Patient-Reported Outcomes in Disorders of Gut-Brain Interaction.

Disorders of gut-brain interaction are characterized by chronic gastrointestinal symptoms in the absence of abnormal endoscopic or radiologic findings or objective biomarkers that can be identified during routine clinical evaluation. The assessment of the symptom pattern and severity, therefore, is the key modality to evaluate the presence, impact, and evolution of these conditions, for both clinical and regulatory purposes. Patient-reported outcomes are structured symptom assessment questionnaires designed to evaluate symptom patterns, quantify severity of symptoms, and evaluate response to treatment at follow-up. This review provides an overview of currently available patient-reported outcomes for evaluating the main disorders of gut-brain interaction, specifically, functional dyspepsia; irritable bowel syndrome; and chronic constipation. It summarizes their content, level of validation for clinical practice and for research, and the regulatory approach to these conditions. Expected future developments and need for further research on patient-reported outcomes for these and other disorders of gut-brain interaction are highlighted.

Intestinal Permeability in Disorders of Gut-Brain Interaction: From Bench to Bedside.

Intestinal barrier function lies at a critical interface of a range of peripheral and central processes that influence disorders of gut-brain interactions (DGBI). Although rigorously tested, the role of barrier dysfunction in driving clinical phenotype of DGBI remains to be fully elucidated. In vitro, in vivo, and ex vivo strategies can test various aspects of the broader permeability and barrier mechanisms in the gut. Luminal mediators of host, bacterial, and dietary origin can influence the barrier function and a disrupted barrier can also influence the luminal milieu. Critical to our understanding is how barrier dysfunction is influenced by stress and other comorbidities that associate with DGBI and the crosstalk between barrier and neural, hormonal, and immune responses. Additionally, the microbiome's significant role in the communication between the brain and gut has led to the integrative model of a microbiome gut-brain axis with reciprocal interactions between brain networks and networks composed of multiple cells in the gut, including immune cells, enterochromaffin cells, gut microbiota and the derived luminal mediators. This review highlights the techniques for assessment of barrier function, appraises evidence for barrier dysfunction in DGBI including mechanistic studies in humans, as well as provides an overview of therapeutic strategies that can be used to directly or indirectly restore barrier function in DGBI patients.

Comorbid functional dyspepsia reflects IL-33-mediated airway neuronal dysfunction in asthma.

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

Postprandial symptoms in disorders of gut-brain interaction and their potential as a treatment target.

Postprandial, or meal-related, symptoms, such as abdominal pain, early satiation, fullness or bloating, are often reported by patients with disorders of gut-brain interaction, including functional dyspepsia (FD) or irritable bowel syndrome (IBS). We propose that postprandial symptoms arise via a distinct pathophysiological process. A physiological or psychological insult, for example, acute enteric infection, leads to loss of tolerance to a previously tolerated oral food antigen. This enables interaction of both the microbiota and the food antigen itself with the immune system, causing a localised immunological response, with activation of eosinophils and mast cells, and release of inflammatory mediators, including histamine and cytokines. These have more widespread systemic effects, including triggering nociceptive nerves and altering mood. Dietary interventions, including a diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols, elimination of potential food antigens or gluten, IgG food sensitivity diets or salicylate restriction may benefit some patients with IBS or FD. This could be because the restriction of these foods or dietary components modulates this pathophysiological process. Similarly, drugs including proton pump inhibitors, histamine-receptor antagonists, mast cell stabilisers or even tricyclic or tetracyclic antidepressants, which have anti-histaminergic actions, all of which are potential treatments for FD and IBS, act on one or more of these mechanisms. It seems unlikely that food antigens driving intestinal immune activation are the entire explanation for postprandial symptoms in FD and IBS. In others, fermentation of intestinal carbohydrates, with gas release altering reflex responses, adverse reactions to food chemicals, central mechanisms or nocebo effects may dominate. However, if the concept that postprandial symptoms arise from food antigens driving an immune response in the gastrointestinal tract in a subset of patients is correct, it is paradigm-shifting, because if the choice of treatment were based on one or more of these therapeutic targets, patient outcomes may be improved.

