Neurogastroenterology and Motility最新文献

Background: The UCon neurostimulator is a novel device providing dorsal genital nerve (DGN) stimulation for treating fecal incontinence (FI)/fecal urgency (FU). The primary aim was to explore its safety and secondarily its performance, hypothesizing that DGN stimulation would be feasible and safe, while reducing FI/FU.

Method: This was a prospective two-center feasibility study conducted in Denmark. Adults ≥ 18 years, with FI ≥ 1/week, and/or strong FU ≥ 3/week, and a St. Mark's Incontinence Score ≥ 9 were eligible. DGN stimulation was self-administered at home daily for 4 weeks in either a time-limited (30 min/day) or urge/on-demand (60 s upon urgency) modality. Safety was assessed through patient-reported adverse and device-related events. Efficacy was evaluated by comparing baseline data with the last 14 days of the intervention using symptom diaries, the St. Mark's Incontinence Score, and bowel-related quality-of-life measures.

Results: Forty patients consented (39 women), median age 62 years (Q1-Q3: 54-69), and 26 patients completed the study. An adverse and device-related median of 1.5 events per patient was reported, but these were mild and transient. Among patients completing the 4-week intervention, 74% (n = 19) with FI and 43% (n = 14) with strong FU achieved ≥ 50% symptom reduction (p = 0.005 and p ≤ 0.001, respectively). St. Mark's Incontinence Score (n = 26) reduced significantly from 16.0 (13-18) to 11.5 (9-15) (p ≤ 0.001).

Conclusion: Using the UCon neurostimulator in a home setting is safe and feasible. A 4-week stimulation period demonstrated significant positive results in treating FI and FU.

Clinical trials registration: The conducted research was preregistered at ClinicalTrials.gov with the following link: (https://ClinicalTrials.gov/study/NCT05368246?cond=UCon&rank=5).

Background: Irritable bowel syndrome (IBS) is characterized by recurrent visceral pain associated with low-grade gut inflammation. Electroacupuncture (EA) at acupoint ST36 (Zusanli) is reputed to alleviate gastrointestinal disorders, but its effects on IBS-related visceral hypersensitivity and inflammation remain to be fully elucidated. This study evaluated whether EA at ST36 attenuates visceral pain and modulates key inflammatory mediators in the IBS rat model.

Methods: Forty male rats were randomly assigned to Control, IBS model, IBS + EA, and IBS + Sham groups (n = 10 each). IBS was induced by intracolonic acetic acid enema combined with daily restraint stress for 1 week, validating the IBS-D model. EA was applied at bilateral ST36 (2/100 Hz alternating frequency, ~0.5 mA, 20 min) every other day for 2 weeks; sham treatment used superficial needling with no electrical current. Visceral pain was assessed by abdominal withdrawal reflex (AWR) scores and electromyographic responses to graded colorectal distension. Colonic tissues were analyzed for pro-inflammatory cytokines (interleukin-1β, IL-6, tumor necrosis factor-α) by ELISA and for the expression of pain or inflammation-related proteins (TRPV1 and nuclear factor kappa B, NF-κB) by Western blot analyses.

Results: IBS model rats exhibited pronounced visceral hypersensitivity, with AWR scores significantly elevated (e.g., score 3 threshold volume reduced by ~40% vs. controls, p < 0.01). EA at ST36 markedly alleviated visceral pain, increasing pain threshold and reducing AWR scores by ~30%-50% compared to untreated IBS (p < 0.05). EA also significantly downregulated colonic IL-1β, IL-6, and TNF-α levels (by 45%-60% vs. IBS, p < 0.01) and reduced TRPV1 and NF-κB expression toward normal levels.

Conclusion: EA at ST36 produced significant analgesic and anti-inflammatory effects in IBS model rats. Visceral hypersensitivity was blunted and colonic inflammatory biomarkers (cytokines, TRPV1, NF-κB) were suppressed by EA, suggesting that EA at ST36 modulates neuro-immune pathways to relieve IBS-related pain. These findings support the therapeutic potential of ST36-targeted electroacupuncture for managing IBS visceral pain via inflammatory mechanism attenuation.

