogenesis of functional dyspepsia. The low FODMAP diet, in addition to modulating the microbiome with antibiotics and probiotics, are targets for large future studies. Novel methods of delivery of gut-brain therapies have shown promising results, especially virtual reality.

The pathophysiology and management of functional dyspepsia is complex and there is still much unknown; however, continued research is identifying new targets for treatment. New and more targeted treatment options provide clinicians a variety of tools to offer patients with functional dyspepsia.

NOVAponin, a functional health food derived from Dolichos lablab Linne extract improves gastric mucosal injury and increases regeneration and proliferation. This study aims to investigate the efficacy and safety of NOVAponin in individuals with mild functional dyspepsia (FD).

In this single-center, double-blind, randomized clinical trial, 131 patients with FD meeting the Rome IV criteria were enrolled. Changes in the gastrointestinal symptom rating scale (GSRS), FD-related quality of life (FD-QoL), gastrointestinal symptom (GIS) scores, inflammatory and anti-inflammatory markers, and adverse effects before and after administration were compared.

After 12 weeks of administration, GSRS upper abdominal symptom scores were significantly improved in the test group compared to the control group (-5.30 ± 0.60 vs -2.35 ± 0.56, P < 0.001). GSRS upper abdominal symptom scores (-5.13 ± 0.55 vs -1.92 ± 0.44, P < 0.001), GSRS total scores (-7.02 ± 0.91 vs -3.33 ± 0.73, P < 0.001), GIS total scores (-11.21 ± 0.53 vs -6.65 ± 0.70, P < 0.001) after 6 weeks of administration, GSRS total scores (-7.54 ± 0.94 v. -3.31 ± 0.85, P < 0.001), GIS total scores (-11.90 ± 0.52 vs -7.61 ± 0.73, P < 0.001), and FD-QoL total scores (-11.41 ± 1.75 vs -5.55 ± 1.20, P = 0.007) after 12 weeks of administration also showed significant differences between groups. The differences were slightly more pronounced in epigastric pain syndrome subtypes and in females than the others, although more females were assigned to the test group. There were no significant changes in inflammatory and anti-inflammatory markers or adverse reactions.

NOVAponin significantly improved mild FD symptoms especially in epigastric pain syndrome subtype and in females, and was found to be safe.

To investigate the potential link between gut microbiota and functional dyspepsia (FD). Genome-wide association studies (GWAS) of gut microbiota and FD were used in Mendelian randomization (MR) research. Using the GWAS of 18,340 people, instrumental variables related to gut microbiota as an exposure factor were identified. In a GWAS investigation, 189,695 control individuals and 4376 FD patients were included as outcome variables. The primary analysis technique was inverse variance weighted analysis. The reliability of MR analysis results is tested using sensitivity analysis. Two-sample Mendelian randomization analysis revealed the presence of 7 gut microbiota associated to FD. In the inverse variance weighted analysis method, Order Erysipelotrichales (odds ratio (OR): 1.301; 95% confidence interval (CI): 1.016, 1.665; P = .037), Family Erysipelotrichales (OR: 1.301; 95% CI: 1.016, 1.665; P = .037), Genus Haemophilus (OR: 1.236; 95% CI 1.059, 1.442; P = .007), Genus Ruminiclostridium 9 (OR: 1.422; 95% CI: 1.078, 1.877; P = .013), Genus Lachnospiraceae NK4A 136 group (OR: 1.297; 95% CI: 1.059, 1.589; P = .012) was positively associated with FD. Class Gammaproteobacteria (OR: 0.705; 95% CI: 0.522, 0.952; P = .022) and Genus Erysipelatoclostridium (OR: 0.747; 95% CI: 0.628, 0.888; P = .001) were found to be inversely related to FD. There was no evidence of pleiotropy or heterogeneity in the sensitivity analysis. Our research provides evidence for a possible link between FD and a number of gut microbiota. The role that gut microbiota plays in the development of FD requires more investigation.

The use of neuromodulators is prevalent in various functional gastrointestinal disease. However, data concerning the outcomes of these treatments in functional esophageal disorders (FED) remains limited and inadequate.

The aim of the present study is to examine the efficacy of central neuromodulators in FED.