Prevalence of irritable bowel syndrome and functional dyspepsia after acute gastroenteritis: systematic review and meta-analysis.

OBJECTIVE: Disorders of gut-brain interaction may arise after acute gastroenteritis. Data on the influence of pathogen type on the risk of postinfection IBS (PI-IBS), as on postinfection functional dyspepsia (PI-FD), are limited. We conducted a systematic review and meta-analysis to determine prevalence of PI-IBS or PI-FD after acute gastroenteritis. DESIGN: We included observational studies recruiting ≥50 adults and reporting prevalence of IBS or FD after acute gastroenteritis with ≥3-month follow-up. A random effects model was used to estimate prevalence and ORs with 95% CIs. RESULTS: In total, 47 studies (28 170 subjects) were eligible. Overall prevalence of PI-IBS and PI-FD were 14.5% and 12.7%, respectively. IBS persisted in 39.8% of subjects in the long-term (>5 years follow-up) after diagnosis. Individuals experiencing acute gastroenteritis had a significantly higher odds of IBS (OR 4.3) and FD (OR 3.0) than non-exposed controls. PI-IBS was most associated with parasites (prevalence 30.1%), but in only two studies, followed by bacteria (18.3%) and viruses (10.7%). In available studies, Campylobacter was associated with the highest PI-IBS prevalence (20.7%) whereas Proteobacteria and SARS-CoV-2 yielded the highest odds for PI-IBS (both OR 5.4). Prevalence of PI-FD was 10.0% for SARS-CoV-2 and 13.6% for bacteria (Enterobacteriaceae 19.4%). CONCLUSION: In a large systematic review and meta-analysis, 14.5% of individuals experiencing acute gastroenteritis developed PI-IBS and 12.7% PI-FD, with greater than fourfold increased odds for IBS and threefold for FD. Proinflammatory microbes, including Proteobacteria and subcategories, and SARS-CoV-2, may be associated with the development of PI-IBS and PI-FD.

Alterations in gastrointestinal motility assessed by high-resolution antroduodenal manometry in patients with severe disorders of gut-brain interaction.

Data are limited regarding gastrointestinal motility disturbance in disorders of gut-brain interaction (DGBI). This study aimed to characterize antroduodenal motor alterations in patients with high-resolution antroduodenal manometry (HR-ADM). HR-ADM was performed in patients with severe DGBI and compared with healthy volunteers (HV). HR-ADM used a commercially available probe composed of 36 electronic sensors spaced 1 cm apart and positioned across the pylorus. Antral and duodenal motor high-resolution profiles were analyzed, based on the frequency, amplitude, and contractile integral/sensor (CI/s) calculated for each phase of the migrating motor complex (MMC). Eighteen HV and 64 patients were investigated, 10 with irritable bowel syndrome (IBS), 24 with functional dyspepsia (FD), 15 with overlap IBS-FD, and 15 with other DGBI. Compared with HV, patients had a lower frequency of phase II duodenal contractions (27 vs. 51 per hour; P = 0.002) and a lower duodenal phase II contraction amplitude (70 vs. 100 mmHg; P = 0.01), resulting in a lower CI/s of phase II (833 vs. 1,901 mmHg·cm·s; P < 0.001) in the duodenum. In addition, the frequency of phase II propagated antroduodenal contractions was lower (5 vs. 11 per hour; P < 0.001) in patients compared with HV. Interestingly, the antral CI/s of phase III was decreased in FD patients but not in IBS patients. Patients with severe DGBI display alterations in antral and intestinal motility assessed by commercially available HR-ADM. Whether these alterations may explain symptom profiles in such patients remains to be confirmed (NCT04918329 and NCT01519180).NEW & NOTEWORTHY Gastrointestinal dysmotility has been assessed poorly in disorders of gut-brain interaction (DGBI), especially with high-resolution antroduodenal manometry. Plots of DGBI patients showed lower duodenal contractions during phase II regarding amplitude, frequency, and contractile integral/sensor (CI/s) compared with healthy volunteers. A lower frequency of propagated antroduodenal contractions was also reported. Finally, antral CI/s was lower in patients with functional dyspepsia during phase III. Further studies are needed to assess the clinical significance of these alterations.

