Neurogastroenterology and Motility最新文献

Background: Epilepsy is a chronic neurological disorder primarily affecting the central nervous system. However, growing evidence suggests that epilepsy also impacts peripheral organs, including the gastrointestinal tract. The intestinal barrier, essential for maintaining homeostasis and immune defense, is particularly susceptible to oxidative stress, which can disrupt junctional proteins, leading to increased permeability and barrier dysfunction. This study aimed to investigate the effects of epilepsy on duodenal morphology and intercellular junction integrity, as well as to evaluate the potential protective role of Rosa Canina Seed Oil (RSO) in mitigating these alterations.

Methods: A pilocarpine-induced rat model of epilepsy was employed in 47 male Sprague-Dawley rats, randomly assigned to eight experimental groups, and treated intragastrically with Rosa canina seed oil (RSO) at doses of 0.125, 0.25, or 0.5 mL/rat/day prior to epilepsy induction. Histomorphometric analysis was conducted to assess villus height, crypt depth, and mucosal surface area. Immunohistochemical staining was used to evaluate the expressions of key junctional and cytoskeletal proteins, including zonula occludens-1 (ZO-1), E-cadherin, and vimentin. Correlation analysis was performed to explore associations between morphological parameters and protein expression levels.

Results: Epileptic rats exhibited significant reductions in villus height, crypt depth, and absorptive surface area, along with downregulation of ZO-1, E-cadherin, and vimentin, indicating compromised barrier function. RSO treatment demonstrated a dose-dependent protective effect, with moderate and high doses partially restoring intestinal morphology and tight junction integrity. Notably, higher doses of RSO significantly restored ZO-1 levels and preserved vimentin expression, suggesting its role in stabilizing the epithelial barrier and cytoskeletal framework. Correlation analysis confirmed a strong association between epilepsy-induced structural disruptions and barrier dysfunction (p < 0.05), highlighting the potential protective effects of RSO.

Conclusion: These findings demonstrate that epilepsy impairs intestinal barrier integrity by altering epithelial structure and junctional protein expression, leading to increased permeability. RSO treatment partially counteracted these effects, supporting epithelial stability and barrier function in a dose-dependent manner.

Introduction: Gastrointestinal (GI) motility is controlled by the coordinated activity of enteric neurons, glial cells, and resident muscularis macrophages (mMφs). Apolipoprotein E (ApoE) is highly expressed in mMφs, but its functional role in the gut remains unclear. We hypothesized that mMφ-derived ApoE regulates intestinal motility under physiological and stress conditions.

Methods: Global ApoE knockout mice, bone marrow chimeras, and macrophage-specific ApoE-deficient mice were used to assess the impact of ApoE loss on gut transit, immune response, and neuromuscular integrity in both homeostatic and postoperative ileus (POI) settings.

Results: (1) Single-cell RNA sequencing revealed that muscularis macrophages highly express ApoE, with further upregulation after intestinal manipulation. (2) Bone marrow chimera experiments showed that hematopoietic-derived ApoE only partially contribute to the maintenance of gut motility. (3) Global ApoE deficiency led to mild impairment of intestinal transit and increased glial activation, accompanied by an expansion of the macrophage population and elevated gene expression of inflammatory cytokines. (4) Macrophage-specific deletion of ApoE did not affect gastrointestinal transit or tissue morphology under normal conditions.

Conclusion: Although highly expressed and dynamically regulated in muscularis macrophages, ApoE is largely dispensable for intestinal neuromuscular function at baseline and during postoperative ileus.

Background and aims: Esophagogastric junction (EGJ) integrity influences gastroesophageal reflux disease (GERD) pathophysiology, but its association with positional reflux patterns remains unclear. This study evaluated whether upright and recumbent acid exposure differs based on EGJ status on high-resolution manometry (HRM).

Methods: Retrospective study of patients undergoing HRM and 24-h pH-impedance monitoring off-therapy. EGJ was defined disrupted if any of the following HRM features were present: type II/III morphology, basal pressure < 10.4 mmHg, or EGJ-CI < 9.6 mmHg·cm; intact otherwise. Acid exposure time (AET) and additional reflux metrics were calculated in both positions. Conclusive GERD was defined per Lyon 2.0 (AET > 6%).