We searched PubMed, EMBASE, and the Cochrane library databases from inception to April 2023. Randomized controlled trials that compared the effects of neuromodulators and placebos on FED are included. Primary outcome is the symptom improvement, and Rome IV criteria is used to assess eligible studies.

Eleven randomized controlled studies (three for functional chest pain, four for reflux hypersensitivity/functional heartburn, three for globus, and one for functional dysphagia) were included in the final analysis. Neuromodulators reduced chest pain by 52%-71% in patients with functional chest pain, and alleviated symptom by 46%-75% in patients with globus (n = 3, Odds ratio 6.30, 95% confidence interval 4.17-9.50). However, the results were inconsistent for reflux hypersensitivity and functional heartburn. There was a lack of convincing evidence to support the use of neuromodulators for functional dysphagia. The use of neuromodulators did not have a significant impact on the quality of life.

Functional chest pain and globus may potentially benefit from the use of neuromodulators, but their effectiveness for functional dysphagia, functional heartburn and reflux hypersensitivity remains controversial. More controlled trials are needed to confirm the therapeutic effects on these conditions.

Functional dyspepsia (FD) is prevalent worldwide and is associated with gastrointestinal inflammation, mucosal anomalies, and shifts in microbiota metabolites like short chain fatty acids. This study assesses the efficacy of Jing Si herbal tea (JSHT) in alleviating FD symptoms, psychological distress, and influencing metabolites.

Adults with FD based on Rome IV criteria were included. Participants underwent physical and psychological evaluations, pre-treatment blood sampling, and were randomly assigned to JSHT or placebo groups for four weeks. Post-treatment, evaluations and Liquid Chromatography-Mass Spectrometry for gut metabolites were done. Successful response was defined by a 50% symptom reduction. Symptom intensity, sleep, depression, anxiety, and stress were measured using questionnaires.

26 patients (median age 55.5 years, range 22-77 years, 60.6% female) were studied. Both JSHT and placebo groups were similar at baseline. JSHT showed a higher response rate (69.2%) than placebo (23.1%, P = 0.018). JSHT recipients experienced notable reduction in upper gastrointestinal symptoms and anxiety (P = 0.005; P = 0.037). Increased serum butyrate was observed in improved patients (P = 0.01), whereas no major changes were detected in the placebo group.

Four weeks of JSHT treatment ameliorated FD symptoms and anxiety, potentially linked to increased serum butyrate. This study suggests that JSHT has potential therapeutic role in patients with FD.

Gastrointestinal (GI) disorders are highly prevalent and severely diminish life quality. It is yet unknown which dietary pattern is optimal for the prevention of GI disorders. Among 141 450 participants from UK Biobank with a median follow-up of 15 years, we comprehensively assessed 13 dietary patterns in relation to 6 GI disorders. Multivariable Cox proportional hazards models demonstrated that adherence to healthy diets was associated with lower risk of GI disorders, with the strongest associations observed for the Dietary Approaches to Stop Hypertension (DASH) diet (HRQ4 vs. Q1 = 0.85, 95% CI: 0.81, 0.88), the Alternate Mediterranean Diet (AMED) (HRQ4 vs. Q1 = 0.85, 95% CI: 0.81, 0.88), and the Alternate Healthy Eating Index-2010 (AHEI-2010) (HRQ4 vs. Q1 = 0.86, 95% CI: 0.82, 0.89). AHEI-2010 (HRs ranging from 0.76 to 0.90) and DASH (HRs ranging from 0.75 to 0.88) showed inverse associations with every individual GI disorder. Furthermore, comorbidities decreased significantly in number with higher AMED and DASH diet scores (P for trend <0.001). Finally, the associations of AHEI-2010, AMED and DASH with GI disorders diminished most intensely after removing the component of fruits or whole grains. The combined intake of fruits and whole grains was inversely associated with the risk of overall GI disorders (HRT3 vs. T1 = 0.89, 95% CI: 0.86, 0.93). In conclusion, AHEI-2010 and DASH were the most recommended dietary patterns for the prevention of GI disorders. Fruits and whole grains are the most significant contributors to the protective effect.

Dyspeptic symptoms belong to the most frequent reasons to seek medical advice and are a burden both for the individual affected and the healthcare system. In Japan, the traditional herbal Kampo prescription rikkunshito has proven benefit for this indication.