Impact of a pharmaceutical algorithm on patients with upper-gastrointestinal symptoms: A pre-post intervention study.

OBJECTIVE: To evaluate the algorithm impact on the upper gastrointestinal patients' symptoms (PROMs) and satisfaction with pharmaceutical care received (PREMs). METHODS: The algorithm was previously developed by clinicians and pharmacists, through a pre-post intervention study in Spain (June-October 2022). We included 1221 patients who were seeking advice and/or medication for symptoms at 134 community pharmacies. Patients' sociodemographic and clinical variables were assessed at baseline and were classified in accordance with the Gastroesophageal Reflux Disease Impact Scale (GIS) into patients with either epigastric, retrosternal or overlapping symptoms. Interventions included medical referral; education on healthy habits; prescription of an OTC treatment or a non-pharmacologic prescription. Fourteen days later, patients were assessed through: a) the change on the GIS score, and b) patients' satisfaction with pharmaceutical care received. RESULTS: Most patients reported overlapping symptoms (660, 54.0%), 171 (14.0%) reported epigastric symptoms and 390 (32.0%) retrosternal symptoms. Patients with epigastric symptoms did not show a difference in the GIS score after the intervention while those with retrosternal symptoms and those with overlapping symptoms did (mean 1.09 (4.28 SD), p < 0.001 and mean 3.18 (6.01 SD), p < 0.001, respectively). Patients who received education on healthy habits and those with a prescription of a pharmacological treatment (antiacids in monotherapy and alginates-antiacids) showed an increase in the GIS score. Patients' satisfaction with pharmaceutical care received was over 99.2% of sample. CONCLUSION: Implementation of the upper-gastrointestinal symptoms algorithm in Community pharmacies had a positive impact on patients' symptoms, quality of life, and satisfaction with pharmaceutical care received.

The effect of mindfulness-based cognitive therapy on the Clinical efficacy and psychological state in patients with functional dyspepsia.

BACKGROUND AND AIM: To observe the clinical therapeutic effect and mental state of mindfulness-based cognitive therapy (MBCT) in patients with functional dyspepsia (FD). METHODS: In this study, 80 patients suffering from FD in an outpatient clinic were enrolled from January to December 2020. Patients were randomly allocated into the control group (conventional treatment) and observation group (MBCT treatment). Patients in the control group were prescribed rabeprazole and mosapiride, and patients in the observation group were given MBCT therapy in addition to the above drugs. After treatment for 8 weeks, the changes in gastrointestinal symptom scores, anxiety, depression, mindfulness and sleep quality and gastric emptying testing were compared between these two groups. RESULTS: The observation group showed strikingly lower gastrointestinal symptom scores, SAS, SDS, PSQI, and SCL-90 scale scores, and higher FFMQ scale scores than the control group (p < 0.05). There was no conspicuous change in gastric emptying monitoring (p > 0.05). CONCLUSIONS: MBCT therapy can improve patients' gastrointestinal symptoms, attenuate their anxiety and depression levels, and ameliorate their sleep quality.

Improvement of functional dyspepsia with Suaeda salsa (L.) Pall via regulating brain-gut peptide and gut microbiota structure.

