Neurogastroenterology and Motility最新文献

Background: Colorectal cancer (CRC) is a leading cause of cancer-related deaths, significantly disrupting enteric neurotransmission within the colon. While the effects of CRC on the enteric nervous system (ENS) of the colon are well documented, its impact on the small intestine remains underexplored. This study aims to investigate the influence of colorectal carcinogenesis on the small intestine's ENS and evaluate the individual neuroprotective effects of microencapsulated quercetin and Bifidobacterium animalis.

Methods: Wistar rats were subjected to chemically induced colorectal carcinogenesis, followed by 14 weeks of treatment with microencapsulated quercetin and B. animalis. Gastrointestinal transit times were assessed, and colonic and jejunal samples underwent histopathological and immunohistochemical analyses to evaluate neuronal markers (HuC/D, nNOS, VIP). Cholinergic neurons were not directly assessed.

Results: Aberrant crypt foci confirmed the effectiveness of the colorectal carcinogenesis induction model. The mean gastric emptying time (MGET) was notably shorter in the B. animalis-treated group. Colorectal carcinogenesis significantly reduced the density and size of HuC/D+ neurons in the myenteric and submucosal plexuses of the jejunum. Treatments with either microencapsulated quercetin or B. animalis significantly enhanced neuronal density and size in the jejunum and improved nitrergic neuronal density (nNOS-IR). Additionally, VIPergic neuron density increased in the submucosal plexus, and varicosity size increased in the myenteric plexus in the CR group; treatments reduced this varicosity size.

Conclusion: This study provides the first evidence that colorectal carcinogenesis damages jejunal neurons. Treatments with microencapsulated quercetin or B. animalis independently preserved neuronal density and modulated gastrointestinal function. However, their combined administration did not enhance these effects, highlighting the need for further research into therapeutic interventions for preserving ENS integrity during colorectal carcinogenesis.

Background: Current treatment options for irritable bowel syndrome (IBS) mainly focus on restoring abnormal stool patterns but are less effective in relieving abdominal pain. Recent studies have identified mast cells as key players in visceral hypersensitivity (VHS) via histamine acting on histamine 1 receptor (H1R) activation. Our previous multicenter clinical trial showed clinical improvement of non-constipated IBS patients during treatment with 20 mg of the H1R-antagonist ebastine. Based on urticaria clinical trials showing increased symptom control with increased antihistamine dosage, we compared the effect of ebastine 20 mg vs. 40 mg in an open label study.

Methods: The effect of treatment of non-constipated IBS patients with ebastine 20 mg (n = 92) or 40 mg (n = 73) for 12 weeks was compared. Abdominal pain was assessed at baseline and at week 12 using a 10-point Visual Analogue Scale. Abdominal pain responders were defined as patients with at least 30% decrease in score compared to baseline, substantial abdominal pain responders with at least 50% reduction. Common gastrointestinal symptoms were evaluated using the GSRS questionnaire.

Key results: The percentage of abdominal pain responders and substantial abdominal pain responders was significantly increased with ebastine 40 mg compared to 20 mg (62% vs. 32%; p = 0.0014 and 40% vs. 12%; p = 0.0010, respectively). Moreover, the severity of diarrhea was significantly reduced with ebastine 40 mg (-1.0 (2.0) vs. 0.4 (1.8); p = 0.0334).

Conclusions: Our study shows that ebastine 40 mg is more effective than 20 mg, resulting in increased symptom control, in particular reduction in abdominal pain, and supports further evaluation of ebastine as treatment of non-constipated IBS.

Background: Diabetic gastroenteropathy can cause significant diagnostic challenges. Still, it remains unknown if measures of extraintestinal autonomic function reflect diabetic gastroenteropathy. We aimed to assess the associations between (1) gastrointestinal symptoms and motility measures and (2) gastrointestinal symptoms/motility measures and extraintestinal autonomic markers.

Methods: We included 81 persons with type 1 or type 2 diabetes (65% female, mean age 54) with gastrointestinal symptoms and autonomic neuropathy. The Gastroparesis Cardinal Symptom Index (GCSI) and the Gastrointestinal Symptom Rating Scale (GSRS) assessed gastrointestinal symptoms. The wireless motility capsule (Smartpill™) assessed panenteric transit times and motility indices. Cardiovascular reflex tests (VAGUS™) and cardiac vagal tone (eMotion Faros) estimated cardiovascular autonomic neuropathy, while the SUDOSCAN™ evaluated sudomotor function.

Key results: Proximal gastrointestinal symptoms were positively associated with the gastric motility index (GCSI: 1.18 (1.04-1.35), p = 0.01; GSRS: 1.15 (1.03-1.29), p = 0.02; median ratio (95% CI)), while only satiety correlated with gastric emptying time (1.24 (1.03-1.49), p = 0.02). Diarrhea was associated with decreased small bowel transit time (0.93 (0.89-0.98), p = 0.005), while constipation were associated with prolonged colonic transit time (1.16 (1.03-1.31), p = 0.02). Gastrointestinal symptoms increased with the degree of abnormal cardiovascular reflex tests (GCSI: 0.67 (0.16-1.19), p = 0.03; GSRS: 0.87 (0.30-1.45), p = 0.01; mean difference (95% CI)) but not with motility measures. Cardiac vagal tone and sudomotor function were not associated with gastrointestinal markers.

