Neurogastroenterology and Motility最新文献

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.

Objective: Intestinal ischemia-reperfusion injury (IIRI) is common in a variety of critical diseases and acute stress, and acupuncture is a promising treatment for IIRI. The aim of this study is to explore the mechanism of electroacupuncture (EA) at Zusanli (ST36) in improving IIRI from the perspective of the cholinergic anti-inflammatory pathway (CAP) and miRNA 124.

Methods: Seven groups of mice were performed: Control group, I/R group (IIRI model), EA group (I/R + EA), miRNA mimic group (I/R + EA + miRNA 124 mimic), miRNA inhibitor group (I/R + EA + miRNA 124 inhibitor), PNU group (I/R + EA + α7nAChR agonist), and MLA group (I/R + EA+ α7nAChR antagonist). The expression of intestinal macrophages, α7nAChR, miRNA 124, and related molecules, including p-STAT3 and IL-6, as well as histological damage (Chiu's score) and mucosal permeability (serum FD4 concentration), were detected.

Results: The serum FD4 concentrations in the EA and PNU groups were significantly lower compared to the I/R group (p < 0.05). The expression of intestinal α7nAChR and miRNA 124 in the EA, miRNA mimic, and PNU groups was higher than that in the I/R group (p < 0.05), while levels of p-STAT3 and IL-6 were reduced (p < 0.05). Conversely, in the miRNA inhibitor and MLA groups, miRNA 124 levels were significantly lower than in the EA group (p < 0.05), and IL-6 levels were increased (p < 0.05).

Conclusion: EA at Zusanli may induce miRNA124 through the cholinergic pathway on intestinal macrophages, which may be a key neuro-immune target of EA in the treatment of IIRI.

Background and aims: Supragastric belches (SGB) are not detected by commercial software and are cumbersome to identify manually. We determined whether machine learning can accurately identify SGBs.

Methods: pH-impedance studies from a convenience cohort (20 patients each of pathologic GERD, excessive SGB, and healthy volunteers) were randomly assigned to training (2), validation (4), and testing (4) from each group. First, studies were manually reviewed to mark SGBs, then converted to .csv files and input into a convolutional neural network (CNN) developed de novo using open-source software. The training set was utilized for hyperparameter and epoch optimization. Subsequently, clinical utility was assessed using a validation set followed by test set to confirm accuracy. False positives were reviewed, allowing recognition of novel CNN-detected events.

Results: 339 SGB events (median 8.0) were manually identified in the GERD cohort, > 2000 in the SGB cohort and 163 (median 3.0) in healthy volunteers. When analyzed by group, sensitivity was highest in healthy volunteers and lowest in the GERD cohort, while false positive rates were similar. Unique new SGB events were most common in the SGB cohort (p < 0.001 compared to the other cohorts). On ROC analysis, machine learning segregated SGB patients from GERD and healthy volunteers with high accuracy (AUC 0.859, p = 0.001) at an optimal threshold of 11 events, with sensitivity of 100% and specificity of 62.5%.

Conclusions: In this proof-of-concept investigation, a machine learning algorithm accurately identifies SGB events, including events missed by manual review, and reliably segregates SGB patients from healthy volunteers and GERD patients.

Background and aims: Alpha-gal syndrome (AGS) is an IgE-mediated hypersensitivity to galactose-α-1,3-galactose, triggered by tick bites. It typically presents with delayed onset allergic or gastrointestinal symptoms after red meat consumption. This study aims to evaluate the prevalence of clinical symptoms and outcomes in AGS patients.

Methods: A systematic search of PubMed, Embase, and Cochrane Central was conducted to identify studies with at least five AGS patients that utilized alpha-gal IgE for diagnosis and reported symptomatology. A random-effects model calculated pooled prevalence and 95% confidence intervals (CIs) for clinical characteristics of AGS.