PURPOSE: The traditional Chinese herbal medicine Suaeda salsa (L.) Pall (S. salsa) with a digesting food effect was taken as the research object, and its chemical composition and action mechanism were explored. METHODS: The chemical constituents of S. salsa were isolated and purified by column chromatography, and their structures were characterized by nuclear magnetic resonance. The food accumulation model in mice was established, and the changes of the aqueous extract of S. salsa in gastric emptying and intestinal propulsion rate, colonic tissue lesions, serum brain-gut peptide hormone, colonic tissue protein expression, and gut microbiota structure were compared. RESULTS: Ten compounds were isolated from S. salsa named as naringenin (1), hesperetin (2), baicalein (3), luteolin (4), isorhamnetin (5), taxifolin (6), isorhamnetin-3-O-ß-D-glucoside (7), luteolin-3'-D-glucuronide (8), luteolin-7-O-ß-D-glucuronide (9), and quercetin-3-O-ß-D-glucuronide (10), respectively. The aqueous extract of S. salsa can improve the pathological changes of the mice colon and intestinal peristalsis by increasing the rate of gastric emptying and intestinal propulsion. By adjusting the levels of 5-HT, CCK, NT, SS, VIP, GT-17, CHE, MTL, and ghrelin, it can upregulate the levels of c-kit, SCF, and GHRL protein, and restore the imbalanced structure of gut microbiota, further achieve the purpose of treating the syndrome of indigestion. The effect is better with the increase of dose. CONCLUSION: S. salsa has a certain therapeutic effect on mice with the syndrome of indigestion. From the perspective of "brain-gut-gut microbiota", the mechanism of digestion and accumulation of S. salsa was discussed for the first time, which provided an experimental basis for further exploring the material basis of S. salsa.

Outcomes of pediatric endoscopic ultrasound-guided celiac plexus block: A single center pilot study.

Celiac plexus blocks (CPBs) using endoscopic ultrasound (EUS) guidance provide significant pain relief in adults with chronic pancreatitis. We present on EUS-guided CPB for pediatric patients with abdominal pain from chronic pancreatitis or severe functional dyspepsia necessitating clinically assisted nutrition and hydration. Patients who underwent EUS-CPB were included and followed prospectively at 2-, 4-, and 8-weeks postprocedure about pain, enteral tolerance, and school/activity attendance. Thirteen patients underwent EUS-guided CPB with a total of 21 procedures. In the pancreatitis cohort, mean pain relief was 11.7 weeks for those who responded. In the functional dyspepsia cohort, mean improvement (in either pain or enteral tolerance) was 4.8 weeks. Symptom improvement varied between the two cohorts. Acute recurrent/chronic pancreatitis patients demonstrated more sustained relief than the functional dyspepsia cohort. This study adds to the limited data investigating the utility of EUS-CPB as part of a multimodal treatment plan in pediatrics.

Metabolomic comparison of postprandial distress syndrome patients with and without duodenal eosinophilia.

OBJECTIVE: In functional dyspepsia patients, duodenal mucosal eosinophilia has been associated with early satiety but is not present in all patients suggesting varied pathways to symptom generation. The objective of the current study was to explore metabolic differences comparing those with duodenal mucosal eosinophilia to those without eosinophilia. METHODS: This study was conducted utilizing an existing biorepository. Patients had plasma samples obtained at the time of endoscopy. All had undergone endoscopy for dyspepsia and reported early satiety. Two groups were identified including those with peak duodenal mucosal eosinophil densities above 30/high power field (N = 28) and those below 30 (N = 16). The fasting plasma samples were analyzed by liquid chromatography/high-resolution mass spectrometry. Significant differences between groups were determined. RESULTS: The eosinophilia group demonstrated significant elevations in several gamma-glutamyl amino acids. The eosinophilia group had elevations of metabolites associated with oxidative stress including glutathione metabolites (cysteinlyglycine and cys-gly oxidized), and metabolites related to nitric oxide synthesis (arginine, citrulline, ornithine, and dimethylarginine). Eosinophilia was also associated with alterations in lipid metabolism including several long-chain acylcarnitine conjugated fatty acids. Carnitine levels were lower in the eosinophilia group. Lastly, vanillymandelate, a derivative of norepinephrine and epinephrine was elevated in the eosinophilia group. CONCLUSIONS: In patients with dyspepsia and early satiety, duodenal mucosal eosinophilia is associated with metabolites levels which are consistent with increased oxidative stress and alterations in lipid metabolism. Eosinophilia was also associated with lower carnitine levels. These alterations may contribute to pathophysiology and represent therapeutic targets.

A multicenter registry study on percutaneous electrical nerve field stimulation for pediatric disorders of gut-brain interaction.

