Neurogastroenterology and Motility最新文献

Background and aims: The endocannabinoid (eCB) system includes ligands (anandamide and 2-arachidonoyl glycerol, 2-AG), receptors and catabolizing enzymes (fatty acid amide hydrolase, FAAH and monoacylglycerol lipase) expressed in both the brain and gut. We investigated whether the FAAH inhibitor, URB597, influenced visceral pain to colorectal distension (CRD) in an acute stress-related model of visceral hypersensitivity induced by the selective corticotropin-releasing factor receptor subtype 1 (CRF₁) agonist, cortagine.

Methods: Male Sprague-Dawley rats were injected subcutaneously (SC) with URB597 (3 mg/kg) or vehicle and 2 h later, intraperitoneally with cortagine (10 μg/kg) or vehicle. The visceromotor responses (VMR) were assessed to a first CRD (baseline) before injections, and to a second CRD 15 min after the last treatment. Brain, jejunum, and proximal colon were collected from treated and naïve rats for levels quantification of three fatty acid amides (FAAs) [anandamide (arachidonyl-ethanolamide, AEA), oleoyl-ethanolamide (OEA) and palmitoyl-ethanolamide (PEA)], and 2-AG. In separate animals, defecation/diarrhea were monitored after URB597 and cortagine.

Key results: URB597 inhibited cortagine-induced increased VMR at 40 mmHg (89.0 ± 14.8% vs. 132.5 ± 15.6% for vehicle SC, p < 0.05) and 60 mmHg (107.5 ± 16.1% vs. 176.9 ± 24.4% for vehicle SC, p < 0.001) while not influencing basal VMR. In URB597 plus cortagine group, FAAs levels increased in the brain and intestinal tissue while 2-AG did not change. URB597 did not modify cortagine-induced defecation/diarrhea versus vehicle.

Conclusions and inferences: URB597 shows efficacy to elevate brain and intestinal FAAs and to counteract the colonic hypersensitivity induced by peripheral activation of CRF₁ signaling supporting a potential strategy of FAAH inhibitors to alleviate stress-related visceral hypersensitivity.

Background: Opioids inhibit motility and secretion of the gut and have been used for antidiarrheal treatment for centuries. However, the underlying mechanisms of opium tincture are not evident.

Aim: To investigate the effects of opium tincture on gastrointestinal motility, intestinal volumes, and water content of different gut segments assessed by magnetic resonance imaging (MRI).

Methods: Twenty healthy volunteers were included in a randomized, placebo-controlled, crossover study of 9 days of treatment with 30 drops of opium tincture per day. MRI was performed on day 1 (before treatment) and day 9 (during treatment). Measurements included assessments of gastric volume, gastric emptying, gastric motility, small bowel volume, small bowel water content, small bowel motility, colon volume, colon water content, and whole gut transit.

Key results: Opium tincture delayed gastric emptying by a mean difference of 5.6 min [95% CI: 1.8-9.4], p = 0.004, and increased postprandial gastric meal volume (17-21%, p = 0.02). Small bowel endpoints did not change. Opium tincture delayed whole gut transit time (p = 0.027) and increased ascending colon volume by 59 mL [95% CI: 15-103], p = 0.004, and transverse colon volume by 48 mL [95% CI: 4-92], p = 0.027. T1-relaxation time of the descending colon chyme was decreased during opium treatment, indicating dryer feces (difference: -173 ms [95% CI: -336 -11], p = 0.03).

Conclusion and inferences: Opium tincture induced changes in the stomach and colon in healthy volunteers. An improved understanding of how opioids affect gut functions may lead to a better understanding and optimized management of diarrhea.

Background: Disorders of primary peristalsis are associated with a higher percent time pH <4 in the esophagus suggesting poor acid clearance. However, there are no studies of secondary peristalsis and its relationship to microscopic or erosive esophagitis. The goal of this study was to determine the relationship between secondary peristalsis using functional luminal imaging probes (EndoFLIP) and the presence or absence of esophagitis.