Background: Polyethilenglicole (PEG), bisacodyl, prucalopride, and linaclotide were demonstrated to be superior to placebo for the treatment of chronic constipation. In a recent study, we reported the actions of PEG, bisacodyl, and prucalopride on colonic motor patterns. The aim of the present study was to evaluate the effect of linaclotide as compared to placebo on colonic motility assessed with high-resolution manometry (HRM).

Methods: In 10 volunteers (30.3 ± 10.6 years), two colonic HRM studies (40 solid-state sensors, 2.5 cm spaced) were performed at least 10 days apart. After 90 min of basal recording, linaclotide 290 μg or placebo was administered orally in double-blind, randomized, cross-over fashion, and the recording continued for 180 min before and after a standardized meal. Colonic motility index (MI) of the right, left colon, and rectum, expressed as a ratio of the baseline value, was compared between treatments by means of a mixed model analysis. The number of high-amplitude propagated sequences, of long-distance propagating sequences, and of pan-colonic pressurizations was compared between treatments.

Results: Linaclotide induced more long-distance propagating sequences than placebo (34.9 ± 41.2 vs. 3.0 ± 5.2, p = 0.026), especially during the meal and post-meal phases of the recording. The total number of pancolonic pressurizations did not differ between treatments. However, a significant increase in the mean number of pre-prandial pancolonic pressurizations was observed following linaclotide administration (p = 0.043). No treatment effect was found on the change in colonic MI from the baseline in any region of the colon.

Conclusions: In healthy controls, acute administration of linaclotide increases the total number of long-distance propagating sequences and the pre-prandial pancolonic pressurizations.

Background: Electroacupuncture (EA) therapy shows promising efficacy in irritable bowel syndrome (IBS). This study integrated nontargeted metabolomics with transcriptomics to investigate the immune-inflammatory mechanisms underlying the effects of EA therapy in male IBS rats.

Method: IBS was induced in rats using water avoidance stress (WAS), and EA was applied at ST25 and BL25 acupoints. The IBS model was evaluated alongside assessments of depressive behavior. Visceral sensation was quantified using the abdominal withdrawal reflex (AWR) and the area under the EMG curve of abdominorectal muscles. The intestinal barrier integrity was analyzed by measuring ZO-1 and MUC2 levels, while inflammation was assessed through IL-1β and TNF-α measurements. Colon samples underwent nontarget metabolomics and transcriptomics analyses, and DEGs were validated using RT-PCR and WB to identify potential pathways. Networks of DEGs and differential metabolites were subsequently constructed to elucidate their interactions.

Result: EA treatment increased the expression of ZO-1 and MUC2, inhibited the IL-1β and TNF-α, and alleviated visceral hypersensitivity and depressive behavior. Transcriptomics identified 13 DEGs, indicating that EA modified the gene expression levels of Lck, Cd28, Il16, Nfatc2, Ccl17, Pik3cd, Zap70, Lat, Cd40, Cxcl10, Tlr9, Tnfsf8, and Tnfsf11. The underlying mechanism may involve the inhibition of PD-1/PD-L1, TCR and NF-κB signaling pathways. Metabolomics identified 14 differential metabolites, suggesting that EA may correct metabolic disturbances.

Conclusion: EA alleviates intestinal damage, inflammation, and behavioral symptoms in male IBS rats, potentially through modulation of immune-inflammatory pathways and metabolic homeostasis. This study focused on male rats; future research including females may clarify sex-related differences in EA.

Background: Chronic cough is a frequent and troublesome extraesophageal manifestation of GERD, with poor response rates to proton pump inhibitors (PPIs) and limited diagnostic tools to predict treatment efficacy. The Lyon score, a novel composite metric integrating reflux parameters, has shown promise in typical GERD but remains untested in chronic cough.

Aim: To evaluate the ability of the Lyon score to predict symptomatic response to double-dose PPI therapy in patients with suspected GERD-related cough.

Methods: We retrospectively analyzed 232 adult patients with chronic cough undergoing upper endoscopy, high-resolution manometry, and 24 h impedance-pH monitoring. PPI response was defined as ≥ 50% reduction in cough severity after ≥ 8 weeks of double-dose PPI therapy.