Conclusions & inferences: Gastrointestinal and extraintestinal autonomic measures were not associated. However, proximal gastrointestinal symptoms were associated with the gastric motility index and cardiovascular reflex tests. Hence, the latter may contribute to evaluating whether proximal gastrointestinal symptoms are autonomically derived.

Introduction: Functional lumen imaging probe (FLIP) planimetry performed during peroral endoscopic myotomy (POEM) evaluates esophagogastric junction (EGJ) metrics. The 16 cm FLIP catheter allows for topographical assessment of the esophageal body, and previous intraoperative studies have only utilized the 8 cm catheter or combined data from both catheters. Our aim was to characterize the utility of the 16 cm catheter during POEM with respect to intraoperative tailoring of the myotomy length and intermediate outcomes after POEM.

Methods: We conducted a retrospective review of procedural and follow-up information of consecutive patients who underwent POEM with an intraoperative 16 cm catheter between January 2020 and September 2023.

Results: In 100 patients with intraoperative FLIP, the mean myotomy length was 8.2 cm. A tailored short myotomy (≤ 4 cm) using FLIP was performed in 10% of cases with comparable outcomes in LES obstruction and GERD metrics compared to > 4 cm myotomy length. On the basis of topographical FLIP findings, the myotomy was extended to capture spastic body features in 32% of cases including Type 2 achalasia (5), epiphrenic diverticulum (3) and prior myotomy (10). In intervention-naive patients, 70.5% achieved clinical success (Eckardt ≤ 3) at median follow-up of 30.9 months (IQR 6.5-40.9 months) with improvement in LES obstruction and GERD metrics among the intermediate follow-up cohort. An intraoperative post-myotomy EGJ diameter of ≥ 16 mm was associated with a lower rate of repeat intervention (2 vs. 5 patients, p = 0.038) and not associated with increased reflux outcomes.

Conclusion: Intraoperative FLIP using the 16 cm catheter during POEM enables a tailored myotomy guided by both EGJ metrics and topographical assessment.

Background: Functional dyspepsia (FD) and irritable bowel syndrome (IBS) are disorders of gut-brain interaction (DGBIs). Patients with these disorders experience abdominal symptoms, frequently in relation to meal intake, and often are treated using pharmacological approaches that offer limited symptom relief. In addition to various pharmacotherapies, established treatment options include lifestyle modifications (such as diet) and, in certain patients, psychological interventions. Because of the limitations of the currently available treatments, many patients look for alternative options, including herbal preparations.

Purpose: In this review, we summarize the preclinical and clinical evidence informing the use of the herbal preparation, STW 5-II, for the treatment of patients with FD and IBS. Data from clinical trials provide evidence that STW 5-II is superior to placebo in offering symptom relief. Moreover, a substantial body of preclinical data on the mechanisms of action of STW 5-II suggests that its ingredients target multiple mechanisms relevant to pathophysiology and symptom generation that may underlie its beneficial clinical effects in patients with DGBIs.

Background and aims: Gastroparesis and functional dyspepsia often share overlapping upper gastrointestinal symptoms but may differ in symptom patterns, treatment, and health care utilization. We assessed their clinical similarities and distinctions in the largest national cohort study to date.

Methods: We performed a retrospective cohort study using the TriNetX database, identifying patients through administrative codes. Individuals with structural gastric or small bowel abnormalities or prior gastric surgery were excluded. Gastroparesis required a diagnosis within three months of a gastric emptying study, at least one typical symptom, and an upper endoscopy within 12 months prior. Functional dyspepsia required a diagnosis with prior endoscopy (1-12 months) and symptoms 6-12 months before diagnosis. Primary outcomes were medication use and healthcare utilization; secondary outcomes included symptom burden and coexisting disorders of gut-brain interaction. Propensity score matching (1:1) adjusted for demographics and comorbidities. Relative risks with 95% confidence intervals were calculated.

Results: We identified 2488 patients with gastroparesis and 3676 with functional dyspepsia; after matching, 1914 per group remained. Gastroparesis showed greater use of prokinetics (52.7% vs. 19.6%; p < 0.0001) and antiemetics, and higher rates of endoscopy (41.4% vs. 21.2%), emergency visits (45.3% vs. 40.2%), and hospitalization (28.2% vs. 21.6%) (all p < 0.01). Nausea, vomiting, and distension were more frequent in gastroparesis, while epigastric pain predominated in functional dyspepsia (p < 0.0001).

Conclusion: Gastroparesis and functional dyspepsia show distinct symptom distributions and treatment patterns, with higher health care utilization in gastroparesis, supporting mechanism-based individualized management.

Background: The London classification (LC) standardizes the interpretation of anorectal manometry, but real-world data using high-definition three-dimensional anorectal manometry (3D HD-ARM) remain limited.

Objective: To characterize anorectal manometric patterns in a large 3D HD-ARM cohort applying the LC and to assess additional functional parameters not included in the classification.