Methods: We reviewed the endoscopic and EndoFLIP 2.0 tracings for 103 consecutive patients including those with a history of upper gastrointestinal surgery undergoing upper endoscopy. Esophagogastric junction (EGJ) distensibility and diameter, repetitive antegrade contraction (RACs) presence and frequency, and occlusive diameters were measured. Measurements were then compared between patients with and without microscopic and/or erosive esophagitis. Means were compared using t-tests. Proportions were compared using Chi-Squared analyses.

Key results: One hundred and three patients were included (mean age: 14.4 + 6.4 years). Ten patients had erosive esophagitis and 28 patients had microscopic esophagitis. Erosive and microscopic esophagitis were associated with abnormal or absent of RACs (p < 0.001). Occlusive diameters were higher in patients with esophagitis compared to those without (p < 0.001). There was no relationship between EGJ distensibility and the presence of erosive or microscopic esophagitis (p = 0.4). The absence of RACs was the only independent predictor of esophagitis (erosive and microscopic), after controlling for age, proton pump inhibitors (PPI) use and EGJ distensibility (p < 0.001).

Conclusions & inferences: Abnormal secondary peristalsis is associated with microscopic and gross esophagitis, suggesting that EndoFLIP should be part of the diagnostic algorithm for esophagitis.

Background: Unsupervised machine learning describes a collection of powerful techniques that seek to identify hidden patterns in unlabeled data. These techniques can be broadly categorized into dimension reduction, which transforms and combines the original set of measurements to simplify data, and cluster analysis, which seeks to group subjects based on some measure of similarity. Unsupervised machine learning can be used to explore alternative subtyping of disorders of gut-brain interaction (DGBI) compared to the existing gastrointestinal symptom-based definitions of Rome IV.

Purpose: This present review aims to familiarize the reader with fundamental concepts of unsupervised machine learning using accessible definitions and provide a critical summary of their application to the evaluation of DGBI subtyping. By considering the overlap between Rome IV clinical definitions and identified clusters, along with clinical and physiological insights, this paper speculates on the possible implications for DGBI. Also considered are algorithmic developments in the unsupervised machine learning community that may help leverage increasingly available omics data to explore biologically informed definitions. Unsupervised machine learning challenges the modern subtyping of DGBI and, with the necessary clinical validation, has the potential to enhance future iterations of the Rome criteria to identify more homogeneous, diagnosable, and treatable patient populations.

Background: High-resolution Manometry (HRM) is the most sensitive and specific test available for clinical assessment of hiatal hernia (HH), a common condition defined as the separation between the Lower Esophageal Sphincter (LES) and crural diaphragm (CD). While the link between HH and Gastroesophageal Reflux Disease (GERD) is established, the potential association of HH with esophageal dysmotility, independently from GERD, is uncertain. This study aimed to analyze if HH, with or without GERD, can associate with esophageal motility disorders.

Methods: Consecutive patients without previous esophageal surgery who underwent HRM between 2018 and 2022 were enrolled. All patients with symptoms suggestive of GERD underwent impedance-pH testing off-therapy. HH was defined as a separation >1 cm between LES and CD, and esophagogastric junction (EGJ) morphology was classified as: Type I, when there was no separation between LES and CD; Type II, in case of minimal separation (>1 and <3 cm); Type III, when ≥3 cm of separation was present. Demographic and clinical characteristics were collected at baseline, including Age, Gender, Alcohol-, Coffee- and Smoke-habits, GERD diagnosis and symptoms' duration. Two cohorts of patients, with and without HH, were retrospectively individuated, and their association with Ineffective Peristalsis, Hypercontractile Esophagus and Outflow Obstruction was analyzed with univariate and multivariate Logistic regressions using the statistical software R.

Key results: 848 consecutive patients were enrolled, and 295 cases of HH (34.8%), subdivided into 199 (23.5%) Type II- and 96 (11.3%) Type III-EGJ patients, were identified. Ineffective peristalsis was diagnosed in 162 (19.1%) subjects, Hypercontractile esophagus in 32 (3.8%), and Outflow Obstruction in 91 (10.7%), while GERD was present in 375 (44.2%) patients. HH was significantly associated with Ineffective Peristalsis (p < 0.001) and GERD (p < 0.001). Furthermore, HH resulted to be a risk factor for Ineffective peristalsis (OR 2.0, 95% CI 1.4-2.8, p < 0.001) both when the analysis was conducted in all the 848 subjects, independently from GERD, and when it was carried out in patients without GERD (OR 2.3, 95% CI 1.02-5.3, p = 0.04). The risk for Ineffective Peristalsis increased 1.3 times for every centimeter of HH. No statistically significant association was found between HH and Outflow obstruction or Hypercontractile Esophagus.