Results: Among 283 patients, 102 (36%) had a disrupted EGJ. These patients showed higher total AET (4.7% vs. 1.9% in the intact EGJ, p < 0.001), primarily driven by recumbent exposure (1.9% vs. 0.2%, p < 0.001). In patients with conclusive GERD (n = 91), total and upright AET were similar across EGJ subgroups, while recumbent AET was significantly higher in the disrupted EGJ group (11.5% vs. 3.1%, p < 0.001). Pathologic recumbent AET (> 6%) and severe esophagitis (LA C-D) were observed only in patients with disrupted EGJ (72% vs. 0%, p < 0.001; 14% vs. 0%, p = 0.015, respectively).

Conclusion: EGJ integrity stratifies GERD phenotypes by positional pattern: upright-predominant in patients with intact EGJ and recumbent-predominant in those with disrupted EGJ, the latter also associated with severe esophagitis. This suggests distinct pathophysiologic GERD mechanisms depending on EGJ integrity and may guide personalized management.

Background: Gastric emptying (GE) scintigraphy with 4-h imaging and a radiolabeled chicken egg-based meal (320 kcal, 30% fat) is the standard test for gastroparesis at Mayo Clinic, with an intraindividual coefficient of variation (COV_intra) of 23.8% for GE half emptying time (T_1/2). Alternative meals for patients with dietary restrictions, including egg allergies or vegan diets, are lacking, limiting test accessibility. The study aimed to establish a vegan, lactose-, nut-, and gluten-free meal with similar caloric and fat content to the egg meal and to assess its performance in GE studies.

Methods: In Vitro: ^99mTc binding to egg meal over 4 h was compared to a calorically and nutritionally similar vegan alternative, JUST Egg, using a validated in vitro model simulating gastric conditions of pH, pepsin, and stirring. In Vivo: 10 healthy participants underwent randomized crossover GE scintigraphy with standard and vegan meals, spaced ≥ 3 days apart to measure GE% at 2 h, 4 h, and GE T_1/2. Group comparisons and variance analysis included Rank Sum tests and Bland-Altman plots.

Key results: In Vitro: A strong correlation (R = 0.975, p-value < 0.01) between ^99mTc binding in the egg and vegan egg models was observed. Minimal variance (< 10%) was recorded at all time points. In Vivo: GE at 4 h and GE T_1/2 showed non-statistically significant mean differences, < 2% and < 10 min respectively, between both meals. The intra-individual variability was 18.8%.

Conclusions and inferences: The vegan meal demonstrated in vitro stability, in vivo performance comparable to the egg meal, and a COV_intra of 18.8%, which was lower than the 23.8% reported in repeat egg meal GE studies.

Trial registration: ClinicalTrials.gov number NCT06991036 (https://clinicaltrials.gov/study/NCT06991036?term=NCT06991036&rank=1).

Background: Disorders of gut-brain interactions (DGBI) are increasingly prevalent in children and adults and can significantly impact quality of life starting in childhood and extending into adulthood. DGBI encompass a range of gastrointestinal symptoms in the absence of identifiable structural etiologies with biopsychosocial implications. Ongoing research efforts aim to understand the etiology and pathophysiology of DGBI, with disruptions of the gut-brain axis leading to visceral hypersensitivity and hypervigilance believed to be involved in symptom manifestation. Currently, there are 17 pediatric DGBI that are diagnosed via the Rome IV criteria. However, there is a paucity of research evaluating the clinical presentation, diagnosis, and management of pediatric patients with DGBI and concurrent structural gastrointestinal conditions despite the significant symptom overlap and diagnostic challenges.

Purpose: This summative review will aid clinicians by providing an updated overview of pediatric studies assessing the overlap between DGBI and inflammatory bowel disease, celiac disease, and eosinophilic gastrointestinal disorders. Functional abdominal pain, irritable bowel syndrome, and functional constipation are common DGBI subtypes in pediatric patients with underlying structural gastrointestinal disorders. It is imperative that clinicians be cognizant of this overlap, particularly when gastrointestinal symptoms persist despite appropriate management of structural conditions. In such cases, a multidisciplinary approach may be necessary if there is concern for a comorbid DGBI to provide comprehensive care for patients and to improve quality of life, provider satisfaction, and successful clinical outcomes.

Background: The pathophysiology of rumination syndrome is not entirely elucidated. We aimed to assess gastric emptying and fundic accommodation through solid gastric emptying scintigraphy in children with rumination syndrome and explore the relationship between scintigraphic findings and high-resolution impedance esophageal manometry results.

Methods: Gastric retention at 1, 2, 3, and 4 h from standardized meal ingestion were measured. Delayed gastric emptying was defined as gastric retention > 10% at 4 h. The ratio of gastric counts in the proximal stomach to those in the entire stomach measured immediately after meal ingestion (IMD⁰) was used as a marker of fundic accommodation. A value of < 0.568 defined an impaired fundic accommodation. The number of rumination episodes occurring during the first postprandial hour of manometry recording were calculated.