In a prospective, multicentre, non-interventional study (NIS), the effectiveness, safety, and tolerability of a two-week treatment with the registered rikkunshito extract product YamatoGast was assessed in German patients with an acute episode of dyspeptic symptoms of functional origin under real-world conditions. The primary endpoint was the responsiveness to treatment assessed by the overall treatment effect (OTE) score. Secondary endpoints were the change in severity of dyspeptic symptoms and the change in quality of life (QoL). Safety evaluation was based on reported adverse drug reactions, drug compliance, and ratings of tolerability by physicians and patients.

Sixty-six patients were enrolled (mean age 48.9 years, 74% females). The treatment was well tolerated and highly beneficial, as expressed by pronounced responder rates of 78.9% for the primary endpoint OTE. All secondary endpoints were also met. The severity of dyspeptic symptoms significantly improved by 62-77% compared to baseline, confirmed by a remarkable improvement of QoL. Significant symptom relief started from the third day of treatment onwards.

In this non-interventional study, two-week treatment with YamatoGast resulted in a significant improvement of dyspeptic symptoms and was associated with high patient response and satisfaction. YamatoGast was confirmed as a safe and clinically relevant therapeutic option for patients suffering upper gastrointestinal complaints in routine practice.

Chronic gastritis (CG) is a common gastrointestinal disorder characterized by inflammation of the stomach lining. Liver-stomach disharmony (LSD) syndrome is believed to contribute to CG symptoms.

To evaluate the efficacy and safety of microcosmic syndrome differentiation and Chinese herbal medicine (CHM) treatment in patients with CG and LSD syndrome.

Sixty-four patients with CG and LSD syndrome were randomly divided into two groups: The treatment group received CHM based on microcosmic syndrome differentiation and the control group received conventional Western medicine. The treatment course lasted 12 wk. The primary outcome was improvement in dyspeptic symptoms, measured using the Nepean Dyspepsia Index. The secondary outcomes included the improvement rate of endoscopic findings, histopathological findings, and microcosmic syndrome scores and the incidence of adverse events.

After 12 wk of treatment, the treatment group showed significantly greater improvement in dyspeptic symptoms than the control group (93.75% vs 65.63%, P < 0.01). The treatment group also showed a significantly higher improvement rate in endoscopic findings than the control group (81.25% vs 53.13%, P < 0.05). The improvement rates of histopathological findings and microcosmic syndrome scores were not significantly different between the two groups (P > 0.05). No serious adverse events were observed in either group.

Microcosmic syndrome differentiation and CHM treatment can effectively improve dyspeptic symptoms and endoscopic findings in patients with CG and LSD syndrome and have a good safety profile. Further studies with larger sample sizes and longer follow-up periods are required to confirm the long-term efficacy and mechanism of action of this treatment.

Herbal products are widely used to treat patients with disorders of gut brain interaction but clinical efficacy and safety data for treatments lasting >4 weeks are widely lacking. We evaluated the efficacy and safety of 8 weeks of treatment with the herbal combination product STW 5-II for patients with functional dyspepsia (FD) meeting Rome II criteria. We also conducted a post hoc analysis including patients meeting Rome IV criteria for FD and evaluated the effect of the G-protein beta 3 (GNB3) subunit polymorphism (C825T) on therapeutic response.

This multicenter, placebo-controlled, double-blind study included 272 FD patients meeting Rome II criteria in the intention-to-treat cohort and 266 meeting Rome IV criteria. We used the validated Gastrointestinal Symptom Score (GIS) to assess GI symptoms, defining response rate as the proportion of patients with ≥50% GIS improvement in at least three of four assessments.

After 8 weeks, the response rate was significantly higher in the STW 5-II group versus placebo (61.2% vs 45.1%, P = 0.008). Mean GIS non-significantly improved with STW 5-II treatment (7.9 ± 4.41 vs 6.7 ± 4.91 with placebo; P = 0.07). In the Rome IV subgroup analysis, STW 5-II yielded a better response rate (P = 0.01) versus placebo and greater postprandial distress symptom improvement (P = 0.04) versus placebo. Safety parameters did not differ between groups, and GNB3 status was not linked with therapeutic response.

STW 5-II is efficacious, with no observed safety signals at up to 8 weeks of treatment in patients with FD meeting Rome II or IV criteria.