OBJECTIVES: Percutaneous electrical nerve field stimulation (PENFS) has demonstrated promise in single-center trials for pediatric abdominal pain-related disorders of gut-brain interaction (DGBI). Our aim was to explore efficacy of PENFS as standard therapy for DGBI in a registry involving multiple pediatric gastroenterology referral centers. METHODS: This was a multicenter, prospective open-label registry of children (8-18 years) undergoing PENFS for DGBI at seven tertiary care gastroenterology clinics. DGBI subtypes were classified by Rome IV criteria. Parents and patients completed Abdominal Pain Index (API), Nausea Severity Scale (NSS), and Functional Disability Inventory (FDI) questionnaires before, during therapy and at follow-up visits up to 1 year later. RESULTS: A total of 292 subjects were included. Majority (74%) were female with median (interquartile range [IQR]) age 16.3 (14.0, 17.7) years. Most (68%) met criteria for functional dyspepsia and 61% had failed ≥4 pharmacologic therapies. API, NSS, and FDI scores showed significant declines within 3 weeks of therapy, persisting long-term in a subset. Baseline (n = 288) median (IQR) child-reported API scores decreased from 2.68 (1.84, 3.58) to 1.99 (1.13, 3.27) at 3 weeks (p < 0.001) and 1.81 (0.85, 3.20) at 3 months (n = 75; p < 0.001). NSS scores similarly improved from baseline, persisting at three (n = 74; p < 0.001) and 6 months later (n = 55; p < 0.001). FDI scores displayed similar reductions at 3 months (n = 76; p = 0.01) but not beyond. Parent-reported scores were consistent with child reports. CONCLUSIONS: This large, comprehensive, multicenter registry highlights efficacy of PENFS for gastrointestinal symptoms and functionality for pediatric DGBI.

Meal related symptoms in youth with chronic abdominal pain: Relationship to anxiety, depression, and sleep dysfunction.

OBJECTIVE: The objective of the current study was to describe meal-related symptoms in youth with chronic abdominal pain fulfilling criteria for a disorder of gut-brain interaction (DGBI) and their associations with anxiety, depression, and sleep disturbances. METHODS: This was a retrospective evaluation of 226 consecutive patients diagnosed with an abdominal pain-associated DGBI. As part of routine care, all had completed a standardized symptom history, the Sleep Disturbances Scale for Children (utilized to assess for disorders of initiation and maintenance of sleep and excessive daytime somnolence) and the Behavior Assessment System for Children-Third Edition (utilized to assess for anxiety and depression). Four meal related symptoms were assessed: early satiety, postprandial bloating, postprandial abdominal pain, and postprandial nausea. RESULTS: Overall, 87.6% of patients reported at least one meal related symptom and the majority reported at least three symptoms. All meal related symptoms were significantly related to each other. Postprandial pain and nausea were more often reported by females. Early satiety, postprandial bloating, and postprandial nausea, but not postprandial pain demonstrated significant though variable associations with anxiety, depression, disorders of initiation and maintenance of sleep, and disorders of excessive somnolence, but only in adolescents. CONCLUSIONS: Meal related symptoms are very common in youth with abdominal pain-associated DGBIs. Early satiety, bloating, and postprandial nausea demonstrate variable associations with anxiety, depression, and disordered sleep while increased postprandial pain was not associated with psychologic or sleep dysfunction, suggesting a different pathway for symptom generation.

Predicting acupuncture efficacy for functional dyspepsia based on functional brain network features: a machine learning study.

Acupuncture is effective in treating functional dyspepsia (FD), while its efficacy varies significantly from different patients. Predicting the responsiveness of different patients to acupuncture treatment based on the objective biomarkers would assist physicians to identify the candidates for acupuncture therapy. One hundred FD patients were enrolled, and their clinical characteristics and functional brain MRI data were collected before and after treatment. Taking the pre-treatment functional brain network as features, we constructed the support vector machine models to predict the responsiveness of FD patients to acupuncture treatment. These features contributing critically to the accurate prediction were identified, and the longitudinal analyses of these features were performed on acupuncture responders and non-responders. Results demonstrated that prediction models achieved an accuracy of 0.76 ± 0.03 in predicting acupuncture responders and non-responders, and a R2 of 0.24 ± 0.02 in predicting dyspeptic symptoms relief. Thirty-eight functional brain network features associated with the orbitofrontal cortex, caudate, hippocampus, and anterior insula were identified as the critical predictive features. Changes in these predictive features were more pronounced in responders than in non-responders. In conclusion, this study provided a promising approach to predicting acupuncture efficacy for FD patients and is expected to facilitate the optimization of personalized acupuncture treatment plans for FD.