Methods: We retrospectively analyzed 300 consecutive 3D HD-ARM studies with balloon expulsion testing (BET). Clinical subgroups were defined using validated questionnaires: St. Mark's score for anal incontinence (AI) and Knowles-Eccersley-Scott Symptom score for chronic constipation (CC).

Results: Anal incontinence (AI) was highly prevalent (81.7%), with 75.7% reporting moderate-to-severe fecal incontinence. CC was present in 56.7%, and 49.1% showed overlapping symptoms. The most frequent major finding was rectal hyposensitivity (43.3%) and anal normotension with hypocontractility (16.3%). Anal normotension with hypocontractility best correlated with AI [OR 14.5 (95% CI 1.9-110.2; p = 0.010)], while anal hypertension was more frequent in CC [OR 2.2 (95% CI 1.3-3.9; p = 0.005)]. Rectoanal coordination disorders were common, with inconclusive patterns in 54.4%, limiting diagnostic precision. Among constipated patients with obstructive defecation syndrome (ODS), pathological coordination was more frequent [OR 3.5 (95% CI 1.1-12.1; p = 0.040)]. Additional parameters not included in the LC-reduced functional anal canal length and shorter sustained squeeze duration-were more evident in women with AI, whereas ultraslow waves were associated with CC. Sphincter defects were detected in 13%, mainly in women and AI patients.

Conclusion: The LC enables consistent phenotyping of anorectal dysfunction, highlighting major abnormalities as highly prevalent. However, frequent minor and inconclusive findings-particularly in defecatory coordination-underscore limitations of the current classification and the need for refinement.

Background: Secretory heparan sulphate proteoglycans (HSPGs) interact with various morphogens, growth factors, and signaling molecules contributing to the development of the enteric nervous system (ENS). Thus, HSPGs have come into focus as pathomechanistic players of enteric neuropathies, such as Hirschsprung's disease (HSCR) in animal models. However, a detailed description of HSPG expression in human HSCR patients is missing.

Methods: We characterized the expression pattern of the secretory HSPGs perlecan, COL18A1, and agrin in the human ENS and investigated differences in affected and healthy intestinal segments. Thus, comparative immunostainings were performed on human gut samples from HSCR-patients and on non-HSCR controls as well as tissues from human body donors.

Key results: Strikingly, we found that perlecan, COL18A1, and agrin were expressed as periganglionic basement membrane-like structures in the human ENS. Interestingly, the expression pattern in normoganglionic and hypoganglionic HSCR-tissues was comparable to the expression pattern in control tissues, despite the loss of neuronal differentiation markers in hypoganglionic segments. In aganglionic segments, the immunoreactivity of the investigated secretory HSPGs in the intermuscular layer was markedly reduced or not detectable. Yet, they were still readily visible in the Tunica muscularis, around blood vessels, and in the epithelium, with an almost unaltered immunoreactive pattern compared to the ganglionic segment.

Conclusion: Our study transferred valuable findings on the role of HSPGs in ENS development gained in animal models to human HSCR patients. Beyond their implications for understanding enteric neuropathies, we discuss our findings in the context of how the extracellular matrix might regulate homeostasis and regeneration in the human ENS.

Background: The COVID-19 pandemic has unveiled a hidden epidemic of disorders of gut-brain interaction (DGBIs), notably post-infection irritable bowel syndrome (PI-IBS), driven by SARS-CoV-2 GI tropism and pandemic stressors.

Purpose: This review synthesizes and critically appraises current evidence on the prevalence, clinical spectrum, and predictors of post-COVID-19 IBS, integrating mechanistic insights. Topics discussed in this review will advance understanding of pathophysiological mechanisms, identify therapeutic targets, inform phenotype-tailored management and clinical care, and outline research priorities for post-COVID-19 IBS.

Methods: A narrative review was performed by the authors.

Key results: Recent evidence indicates that approximately 7.2% of individuals develop IBS after SARS-CoV-2 infection, with 2.6-fold higher odds vs. non-infected controls. At the population level, a nationally representative U.S. survey (> 160,000 adults) showed a pandemic-era surge in IBS prevalence (predominantly IBS-M) and a modest increase in chronic idiopathic constipation (CIC), while other Rome IV DGBIs remained stable. Mechanisms are multifactorial, involving ACE2-linked epithelial/neuromuscular effects, persistent low-grade inflammation, microbiota dysbiosis with reduced short-chain fatty acids, altered serotonin signaling, barrier dysfunction, and psychosocial stress acting along the gut-brain axis. Emerging data indicate dyspnea and depression further mediate the COVID-19-to-IBS pathway, underscoring biopsychosocial endotypes.

Conclusions and inferences: This review indicates that following infection with SARS-CoV-2, DGBI, particularly IBS, occurs in 7.2% patients on follow-up. Clinically, a positive diagnosis framework and phenotype-tailored, multidisciplinary care are recommended. Future studies on post-infection IBS including post-COVID-19 IBS should be undertaken using upcoming Rome V criteria, controlling for confounding factors, and defining mechanistic endotypes to unlock precision therapies.