Functional dyspepsia is a common functional gastrointestinal disorder that is often challenging to treat. Psychotherapeutic interventions have been proposed as an alternative or adjunctive approach to conventional treatments, but their efficacy remains unclear.

This systematic review and meta-analysis aimed to evaluate the efficacy of psychotherapeutic interventions in the treatment of functional dyspepsia.

A comprehensive search of electronic databases was conducted, from inception to March 2023, for randomized controlled trials (RCTs) that evaluated the effects of psychotherapeutic interventions on patients with functional dyspepsia. The primary outcome measures were gastrointestinal symptoms, quality of life, depression, and anxiety. Data were extracted and analyzed using Review Manager 5.3 software. The risk of bias of the included studies was assessed using the Cochrane Risk of Bias tool.

Sixteen RCTs comprising 1550 patients with functional dyspepsia were included in the meta-analysis. The types of psychotherapeutic interventions used in the included studies were cognitive-behavioral therapy (CBT), hypnotherapy, and mindfulness-based stress reduction (MBSR). The control groups were usual care, placebo, supportive therapy, or no treatment. The meta-analysis showed that psychotherapeutic interventions had a significant effect on reducing gastrointestinal symptoms,depression and anxiety in patients with functional dyspepsia. However, no significant improvement was observed in the quality-of-life scores of patients who received psychotherapeutic interventions compared to those in the control group.

Psychotherapeutic interventions, such as CBT, hypnotherapy, and MBSR, could be a useful adjunct to conventional treatments for functional dyspepsia, as they were found to significantly reduce gastrointestinal symptoms and anxiety in patients. However, further studies are needed to assess the long-term effects and generalizability of these interventions.

Vagal nerve stimulation (VNS) can be used to modulate gastrointestinal motility, inflammation, and nociception. However, it remains unclear whether VNS is effective in adult patients with functional dyspepsia (FD). We investigated the effectiveness of transcutaneous auricular VNS (taVNS) in patients with FD.

Consecutive patients with FD meeting Rome IV criteria with modified FD Symptom Diary score ≥10 were enrolled. Patients were randomly allocated to 10-Hz taVNS (V10 group), 25-Hz taVNS (V25 group), or sham group, with 30 minutes of treatment twice a day for 4 weeks. The primary outcome was the response rate at week 4, defined as the proportion of patients whose modified FD Symptom Diary score was reduced ≥5 when compared with the baseline. Secondary outcomes included adequate relief rate and adverse events.

A total of 300 patients were randomized to V10 (n = 101), V25 (n = 99), and sham groups (n = 100). After 4 weeks of treatment, V10 and V25 groups had a higher response rate (81.2% vs 75.9% vs 47%, both P < 0.001) and adequate relief rate (85.1% vs 80.8% vs 67%, both P < 0.05) compared with the sham group. There was no significant difference between V10 and V25 in response rate and adequate relief rate (both P > 0.05). The efficacy of taVNS (both 10 and 25 Hz) lasted at week 8 and week 12 during follow-up period. Adverse events were all mild and comparable among the 3 groups (1%-3%).

Our study firstly showed that 4-week taVNS (both 10 and 25 Hz) was effective and safe for the treatment of adult FD ( clinicaltrials.gov number: NCT04668534).

Almost 80% of individuals with functional dyspepsia experience meal-related symptoms and are diagnosed with postprandial distress syndrome (PDS). However, studies evaluating dietary modifications in PDS are sparse. We performed a single-center randomized trial comparing reassurance and diagnostic explanation (RADE) with or without traditional dietary advice (TDA) in PDS.

Following a normal upper gastrointestinal endoscopy, individuals with PDS were randomized to a leaflet providing RADE ± TDA; the latter recommending small, regular meals and reducing the intake of caffeine/alcohol/fizzy drinks and high-fat/processed/spicy foods. Questionnaires were completed over 4 weeks, including self-reported adequate relief of dyspeptic symptoms, and the validated Leuven Postprandial Distress Scale (LPDS), Gastrointestinal Symptom Rating Scale, and Nepean Dyspepsia Index for quality of life. The primary endpoint(s) to define clinical response were (i) ≥50% adequate relief of dyspeptic symptoms and (ii) >0.5-point reduction in the PDS subscale of the LPDS (calculated as the mean scores for early satiety, postprandial fullness, and upper abdominal bloating).