Efficacy and Safety of STW 5-II for Functional Dyspepsia Treatment: A Patient Data-Based Meta-Analysis.

INTRODUCTION: Functional dyspepsia (FD) is a chronic relapsing gastroduodenal disorder with limited treatment options. Herbal products, like the six-herb combination STW 5-II, can target multiple FD gastrointestinal symptoms. In this meta-analysis, we evaluated the efficacy and safety of STW 5-II for overall FD, and key symptoms, based on Rome IV criteria. METHODS: We systematically screened the literature for randomized controlled clinical studies testing STW 5-II in FD. Meta-analysis was performed using data from individual patients with at least one key FD symptom (fullness, early satiety, or epigastric pain) of at least moderate severity at baseline. ANCOVA-based meta-analyses were performed on improvements in the total symptom sum score, and single symptoms, after 4 and 8 weeks. Safety data were analyzed by calculating odds ratios for all adverse events. RESULTS: Four randomized controlled trials, including 613 patients, were identified, and two were eligible for efficacy analysis. STW 5-II significantly improved the FD symptom sum score (mean difference of 1.74 after 4 weeks and 2.07 after 8 weeks) and key FD symptoms of fullness (0.28 and 0.29), early satiety (0.25 and 0.26), and epigastric/upper abdominal pain (0.26 and 0.3). Treatment-related or severe adverse events did not differ between STW 5-II and placebo. CONCLUSION: The results support that STW 5-II significantly improves FD symptoms after 4 and 8 weeks of treatment with no difference in relation to safety signals compared to placebo. Thus, STW 5-II can be considered an effective and safe treatment option for FD.

Low Vitamin D Levels in Patients with Symptoms of Gastroparesis: Relationships with Nausea and Vomiting, Gastric Emptying and Gastric Myoelectrical Activity.

Patients with gastroparesis (Gp) often have diets deficient in calories, electrolytes, and vitamins. Vitamin D levels have been reported to be low in some patients with Gp but has not been systematically studied. AIMS: To determine vitamin D levels and relationships among symptoms, gastric emptying and gastric myoelectrical activity (GMA) in patients with symptoms of Gp. METHODS: 25-hydroxy-vitamin D was measured in patients at enrollment in the Gastroparesis Clinical Consortium Registry. Gastroparesis Cardinal Symptoms Index (GCSI), gastric emptying, and GMA before and after water load satiety test (WLST) were measured. GMA, expressed as percentage distribution of activity in normal and dysrhythmic ranges, was recorded using electrogastrography. RESULTS: Overall, vitamin D levels were low (< 30 ng/ml) in 288 of 513 (56.1%) patients with symptoms of Gp (206 of 376 (54.8%) patients with delayed gastric emptying (Gp) and 82 of 137 (59.9%) patients with symptoms of Gp and normal gastric emptying). Low vitamin D levels were associated with increased nausea and vomiting (P < 0.0001), but not with fullness or bloating subscores. Low vitamin D levels in patients with Gp were associated with greater meal retention at four hours (36% retention) compared with Gp patients with normal vitamin D levels (31% retention; P = 0.05). Low vitamin D in patients with normal gastric emptying was associated with decreased normal 3 cpm GMA before (P = 0.001) and increased tachygastria after WLST (P = 0.01). CONCLUSIONS: Low vitamin D levels are present in half the patients with symptoms of gastroparesis and are associated with nausea and vomiting and gastric neuromuscular dysfunction.

Abnormal functional connectivity of the reward circuit associated with early satiety in patients with postprandial distress syndrome.