Results: Of the 739 studies screened, 15 met the inclusion criteria, comprising 1162 AGS patients (57% female). Urticaria was identified as the most prevalent symptom (63.8%, CI: 34.5-88.3, I² = 98.8%). At least one gastrointestinal symptom was reported in 69.2% of patients (CI: 49.3-85.9, I² = 97.5%), including abdominal pain (58.3%, CI: 36.0-78.9, I² = 96.0%), diarrhea (41.7%, CI: 22.3-62.5, I² = 93.4%), nausea (39.1%, CI: 29.2-49.6, I² = 79.1%), and vomiting (31.1%, CI: 21.9-41.2, I² = 70.4%). Tick bite history was recalled by 78.7% (CI: 46.4-98.1; I² = 99.1%), and 91.8% (CI: 84.6-96.8; I² = 70.3%) had symptom onset ≥ 1 h post red meat intake. Symptomatic improvement was observed in 86.5% (CI: 73.9-95.4, I² = 80.9%) of patients, with complete resolution in 42.7% (CI: 26.4-59.8, I² = 73.8%).

Conclusion: AGS typically presents with delayed onset allergic and GI symptoms after red meat intake, often with tick bite history. Majority of patients report symptomatic improvement on follow-up.

Background and aims: In patients with achalasia, we hypothesized that visceral hypersensitivity arising from concomitant disorders of gut-brain interaction (DGBI) may influence clinical presentation and response to therapy. Thus, in patients with achalasia, we assessed the clinical manifestations and response to peroral endoscopic myotomy (POEM) as well as the association with concomitant DGBI.

Methods: In 52 consecutive patients with achalasia who underwent POEM, we assessed gastrointestinal (esophageal and nonesophageal) and extraintestinal symptoms utilizing the Structured Assessment of Gastrointestinal Symptoms Instrument (SAGIS). In addition, the response to POEM was assessed with the Eckardt Score.

Results: Patients with type-III achalasia had a greater prevalence of psychological co-morbidities than type-I patients (77.78% vs. 21.43%, p = 0.01). Pre-POEM, patients with type-III achalasia had significantly more severe IBS-type symptoms of constipation and diarrhea when compared with type-I (p < 0.05). The POEM procedure reduced the mean Eckardt scores in patients with type-I (9.00 ± 2.18 vs. 1.00 ± 1.038, p < 0.0001), type-II (9.28 ± 2.234 vs. 1.59 ± 1.547, p < 0.0001), and type-III (7.67 ± 1.871 vs. 2.78 ± 2.635, p = 0.002). Based on the improvement of the Eckhardt score, 87% (45/52) responded to POEM. In type-III patients (5/9), inferior response was noted compared to type-I (14/14 patients, p = 0.01) and type-II (26/29, p = 0.04). Total SAGIS score decreased post-POEM in patients with type-I (baseline 18.29 ± 10.80 vs. post-POEM 8.643 ± 11.76, p = 0.001), and type-II (29.55 ± 18.53 vs. 12.69 ± 15.61, p < 0.0001), but not in type-III (baseline 34.22 ± 19.31 vs. post-POEM 23.22 ± 14.00, p = 0.18).

Conclusion: Our findings suggest that altered gut-brain interactions play a role in the clinical manifestations of patients with achalasia, particularly in patients with type-III, and affect the response to therapy.

Background: Disorders of gut-brain interaction (DGBI), such as functional dyspepsia and irritable bowel syndrome, are characterized by immune activation and increased permeability in the gastrointestinal tract. However, their role in symptom generation remains unclear. Using the normoglycemic Biobreeding diabetes-prone rat (BBDP-N) as a spontaneous model of DGBI, we aim to (1) further characterize the inflammatory infiltrate in the intestinal mucosa and (2) elucidate the relationship between immune activation, barrier function, and colonic sensitivity by studying the effect of a local anti-inflammatory corticosteroid treatment, budesonide.

Methods: Ninety-day-old BBDP-N and control rats were treated with budesonide (0.5 mg/kg/day) or vehicle for 28 days. Jejunal and colonic eosinophil and mast cell numbers and activation were assessed, as well as permeability and colonic sensitivity.

Key results: Eosinophil and mast cell numbers, as well as eosinophil but not mast cell activation were increased in BBDP-N rats. After budesonide treatment, eosinophil and mast cell infiltration decreased. Colonic sensitivity increased over time in BBDP-N rats, which was prevented when treated with budesonide, and a limited effect on permeability in budesonide-treated BBDP-N rats was also observed after treatment.

Conclusions: Together, these results demonstrate that a local anti-inflammatory treatment improved intestinal permeability and visceral hypersensitivity in a preclinical, spontaneous model of DGBI. Moreover, it supports a role for intestinal inflammation in the intestinal barrier defect and symptoms, further paving the way for additional evaluation of anti-inflammatory treatments, including budesonide, in DGBI.