Of the 53 patients with PDS, 27 were assigned RADE-alone and 26 to additional TDA. Baseline characteristics were similar between groups, with a mean age of 39 years, 70% female, 83% white British, and coexistent irritable bowel syndrome in 66%. The primary endpoints of (i) adequate relief of dyspeptic symptoms were met by 33% (n = 9) assigned RADE-alone versus 39% (n = 10) with TDA; p-value = 0.70, while (ii) a reduction of >0.5 points in the PDS subscale was met by 37% (n = 10) assigned RADE-alone versus 27% (n = 7) with TDA; p-value = 0.43. Response rates did not differ according to irritable bowel syndrome status. There were no significant between-group changes in the gastrointestinal symptom rating scale and dyspepsia quality of life.

This study of predominantly white British patients with PDS found the addition of TDA did not lead to significantly greater symptom reduction compared with RADE alone. Alternate dietary strategies should be explored in this cohort.

Introduction: The purpose of this study was to identify the chemical components of Massa Medicata Fermentata (MMF) in different fermentation methods, analyze its regulatory effects on gastrointestinal propulsion and intestinal flora in mice with food accumulation, and further explore its mechanism of action in the treatment of dyspepsia. Methods: The chemical compositions of three kinds of MMF were identified using the UPLC-Q- Exactive Orbitrap mass spectrometer. A model of spleen deficiency and food accumulation in mice was established. The gastric emptying rate and intestinal propulsion rate were calculated, serum gastrin concentration and cholinesterase activity were measured, and 16S rRNA microbial detection was performed in different groups of mouse feces. Results: The results showed that a total of 95 chemical components were identified from the three MMF extracts, 62 of which were the same, but there were differences in flavonoids and their glycosides, organic acids, and esters. MMF, PFMMF, and commercial MMF could all significantly improve the gastric emptying rate, intestinal propulsion rate, and GAS concentration in the serum of model mice; PFMMF has a better effect, while there was no significant difference in cholinesterase activity among the groups (p > 0.05). The 16S rRNA sequencing results showed that the MMF and PFMMF could increase the content of beneficial bacteria Bacteroidetes and decrease the pathogenic bacteria Verrucomicrobia in the intestines of model mice, while the commercial MMF could not. Discussion: Studies suggest that MMF has a variety of possible mechanisms for improving food accumulation and treating gastrointestinal dyspepsia, which provides reference value for the quality evaluation and clinical application of MMF.

To compare the efficacy of Duloxetine and Nortriptyline in alleviating the symptoms of severity, anxiety, depression and quality of life in patients with functional dyspepsia (FD).

We conducted a single-blinded 3-month trial of Duloxetine 20-30 mg daily in 20 patients and Nortriptyline 25 mg daily in 25 FD patients. The primary outcome measure was the severity of FD symptoms by Gastrointestinal symptoms rating scale. Secondary measures included Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, and Nepean Dyspepsia Index. the patients were measured in 3 stages.

45 patients with FD with a mean age of 37.18 ± 10.62 years participated in the study. The severity of symptoms was significantly lower in the Nortriptyline group than in the Duloxetine group after three months (p = 0.031). The level of anxiety (p = 0.049), depression (p = 0.045) and quality of life (p = 0.046) improved significantly after three months in the Duloxetine group compared to Nortriptyline. Mediation analysis using linear regression revealed a significant mediator role for anxiety. This mediation analysis revealed a 21.13% reduction in anxiety in the Duloxetine group.

While both medications demonstrated efficacy, Nortriptyline appeared to be superior in symptom reduction. Duloxetine exhibited more advantages compared to Nortriptyline in addressing anxiety and depression and enhancing the overall quality of life. Also, Duloxetine may have a noteworthy impact, contributing to a 20% reduction in FD symptoms by lowering anxiety levels.

https://en.irct.ir/trial/65512.