Postprandial distress syndrome (PDS) is the most common functional dyspepsia (FD) subtype. Early satiety is one of the cardinal symptoms of the PDS subtype in FD patients. The heterogeneity of symptoms in FD patients hampered therapy for patients based on specific symptoms, necessitating a symptom-based understanding of the pathophysiology of FD. To investigate the correlation between reward circuit and symptom severity of PDS patients, seed (Nucleus accumbens, NAc, a key node in the reward circuit) based resting-state functional connectivity (FC) was applied in the neuroimaging data analysis. The results demonstrated that the patients with PDS manifested strengthened FC between NAc and the caudate, putamen, pallidum, amygdala, hippocampus, thalamus, anterior cingulate cortex (ACC), and insula. Moreover, the FC between NAc and ACC, insula, thalamus, and hippocampus exhibited significant positive associations with symptom severity. More importantly, the strengthened FC between NAc and the ACC, insula, amygdala, and hippocampus were found associated with the early satiety symptom of patients with PDS. This study indicated that the altered FC of reward circuit regions may play a role in the pathophysiology of patients with PDS, and some of the aberrant NAc-based FC within the reward circuit were more related to the early satiety of patients with PDS. These findings improve our symptom-based understanding of the central pathophysiology of FD, lay the groundwork for an objective diagnosis of FD, and shed light on the precise prescription for treating FD based on symptoms.

Uncovering the material basis and mechanism of Jianwei Xiaoshi tablet against functional dyspepsia using ultra-high-performance liquid chromatography-mass spectrometry and network pharmacology.

Functional dyspepsia (FD) is a common digestive disease. Jianwei Xiaoshi (JWXS) tablet is composed of Radix Pseudostellariae (TZS), Pericarpium Citri Reticulatae (CP), Rhizoma Dioscoreae (SY), fired Hordei Fructus Germinatus (CMY) and Crataegi Fructus (SZ). It is a commonly used drug in the treatment of FD in China and has good therapeutic effects. However, there is very little research about the substance basis and action mechanism of JWXS tablet. In this research, ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS) and network pharmacology were used to explore the substance basis and action mechanism of the JWXS tablet. Finally, 19, 79, 22, 22 and 39 constituents were identified in the extracts of TZS, CP, SY, CMY and SZ, respectively. Based on these findings, a total of 104 ingredients were identified in JWXS tablet and 29 potentially absorbed ingredients were detected in rat plasma. The results of network pharmacology indicated that the inhibition of gastric acid secretion, the regulation of gastrointestinal motility, inflammation and immune response were the key approaches for treating FD with JWXS tablet. The material basis and potential action mechanism of JWXS tablet in treating FD were comprehensively clarified for the first time. This study will improve our understanding of JWXS tablet.

The prevalence of functional dyspepsia using Rome IV questionnaire among chronic kidney disease patients.

Background: Symptoms of dyspepsia are usually encountered by chronic kidney disease patients. Abdominal discomfort is commonly seen in CKD patients with no other causes of organic affection. Aim: to determine the prevalence of functional dyspepsia in CKD patients, and which subtype is predominant in them. Materials and patients: This observational study included 150 CKD patients. Clinical and laboratory data were recorded for every patient. All the patients were interviewed using the ROME IV questionnaire of functional dyspepsia. Patients fulfilling criteria for functional dyspepsia were exposed to upper GI endoscopy. Results: Overall, 73 (48.7%) of CKD patients were males and 77 (51.3%) were females with mean age of (45.71 ± 9.59) and mean BMI (26.58 ± 5.39). The frequency of functional dyspepsia among CKD patients was determined to be 14.7% (22 out of 150 patients). Among those affected by functional dyspepsia, the most prevalent subtype was found to be Epigastric Pain Syndrome (EPS), accounting for 59% (13 out of 22 cases). The most common predictor of FD in CKD patients was chronic HCV infection, hemodialysis, stage of CKD and eGFR as revealed by Univariate regression analysis. Conclusion: The prevalence of FD amongst CKD patients is 14.7% with EPS the predominant subtype. Male patients, HCV patients, patients with higher CKD stages and highly impaired eGFR (low eGFR) are more probable to have FD.

Efficacy of jing Si herbal tea in functional dyspepsia: A double-blind, randomized, placebo-controlled study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.