Conclusions & inferences: An increasing separation between the LES and CD may lead to a gradual and significant elevation in the risk of Ineffective Peristalsis. Interestingly, this association with HH is true in patients with and in those without GERD, suggesting that the anatomical alteration seems to play a major role in motility change.

Background: Esophageal motility disorders are mainly evaluated with high-resolution manometry (HRM) which is a time-consuming and uncomfortable procedure with potential adverse events. Acoustic characterization of the swallowing has the potential to be an alternative noninvasive procedure.

Methods: We compared the findings on HRM and swallowing sounds in 43 patients who were referred for evaluation of dysphagia. The sound analysis was done with empirical mode decomposition method and with artificial intelligence (AI) and the estimated integrated relaxation pressure (IRP) from a two-layer neural network method was compared to measured IRP on HRM. The model then was tested in five patients.

Key results: IRP was estimated with high accuracy using the model developed with two-layer neural network method.

Conclusions & inferences: The analysis of acoustic properties of swallowing has the potential to be used for evaluation of esophageal motility disorders, this needs to be further evaluated in larger studies.

Background: There is a large unmet need for alternative, non-invasive, and accurate diagnosis of small intestinal bacterial overgrowth (SIBO). The smart capsule bacterial detection system (SCBDS) device contains a targeted sampling technology and an onboard SCBDS assay to detect metabolically active bacteria in the small intestine. Here, we evaluated the agreement of SCBDS assay with duodenal aspiration/culture ex vivo in a multicenter clinical study.

Methods: Duodenal aspiration was performed in subjects with gastrointestinal symptoms suggestive of SIBO. Aspirated fluid was sent to local and central microbiology labs to evaluate the agreement for detecting bacteria with SCBDS assay compared to the total bacterial count (TBC) reference standard. The performance of SCBDS assay was evaluated using a receiver operator curve, sensitivities, and specificities.

Key results: Aspirates from 66 patients were collected and analyzed for TBC and SCDBS assay. The overall agreement between the two assays was 82%-92% across 3 clinical sites. The SCBDS assay had a sensitivity of 67%-100% and a specificity of 90%-97% using either ≥ 10³ or 10⁵ CFU mL^-1 cutoff. Additionally, there was a good correlation (r = 0.82) for the TBC culture between the local and central labs.

Conclusions and inferences: The SCBDS assay showed a high level of agreement with TBC and improved performance compared to other non-invasive tests. These results demonstrate the potential utility of SCBDS device to aid SIBO diagnosis as a simple and non-invasive tool that merits further clinical validation.

Background: The aims of this study were to confirm the non-inferiority of tegoprazan to lansoprazole up to week 4 in patients with erosive esophagitis (EE) and to evaluate its effectiveness in rapid mucosal healing and symptom relief at week 2.

Methods: In this multi-center, randomized, double-blind, active-comparator non-inferiority trial, 218 patients with endoscopically confirmed EE (Los Angeles Classification Grades A-D) were randomly allocated to either the tegoprazan (50 mg) or lansoprazole (30 mg) group. The primary endpoint was the cumulative proportion of patients with healed EE up to week 4, as confirmed through endoscopy. The proportion of patients with healed EE at week 2 was also evaluated. Furthermore, CYP2C19 genotypes, symptoms, safety, and tolerability were assessed.

Key results: In the full-analysis set, 103 and 109 participants in the tegoprazan and lansoprazole groups, respectively, were analyzed. The cumulative healing rates up to week 4 were 95.2% (98/103) and 86.2% (94/109) (difference [95% confidence interval], 8.91 [1.22-16.59]; p < 0.0001 for non-inferiority and 0.0266 for superiority), while those at week 2 were 88.4% (91/103) and 82.6% (90/109) (5.78 [-3.66-15.22], p = 0.0005 for non-inferiority) for tegoprazan and lansoprazole, respectively. Tegoprazan showed consistent healing rates regardless of CYP2C19 genotypes.

