Neurogastroenterology and Motility最新文献

Background: Postoperative ileus (POI) is a common complication after abdominal operation, which is characterized by delayed gastrointestinal motility that can lead to prolonged hospitalization. Previous studies have demonstrated that gut microbiota and macrophages are involved in POI pathogenesis, but the underlying mechanism and the role of probiotics in it are still unclear. This work investigated the prophylactic effect of Lactobacillus reuteri (L. reuteri) DSM 17938 administration on POI mice.

Methods: Mice were supplemented with antibiotics or L. reuteri DSM 17938 for two weeks before intestinal manipulation surgery. One day after surgery, the small intestine transit rate was evaluated. Samples were collected to determine the intestinal macrophages, histology, cytokines, gut microbiota, and fecal metabolome.

Key result: Results showed that gut microbiota alteration contributed to POI. L. reuteri DSM 17938 increased intestinal motility of POI mice, maintained the proportion of intestinal CX3CR1⁺ macrophage, reduced M1 macrophage, and modulated macrophage-associated cytokines. Additionally, L. reuteri DSM 17938 slightly alleviated gut metabolic disorders but had an effect on a portion of metabolites of fecal tryptophan metabolism, modulated gut microbiota composition and function, and specifically suppressed bacterial invasion of epithelial cells and the expansion of Escherichia coli, which had a negative correlation with the small intestine transit rate in POI mice.

Conclusions and inferences: Our findings indicate that L. reuteri DSM 17938 is a promising probiotic for the prevention of POI, but it still needs further clinical validation.

Background: Certain patients still experience nocturnal reflux symptoms despite taking a standard morning PPI. This study compares the efficacy of adding a wedge pillow versus an evening PPI to the morning PPI for treating nocturnal reflux symptoms.

Methods: This noninferiority randomized trial included patients with ≥ 2/week nocturnal heartburn/regurgitation despite morning PPI use for ≥ 4 weeks. Participants were randomized to either a wedge pillow with morning or twice-daily PPI for 4 weeks. Nocturnal reflux symptoms were assessed using the nocturnal gastroesophageal reflux disease symptom severity and impact questionnaire (NGSSIQ) at Weeks 0, 2, and 4, along with quality of life, daytime sleepiness, and sleep quality. Twenty-four hour pH-impedance monitoring was conducted at baseline and Week 4. Wedge pillow compliance was monitored with a pressure-sensing timekeeper.

Results: Twenty-four patients were enrolled with comparable baseline characteristics and severity of nocturnal reflux. At Week 4, NGSSIQ scores were 30.01 ± 1.97 in the wedge pillow group and 36.33 ± 1.96 in the twice-daily PPI group (mean difference - 6.32; 95% CI -10.28 to 6.21), which falls below the predefined non-inferiority margin demonstrating non-inferiority. Sleep quality was better in the pillow group (5.55 ± 0.56 vs. 7.53 ± 0.60, p = 0.001). Although nighttime median bolus contact time was longer in the twice-daily PPI group [4.3 (2.9-5.4) vs. 7.4 (3.5-15.5) seconds, p = 0.03], other reflux parameters did not show clinically relevant differences between groups. Pillow compliance was high, with 83.3% reporting satisfaction.

Conclusion: Adding a wedge pillow was not inferior to evening PPI for nocturnal reflux symptoms and was associated with greater improvements in sleep quality, despite the absence of clinically relevant differences in reflux parameters, supporting the wedge pillow as a potential alternative for managing nocturnal reflux symptoms.

Trial registration: Thaiclinicaltrials.org: TCTR20240920004.

Background: During endoscopy, which often is the initial diagnostic test performed for esophageal symptoms, a CARS endoscopic score can be calculated and functional lumen imaging probe (FLIP) panometry can be performed. Recently, the combination of a CARS score > 4 calculated from endoscopic videos and non-spastic obstruction on FLIP noted from offline analysis has been found to be highly predictive of disorders of EGJ outflow obstruction (i.e., achalasia and conclusive EGJOO). We aimed to validate these findings based on detailed assessments performed in real time during endoscopy and FLIP panometry with reclassification based on the CARS score and Dallas Consensus for FLIP panometry.