Current treatment for functional dyspepsia (FD) has limited and unsustainable efficacy. Probiotics have the sustainable potential to alleviate FD. This randomized controlled clinical trial (Chinese Clinical Trial Registry, ChiCTR2000041430) assigned 200 FD patients to receive placebo, positive-drug (rabeprazole), or Bifidobacterium animalis subsp. lactis BL-99 (BL-99; low, high doses) for 8-week. The primary outcome was the clinical response rate (CRR) of FD score after 8-week treatment. The secondary outcomes were CRR of FD score at other periods, and PDS, EPS, serum indicators, fecal microbiota and metabolites. The CRR in FD score for the BL-99_high group [45 (90.0%)] was significantly higher than that for placebo [29 (58.0%), p = 0.001], BL-99_low [37 (74.0%), p = 0.044] and positive_control [35 (70.0%), p = 0.017] groups after 8-week treatment. This effect was sustained until 2-week after treatment but disappeared 8-week after treatment. Further metagenomic and metabolomics revealed that BL-99 promoted the accumulation of SCFA-producing microbiota and the increase of SCFA levels in stool and serum, which may account for the increase of serum gastrin level. This study supports the potential use of BL-99 for the treatment of FD.

Current treatment for functional dyspepsia (FD) has limited and unsustainable efficacy. Probiotics have the sustainable potential to alleviate FD. This randomized controlled clinical trial (Chinese Clinical Trial Registry, ChiCTR2000041430) assigned 200 FD patients to receive placebo, positive-drug (rabeprazole), or Bifidobacterium animalis subsp. lactis BL-99 (BL-99; low, high doses) for 8-week. The primary outcome was the clinical response rate (CRR) of FD score after 8-week treatment. The secondary outcomes were CRR of FD score at other periods, and PDS, EPS, serum indicators, fecal microbiota and metabolites. The CRR in FD score for the BL-99_high group [45 (90.0%)] was significantly higher than that for placebo [29 (58.0%), p = 0.001], BL-99_low [37 (74.0%), p = 0.044] and positive_control [35 (70.0%), p = 0.017] groups after 8-week treatment. This effect was sustained until 2-week after treatment but disappeared 8-week after treatment. Further metagenomic and metabolomics revealed that BL-99 promoted the accumulation of SCFA-producing microbiota and the increase of SCFA levels in stool and serum, which may account for the increase of serum gastrin level. This study supports the potential use of BL-99 for the treatment of FD.

A combination of multiple tests was introduced to noninvasively investigate the differences in pathophysiologies among functional dyspepsia (FD) subgroups, including postprandial distress syndrome (PDS), epigastric pain syndrome (EPS), and overlap.

It has not been extensively evaluated whether different pathophysiologies are involved in FD subgroups.

This multicenter study included 364 FD patients fulfilling Rome IV criteria and 47 healthy controls. A combined noninvasive gastric and autonomic function test was performed: The electrogastrogram and electrocardiogram were recorded simultaneously in the fasting state and after a drink test. Symptoms after drinking were recorded using visual analog scale.

(1) Compared with HC, FD patients showed a decreased maximum tolerable volume (MTV) ( P <0.01) and percentage of normal gastric slow waves [normal gastric slow waves (%NSW)] ( P <0.01), and increased postdrinking symptoms, anxiety ( P <0.01), and depression ( P <0.01). The drink reduced %NSW in both FD patients and HC; however, the effect was more potent in patients. (2) The PDS and overlap groups displayed a reduced MTV ( P <0.05). The overlap group exhibited a higher symptom score at 30 minutes after drinking, and higher anxiety and depression scores, and a higher sympathovagal ratio than the EPS ( P <0.05 for all) and PDS ( P <0.01 for all). (3) In the PDS subgroup, the MTV, postprandial sympathovagal ratio, and depression were associated with the overall dyspepsia symptom scale (DSS, P =0.034, 0.021, 0.043, respectively). No significant associations were found in the other 2 subgroups.

The combination of multiple tests can detect pathophysiological abnormities in FD patients. Overall, patients with overlap symptoms display more severe pathophysiologies.