Conclusions and inferences: Tegoprazan was superior to lansoprazole in the treatment of EE up to 4 weeks. Further studies are necessary to confirm these findings and clarify the superiority of tegoprazan, especially in the treatment of severe EE.

Trial registration: ClinicalTrials.gov identifier: NCT05267743.

Background: Although different gastric shapes are encountered in gastric emptying scintigraphy (GES), it is not known whether gastric shape is related to gastric emptying (GE) or symptoms.

Aim: To investigate different stomach shapes observed during GES and examine their associations with GE, body weight, and gastrointestinal (GI) symptoms.

Methods: This was a retrospective review of GES studies performed at our institution. Patients with prior gastric surgery were excluded. A classification of gastric shapes included: crescentic, J-shaped, reversed-L, cylindrical, and bag-like. Gastric shapes were correlated with GE, BMI, and GI symptoms using PAGI-SYM.

Results: 397 GES studies were reviewed (317 females, age 40.0 ± 20.3 years, BMI 27.8 ± 13.8 kg/m²). Gastric shapes were: 41.8% crescentic/comma-shaped, 34.0% J-shaped, 19.9% reversed L-shape, 2.8% cylindrical, and 1.5% bag-like. BMI was highest in crescentic/comma-shaped stomachs (30.1 ± 12.4 kg/m²) and lowest in bag-like stomachs (25.2 ± 9.9 kg/m²; p = 0.022). Delayed GE was most pronounced in bag-like stomachs (34.4 ± 33.1% retention at 4 h) and lowest in reversed-L shape (10.3 ± 15.6% retention at 4 h; p = 0.008). Regurgitation severity was greatest in bag-like stomachs (2.2 ± 1.5) compared to milder symptoms in reversed-L shape (1.3 ± 1.4; p = 0.029). Heartburn severity was increased in bag-like stomachs (2.3 ± 1.6) while patients with cylindrical stomachs reported least heartburn severity (1.1 ± 1.3; p = 0.11).

Conclusions: A classification system based on five gastric shapes observed during GES showed that crescent-shaped stomach was the most common shape and correlated with higher BMIs. Delayed GE was most pronounced in bag-like stomachs and lowest in reversed-L stomachs. Regurgitation and heartburn severity were greatest in bag-like stomachs with milder symptoms in reversed-L stomachs. Thus, gastric shape during GES is associated with gastric emptying, BMI, and symptom severity.

Background: The knowledge and proficiency of primary care practitioners (PCPs) in diagnosing and managing irritable bowel syndrome (IBS) remain generally low and variable internationally. This variability is partly due to a lack of familiarity with the Rome Foundation diagnostic criteria and treatment guidelines for this condition.

Methods: We conducted an electronic survey of PCPs in the United States and nine European countries to assess their understanding of IBS pathophysiology; the use of Rome IV criteria in diagnosis, knowledge of and frequency in prescribing various recommended treatments; and the likelihood of referring patients with suspected IBS to subspecialists.

Results: Most PCPs in the United States and Europe perceive IBS as a diagnosis of exclusion rather than a definitive diagnosis. They also believe IBS is underdiagnosed in primary care and challenging to diagnose confidently. The majority of PCPs consider diet as a crucial component of IBS management. Notably, US PCPs reported greater confidence than their European counterparts in recommending dietary interventions such as increased dietary fiber, a low FODMAP diet, and gluten restriction. Conversely, both groups exhibited moderate to high confidence in recommending over-the-counter treatments. European PCPs showed greater confidence in treating IBS with antispasmodics and secretagogues, while US PCPs expressed greater confidence in prescribing neuromodulators. Additionally, US PCPs were more likely to refer patients with suspected IBS to a gastroenterologist, whereas both US and European PCPs showed similar referral patterns to dietitians and referred very few patients to mental health providers. Both US and European PCPs reported that IBS is moderately to extremely difficult to treat effectively and emphasized the importance of a strong and longitudinal doctor-patient relationship in managing the condition.

Conclusion: Despite the Rome Foundation recommendations and criteria to support a positive diagnosis of IBS, most PCPs still rely on exclusionary investigations such as endoscopy and a serologic workup, while a significant percentage suggest referring patients to gastroenterologists.