Methods: We reviewed our clinical database to identify patients who had endoscopy with documentation of an esophageal motility examination (i.e., components of the CARS score and FLIP with documented EGJ-diameter/distensibility, contractile response pattern at each volume) and HRM performed at our Center for Esophageal Diseases. CARS scores were calculated from score components documented in the endoscopy report and FLIP panometry classifications were reclassified according to the Dallas Consensus. Manometric diagnosis was based on Chicago Classification v4.0 (CCv4.0).

Key results: In 120 patients (mean age 55.5 years, 66% female), the combination of CARS score ≥ 4 and reduced EGJ opening (REO) on FLIP was highly suggestive of an EGJ obstruction diagnosis (achalasia or conclusive EGJOO) with 100% specificity and 100% positive predictive value.

Conclusions: A CARS score ≥ 4 combined with FLIP-REO obtained in real time during endoscopy is highly predictive of an EGJ obstruction diagnosis (achalasia or confirmed EGJOO) on HRM.

Background: While some patients report full thickness rectal prolapse (RP) exclusively during defecation, others may experience it spontaneously during walking, exercise, and/or all the time. We hypothesized that patients with RP only during defecation have more preserved physiological and anatomical characteristics and aimed to identify the phenotypes of patients with various RP expression.

Methods: A retrospective analysis of a prospectively maintained registry of women with RP (2017-2023) included clinical characteristics, MRI defecography (MRD), and high-resolution anorectal manometry (HR-ARM).

Key results: Of 297 patients, 147 (49%) experienced defecation-only RP, while 150 (51%) had spontaneous RP. The defecation-only RP group was younger (p < 0.001) and exhibited higher obstructive defecation syndrome (ODS) scores (p < 0.001), associated with higher rectal pressures at simulated defecation. The spontaneous RP patients had higher Wexner fecal incontinence scores (p < 0.001) and were more likely to seek medical care within 6 months of symptom onset (p = 0.006). On MRD, they had larger levator hiatus length, width, and bowl volume along with a wider anorectal angle. HR-ARM showed lower resting anal pressures (p = 0.03) and less sustained squeeze pressures (p = 0.04) in this group.

Conclusions and inferences: Defecation-only RP appears to represent a distinct phenotype, potentially an early stage of RP, characterized by younger age, more severe obstructive symptoms, more preserved anal sphincter function, and less pelvic floor laxity. Future research should focus on risk factors for progression to more sustained RP and the potential benefits of early intervention in patients with defecation-only RP.

Background and aims: Chronic intestinal pseudo-obstruction (CIPO) occurs in up to 40% of patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). While enteric nervous system abnormalities have been documented, 15%-38% of CIPO cases show normal histology, suggesting alternative pathogenic mechanisms. We aimed to investigate smooth muscle pathology in MELAS-associated CIPO.

Methods: Comprehensive pathological examination including light and electron microscopy was performed on autopsy material from a 52-year-old male with MELAS (m.3243A > G mutation) and recurrent intestinal obstruction symptoms. Gastrointestinal tissue from the entire digestive tract was analyzed and compared with age-matched control tissue.

Key results: Histological examination revealed widespread vacuolization and pallor of gastrointestinal smooth muscle throughout the digestive tract (esophagus, stomach, duodenum, and colon). Electron microscopy demonstrated abundant abnormal mitochondria in smooth muscle cells and, notably, marked loss of myofilaments in the colonic muscle. The ultrastructural preservation was limited by postmortem changes (autolysis, occurring approximately 4 h after death) and the re-embedding technique from formalin-fixed paraffin-embedded tissue; however, the striking difference was evident compared to age-matched controls. Similar abnormalities were observed in the Auerbach plexus.

Conclusions and inferences: This represents the first report of myofilament loss in MELAS-associated CIPO, suggesting that mitochondrial dysfunction may directly impair smooth muscle contractile apparatus beyond previously described neuronal abnormalities. These findings provide novel insights into CIPO pathogenesis and may inform therapeutic strategies emphasizing early enteral nutrition interventions that bypass affected gastrointestinal segments.

Background: Enteroendocrine cells (EECs) are dispersed along the intestinal mucosa and transduce luminal stimuli into hormonal signals. EECs exhibit neuron-like features and express both α-synuclein and tau, two proteins pathologically and genetically linked to Parkinson disease (PD). These observations support the hypothesis that EECs may be involved in disease development in the "body-first" PD subtype. Cellular models represent invaluable tools for studying the role of α-synuclein and tau in PD pathogenesis. However, the sensitivity and specificity of commercial antibodies for detecting α-synuclein and tau in EEC cell lines remain unclear.