Functional dyspepsia is a form of dyspepsia lacking in clear causes following clinical assessment. Dyspepsia is characterized by episodic or persistent abdominal pain or discomfort of the upper gastrointestinal (GI) tract. Its onset has been linked with a deficiency or dysfunction of digestive enzymes. Thus, consumption of digestive multi-enzymatic preparations may be effectively used for the reduction of symptoms. The aim of this study is to assess the effectiveness and tolerability of the supplementation of a normal diet with a multi-enzyme blend obtained from fungal fermentation, in a randomized, placebo-controlled, double-blind, clinical trial. Enrolled subjects (n = 120, male: 63, female: 57), aged 18-59 years, were randomized (allocation ratio 1:1) to receive either 2 capsules per day of the food supplement (containing 200 mg of the multi-enzyme blend/capsule) or placebo, for 2 months. The primary outcome of the study (i.e., improvements in quality of life) was evaluated by the Nepean Dyspepsia Index-SF (NDI-SF) questionnaire, while the secondary outcomes (i.e., severity of pain and the quality of sleep) were assessed through the Visual Analogue Scale (VAS) and Pittsburgh Sleep Quality Index (PSQI) questionnaire. The results showed an improvement in NDI-SF1, NDI-SF2-5, VAS, and PSQI scores in subjects treated with the multi-enzyme blend, indicating an improvement in quality of life and of sleep, and a decreased severity of pain, following the supplementation with digestive enzymes, without side effects. In conclusion, treatment with digestive enzymes was found to be effective in the reduction of functional dyspepsia symptoms and in the improvement of sleep quality, and is well-tolerated.

There is no study evaluating the association between exercise and functional dyspepsia (FD) based on the Rome IV criteria. We aimed to investigate the prevalence of FD and evaluate the association between exercise and FD based on Rome IV criteria among a sample of Chinese armed police recruits.

An on-site questionnaire survey on FD among a sample of Chinese armed police recruits was conducted based on the Rome IV criteria in 2021. Potential confounders included age, body mass index (BMI), race, marriage, education, smoking, and drinking variables were adjusted.

A total of 2594 recruits were enrolled, including 46 FD participants and 2548 non-FD participants. In the model adjusted for all demographic variables among participants excluding irritable bowel syndrome (IBS) and functional constipation (FC), compared with no exercise participants, 1 h < each exercise time ≤ 2 h (OR = 0.15, 95% CI: 0.03-0.77, P = 0.0230) was inversely associated with FD and compared with no exercise participants, mild exercise (OR = 0.09, 95% CI: 0.01-0.71, P = 0.0220) was significantly inversely associated with FD.

The incidence rate of FD in this sample Chinese armed police recruits was 1.77%, and 1 h < each exercise time ≤ 2 h and mild intensity exercise were independently inversely associated with FD. However, the causal relationship needs to be verified by further randomized controlled trials.

The commonest medications prescribed in functional dyspepsia are prokinetic agents, specifically domperidone. However, its administration at times elevates serum prolactin levels, which can lead to pathological hyperprolactinemia. The present study investigated the effect of 28 days of 30 mg domperidone therapy on prolactinemia in functional dyspepsia patients. We recruited 97 patients (60 men and 37 women, aged 18-80 years) who had functional dyspepsia diagnosed as per the Rome IV criteria. After taking a preliminary clinical history, we measured and compared serum prolactin levels at day 'zero' and day 'twenty-eight'. We found increased prolactin levels from day '0' to day '28' after treatment with domperidone in functional dyspepsia patients, specifically in male participants aged less than 40 years, who are married and belong to middle socioeconomic status. The most common functional dyspepsia symptom found was pain in the epigastric region. To conclude, our pragmatic domperidone-induced-hyperprolactinemia link warrants this side effect to be robustly taken into account while treating functional dyspepsia patients with domperidone.

The effects of Helicobacter pylori eradication on gastric mucosa-colonizing microbes in patients with functional dyspepsia (FD) remain unclear. Here, we explored microbial variation induced by H. pylori infection and eradication treatment in FD patients. Gastric microbial abundance and diversity were significantly reduced in the H. pylori-infected FD patients. Eradication treatment increased alpha and beta diversity of gastric mucosa-colonizing microbes, and promoted the expansion of several probiotic microbes, such as Leuconostoc mesenteroides, which exhibited a matched antagonistic performance against H. pylori. Significant variation was observed in gastric mucosa-colonizing microbes between H. pylori-positive and H. pylori-negative FD patients. Eradication treatment induced microbial diversity recovery and may provide sufficient nutrition and space for probiotic microbes, such as Leuconostoc mesenteroides.

In the treatment of upper GI endoscopy-negative patients with heartburn and epigastric pain or burning, antacids, antireflux agents, and mucosal protective agents are widely used, alone or as add-on treatment, to increase response to proton-pump inhibitors, which are not indicated in infancy and pregnancy and account for significant cost expenditure.