Results: Among 232 patients, 94 (40.5%) responded to PPIs. Responders had significantly higher Lyon scores (median 7.5 vs. 2.5, p < 0.0001). The Lyon score showed strong predictive performance (AUC 0.769), superior to AET (AUC 0.718) and reflux episodes (AUC 0.602), and comparable to MNBI < 1500 Ω (AUC 0.798). A Lyon score ≥ 5 had 64% sensitivity and 83% specificity. MNBI < 1500 Ω yielded 67% sensitivity and 79% specificity. The combination Lyon score or MNBI < 1500 Ω achieved optimal diagnostic accuracy (sensitivity 79%, specificity 71%, Youden index 0.50), significantly outperforming the combination Lyon score or AET > 6% (p < 0.0001). AET > 6% remained highly specific (93%) but had poor sensitivity (43%).

Conclusion: The Lyon score is a useful tool to identify GERD-related chronic cough responsive to PPI therapy. The presence of low MNBI further improves the prediction of PPI response, supporting integration in reflux work-up for chronic cough.

Background: Quantitative data on colon length in adult chronic constipation (CC) are lacking. This study aimed to measure the length of the colon in CC, in the undisturbed state and after an osmotic laxative challenge, using magnetic resonance imaging (MRI) as compared to healthy volunteers (HV) and IBS-C patients.

Methods: Segmental and total colon length were measured by manual tracing on fasting MRI scans, retrieved retrospectively for 57 HV, 17 CC, and nine patients with irritable bowel syndrome with constipation (IBS-C). In all CC patients and 22 HV, MRI scans were also performed after an oral osmotic laxative challenge. Participants' age range was 18-75 years.

Key results: CC patients showed significantly longer colons (162 ± 6 cm) than HV (127 ± 2 cm; p < 0.01), with 10/17 being longer than the upper limit of normal. Colon length in IBS-C (129 ± 6 cm) was similar to HV. The colon in HV was able to elongate from 133 ± 3 to 148 ± 4 cm (p < 0.0001) to accommodate the macrogol challenge influx, while the CC colon could not do so (from total length at baseline 162 ± 6 to 168 ± 5 cm; p = 0.0768).

Conclusion & inferences: The study provides normative values of colon length, to which CC and IBS-C are compared. CC was associated with increased colon length and reduced capacity to elongate longitudinally, rather than radially, in response to a laxative challenge. Colon length in IBS-C was similar to HV. These measurements can improve our understanding of gut disease pathophysiology and response to treatment.

Thank you for your insightful comments, which have expanded our research perspective from psychology to neural mechanisms. We agree that the core challenge of refractory constipation is closely related to neurological factors, and its essence lies in being a complex disorder involving sensory and neural dysregulation. Our preliminary fMRI studies have already identified abnormal functional connectivity in the brains of patients. Clinical observations suggest that different patient subtypes may correspond to distinct pathological mechanisms, necessitating differentiated diagnostic and therapeutic strategies. Future research will integrate psychological, neural, and physiological dimensions to construct a multidimensional pathological model.

Background & aims: The straight leg raise (SLR) is a provocative maneuver used to assess the esophagogastric junction (EGJ) barrier function during high-resolution manometry (HRM) and is part of the Milan Score (MS). The Chicago Classification 4.0 (CCv4.0) protocol requires patients to perform a supine-upright transition (SUT), increasing intra-abdominal pressure (IAP). The aim of this study was to compare the SUT and SLR maneuvers for efficacy in increasing IAP and in predicting pathologic gastroesophageal reflux disease (GERD).

Methods: Consecutive adult patients with persistent GERD symptoms undergoing HRM and pH-impedance were prospectively enrolled. After completion of the supine swallows of the CCv4.0 protocol, the SLR maneuver was performed and the patients were asked to get up to the upright position (SUT). IAP and intra-esophageal pressure (IEP) were recorded at baseline and during the maneuvers. GERD was defined as acid exposure time > 6% according to Lyon 2.0.