Methods: We tested by immunoblot a panel of commercial total-α-synuclein and total-tau antibodies on protein lysates from three EEC cell lines: GLUTag, NCI-H716, and STC-1. Pharmacological and biochemical manipulations were applied to assess the specificity of antibodies against phosphorylated α-synuclein and tau.

Key results: Five antibodies detected total α-synuclein in NCI-H716 lysates, whereas the antibodies D1M9X and Tau12 detected total tau in GLUTag and NCI-H716 lysates, respectively. α-synuclein and tau protein levels were comparable between naïve and differentiated NCI-H716 cells. Four phospho-specific antibodies revealed phospho-α-synuclein S129 in NCI-H716. Of the nine phospho-tau antibodies tested, six recognized tau phosphorylated at specific epitopes (T181, S199, T231, S356, S396, and S404) in GLUTag cells.

Conclusions and inferences: Our results indicate that NCI-H716 cells represent an ideal EEC model for studying α-synuclein expression and phosphorylation, whereas GLUTag cells are preferable for investigating tau protein biology. This work provides a comprehensive antibody toolbox to dissect the physiological and pathological role of α-synuclein and tau in EECs.

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: Patients with gastric dysmotility exhibit abnormal transit and reduced contractility, for which quantification is limited with current methodologies. The Atmo Capsule is a wireless motility capsule that measures regional gastrointestinal transit. We tested its technical capabilities to evaluate gastric contractility by detecting changes in capsule acceleration during transit.

Methods: Data from 91 healthy controls and 182 patients with suspected dysmotility who ingested the Atmo Capsule following a standardized protocol were included. Gastric emptying times (GET) ≥ 5 h were considered delayed. Contraction frequencies (cycles per minute [cpm]) and amplitudes (as arbitrary units [au]) were identified following Fast Fourier Transformation of accelerometer data using 5-min windows and were assessed in 30-min windows post-ingestion (early gastric phase) and before gastric emptying (late gastric phase). Data were compared via ANOVA, using Bonferroni corrections, between healthy controls, patients with normal gastric emptying, and patients with delayed gastric emptying.

Key results: Gastric emptying was delayed in 53/182 (29%) patients. Three cpm contraction frequencies were identified across both gastric phases in controls and patients. Contraction amplitudes did not differ between groups in the early gastric phase. In the late phase, mean amplitudes were lower in patients with delayed gastric emptying (6.4 au) compared with subjects with normal gastric emptying (controls, 9.7 au, p < 0.0001; patients, 8.6 au, p < 0.0001).

Conclusions & inference: The Atmo Capsule enables precise quantification of gastric contraction profiles, permitting differentiation of normal from pathological motor patterns. Findings of this technical assessment support its potential for evaluating gastric physiology and detecting pathophysiological patterns of gastric dysmotility.

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.

Background: Colonic inflammation is known to cause intestinal dysmotility. We examined the possible involvement of descending monoaminergic neurons projecting to the lumbosacral spinal cord in colorectal dysmotility using a rat model of colitis.

Methods: Colitis was induced in rats by intracolonic administration of 2,4,6-trinitrobenzenesulfonic acid. Motility in inflamed and noninflamed colorectal regions was assessed in vivo under anesthesia.

Key results: Colonic inflammation suppressed colorectal motility responses to noxious stimulus applied on inflamed colonic regions. The suppressed responses recovered as inflammation improved. In a subset of rats with colitis, basal motility in noninflamed regions was significantly enhanced, and this was abolished by intrathecal administration of serotonergic and dopaminergic receptor antagonists to the lumbosacral spinal cord. In some rats, enhanced basal motility spontaneously subsided then returned to a hyperactive state. The re-enhanced basal motility was also suppressed by monoaminergic receptor antagonists, suggesting intermittent activity of the descending monoaminergic neurons.

Conclusions and inferences: This study suggested that persistent noxious input from an inflamed colon activates descending monoaminergic neurons, leading to enhanced basal motility in noninflamed regions. Our findings provide important insights into the pathophysiology of inflammation-associated dysmotility.