In this randomized, controlled, double-blind, double-dummy, multicenter trial assessing the efficacy and safety of mucosal protective agent Poliprotect (neoBianacid, Sansepolcro, Italy) vs omeprazole in the relief of heartburn and epigastric pain/burning, 275 endoscopy-negative outpatients were given a 4-week treatment with omeprazole (20 mg q.d.) or Poliprotect (5 times a day for the initial 2 weeks and on demand thereafter), followed by an open-label 4-week treatment period with Poliprotect on-demand. Gut microbiota change was assessed.

A 2-week treatment with Poliprotect proved noninferior to omeprazole for symptom relief (between-group difference in the change in visual analog scale symptom score: [mean, 95% confidence interval] -5.4, -9.9 to -0.1; -6.2, -10.8 to -1.6; intention-to-treat and per-protocol populations, respectively). Poliprotect's benefit remained unaltered after shifting to on-demand intake, with no gut microbiota variation. The initial benefit of omeprazole was maintained against significantly higher use of rescue medicine sachets (mean, 95% confidence interval: Poliprotect 3.9, 2.8-5.0; omeprazole 8.2, 4.8-11.6) and associated with an increased abundance of oral cavity genera in the intestinal microbiota. No relevant adverse events were reported in either treatment arm.

Poliprotect proved noninferior to standard-dose omeprazole in symptomatic patients with heartburn/epigastric burning without erosive esophagitis and gastroduodenal lesions. Gut microbiota was not affected by Poliprotect treatment. The study is registered in Clinicaltrial.gov (NCT03238534) and the EudraCT database (2015-005216-15).

Functional dyspepsia (FD) is a multifactorial disorder. Helicobacter pylori (H. pylori)-related dyspepsia (HpD) may be considered a separate entity. Duodenal eosinophilia is a potential pathogenic mechanism in FD. However, the impact of duodenal eosinophilia and host genetic polymorphism of innate and pro-inflammatory cascade, nucleotide-binding oligomerization domain 1 (NOD-1), and interleukin-1 beta (IL-1β) in HpD was not explored.

To evaluate the association of NOD1-796G>A and IL-1B-511C>T gene variants and low-grade duodenal eosinophilia in HpD.

A multicenter cross-sectional study was conducted. A total of 253 patients who met Rome-IV criteria were selected before upper endoscopy and 98 patients were included after unremarkable upper endoscopy and positive H. pylori in gastric biopsies were assessed. Clinical parameters, H. pylori cagA and duodenal histology, were evaluated.

Sixty-four (65%) patients had epigastric pain syndrome (EPS), 24 (25%) postprandial distress syndrome (PDS), and 10 (10%) EPS/PDS overlap. FD subtypes were not associated with NOD1-796G>A and IL-1B-511C>T gene variants. Low-grade duodenal eosinophilia was significantly increased in NOD1-796 GG versus single A-allele, but not in IL-1B-511 single T-allele or CC-allele. This association is dependent of cagA infection, since harboring cagA strain was significantly associated with low-grade duodenal eosinophilia with isolated variants NOD1-796 GG and IL-1B-511 single T-allele, but not without cagA. When we performed combined polymorphism analysis with NOD1-796 GG/IL-1B-511 single T-allele, a synergistic effect on low-grade duodenal eosinophilia was found between these two loci irrespective of cagA strain status in HpD.

Our findings suggest that low-grade duodenal eosinophilia is significantly associated with NOD1-796 GG allele specially in cagA strain and with allelic combination NOD1-796 GG/IL-1B-511 single T-allele independent of cagA strain infection in HpD patients.

Proton pump inhibitors (PPIs) have been available for over three decades and are among the most commonly prescribed medications. They are effective in treating a variety of gastric acid-related disorders. They are freely available and based on current evidence, use of PPIs for inappropriate indications and duration appears to be common. Over the years, concerns have been raised on the safety of PPIs as they have been associated with several adverse effects. Hence, there is a need for PPI stewardship to promote the use of PPIs for appropriate indication and duration. With this objective, the Indian Society of Gastroenterology has formulated guidelines on the rational use of PPIs. The guidelines were developed using a modified Delphi process. This paper presents these guidelines in detail, including the statements, review of literature, level of evidence and recommendations. This would help the clinicians in optimizing the use of PPIs in their practice and promote PPI stewardship.