Results: Among 33 children included (median age: 14 years) 10 (30%) had impaired fundic accommodation and 12 (36%) delayed gastric emptying. Children with impaired fundic accommodation have a higher median number of rumination events [10 (IQR 7-12) vs. 6 (IQR 4-89); p = 0.03] recorded during the first postprandial hour. Similarly, at 1-h children with delayed gastric emptying have a higher median number of rumination events [12 (IQR 10-13) vs. 6 (IQR 3-8); p = 0.0004]. The number of rumination events was inversely related to IMD⁰ (p = 0.03; r = -0.4) and directly related to gastric retention at 1-h in the whole stomach (p = 0.003; r = 0.5), fundus (p = 0.03; r = 0.4) and antrum (p = 0.02; r = 0.4).

Conclusion: More than half of children with rumination syndrome included in our study present an abnormal gastric motor function on solid-meal gastric emptying scintigraphy that might contribute to the occurrence of rumination episodes. The detection of these abnormalities might enhance targeted clinical trials and patient management.

Background and aims: Achalasia classifications, such as the Chicago Classification subtypes based on high-resolution manometry (HRM) and Japanese Esophageal Society (JES), Italian, or Brazilian classifications based on esophagram, have been described. We aimed to compare these schemes for prediction of achalasia treatment outcomes.

Methods: 222 adult patients with achalasia that completed pretreatment HRM and esophagram before and after treatment were included. Pretreatment HRM achalasia subtypes were determined by the Chicago Classification and JES; Italian and Brazilian classifications were defined by pretreatment esophagram. Post-treatment outcomes were defined using the Eckardt symptom score (good outcome < 4) or timed barium esophagram (TBE; good outcome 5-min column height < 5 cm).

Results: The Chicago Classification was a significant predictor of symptomatic outcome (p = 0.003-0.007), whereas JES, Italian, and Brazilian schemes were not. All four classifications were significant predictors of radiographic outcome, with JES demonstrating the best model fit as identified by lowest Akaike information criteria (AIC). Type III achalasia (Chicago Classification) patients had the lowest rates of good symptomatic outcomes despite treatment primarily with POEM, whereas advanced esophagram stages (JES-C, Italian IV, Brazilian 2-3) were associated with poorer radiographic outcomes.

Conclusions: Both HRM- and esophagram-based classification schemes predict achalasia treatment outcomes, though with different strengths. While treatment choice may impact outcomes, HRM best predicted symptomatic outcomes, while esophagram classifications better predicted objective radiographic outcomes. Utilizing both modalities may enhance prognostication of outcomes in achalasia.

Background: Recent work suggests an altered duodenal mucosa-associated microbiota (d-MAM) in patients with functional dyspepsia (FD) when compared to controls. This may reflect alterations in host-microbiome homeostasis. Given the specific mucosal immune signatures identified in FD, we hypothesize that these signatures are associated with specific microbial changes. We aim to profile the d-MAM to identify microbes associated with known changes in FD mucosal and peripheral immunity.

Methods: Upper gastrointestinal biopsies were collected from 11 outpatient controls and 17 FD patients. Specific biopsies were collected for 16S rRNA sequencing, histology, and mucosal lamina propria mononuclear cell (LPMC) isolation. Where available, peripheral blood mononuclear cells (PBMC) were isolated. PBMC and LPMC populations were analyzed for T-cell populations by flow cytometry.

Key results: Comparing the histological and immune measures between FD and controls revealed significant differences with decreased villi goblet cells and increased LPMC CD4 Central Memory, LPMC CD8, and PBMC CD4+ Central Memory Th17 in FD patients. Specific microbiome associations found that in controls, villi goblet cells positively correlated with Massilia and negatively with Exiguobacterium. Additionally, controls had a negative correlation between LPMC CD4 Central Memory and Veillonella. Notably, FD patients demonstrated a significant negative correlation between LPMC CD8 and Sulfophobococcus, and a positive correlation between PBMC CD4+ Central Memory Th17 and both Gemella and Fusobacterium.

Conclusions and inferences: Our findings contribute to a growing body of evidence, indicating FD patients exhibit distinct alterations in d-MAM and immune profiles compared to controls. Furthermore, the immune-microbiome associations within control populations were absent in FD patients, suggesting a loss of host-microbiome homeostasis that may contribute to FD pathophysiology.