Results: Among the 110 patients included (age 55 years; 59.1% female, BMI 25.4 kg/m²) SUT was effective in 94 and SLR in 85. SUT was more sensitive than SLR (77.4% vs. 71.0%) but less specific (63.5% vs. 79.6%) in predicting GERD. On ROC analysis, the AUC of the MS-SUT was 0.825 and MS-SLR 0.854. When both maneuvers were effective (73 patients) SUT predicted GERD in 69.9%, SLR in 76.7% (p = 0.192). When concordant (52 patients) sensitivity and specificity were 88% and 80%, and the AUC of the MS was 0.872.

Conclusions: SUT is comparable to SLR, with higher sensitivity but lower specificity. When both are concordant, the SUT can strengthen confidence in SLR and increase the accuracy of the Milan Score.

Background: Irritable bowel syndrome (IBS), a disorder of the gut-brain interaction, is associated with significant symptom burden and impaired psychosocial functioning. Evidence-based behavioral therapies are effective, but often underutilized due to accessibility barriers. Mobile health is an emerging field with the potential to bridge the gap between the needs of individuals with IBS and the limitations of the healthcare system. This study evaluated the feasibility and effectiveness of the LyfeMD app plus health coaching (HC) in improving IBS symptom severity and psychosocial wellbeing.

Methods: This 12-week interventional pilot study evaluated the effectiveness of a mobile application combined with HC in adults diagnosed with IBS. Participants were assessed at baseline, 6 weeks, and 12 weeks using validated surveys to assess symptom severity, psychosocial wellbeing, diet, physical activity, and sleep. A Fitbit was also used to track physical activity and sleep.

Results: Thirty-nine participants completed the 12-week intervention. IBS symptom severity improved significantly (p < 0.001) over the 12-week period, with 63.2% of the participants having a clinically meaningful improvement in their symptoms. In addition to symptom severity, participants improved in all measured psychosocial domains and their subjective sleep quality at 12 weeks.

Conclusion: In summary, the LyfeMD platform, in combination with HC, shows potential in improving IBS symptom severity, psychosocial well-being, and sleep quality in individuals diagnosed with IBS. These findings highlight the potential of mobile health as a complement to traditional medical care. Further research, including randomized controlled trials with extended follow-up, is needed to confirm findings and the sustainability of these outcomes.

Background: Arbutus and hawthorn fruits are commonly utilized in traditional medicine to address various gastrointestinal (GI) ailments. Our primary aim was to individually assess the effects of aqueous extracts from Arbutus unedo (AUAE) and Crataegus monogyna (CMAE) fruits on GI motility, spontaneous jejunal smooth muscle contractility, and hyperglycemia management.

Methods: Wistar rats were administered loperamide (LOP, 3 mg/kg, b.w.) along with AUAE or CMAE (at doses of 75, 150 and 300 mg/kg, b.w.) or yohimbine (YOH, 2 mg/kg, b.w.). GI transit was evaluated using the charcoal meal test. The impact of both extracts on jejunal secretion and contraction was assessed using the Ussing chamber technique and the isometric transducer. The bioactive constituents of AUAE and CMAE were analyzed via liquid chromatography-high resolution electrospray ionization mass spectrometry (LC-HRESIMS).

Results: AUAE and CMAE comprise bioactive compounds, including phenolic acids, flavonoids, and flavonols, capable of eliciting various intended physiological effects. Both extracts demonstrated a significant and dose-dependent increase in GI transit (77.33%-89.83% and 80.31%-85.54%, respectively) compared to the delayed peristalsis induced by LOP (42.77%) and the accelerated effect of YOH (90.09%). Both extracts induced an increase in the amplitude of spontaneous jejunal contraction with an EC₅₀ of 90.47 and 22.98 μg/mL, respectively. Conversely, the two extracts did not impact the electrogenic transport of intestinal fluid when compared to the action produced by forskolin (FSK, 10 μM). Additionally, both extracts significantly reduced glucose levels in hyperglycemic rats compared to control values.

Conclusion: These findings hold promise for the development of novel preventive and pharmacological treatment strategies for GI disorders and diabetes management.