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 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: Evacuation dysfunction affects gastrointestinal motility, yet its effect on small bowel microbiota is unknown. We aimed to compare the glucose breath test (GBT) and lactulose breath test (LBT) outcomes in patients with or without evacuation dysfunction based on high-resolution anorectal manometry (HR-ARM) and balloon expulsion test (BET).

Methods: We conducted a retrospective review of patients who received a HR-ARM and either a GBT or LBT from 2018 to 2024.

Key results: We studied 344 patients who underwent GBT and 144 who underwent LBT. Clinical characteristics between the two groups were comparable. Abnormal BET was observed in 53% of patients. Rates of abnormal breath tests were comparable among patients with or without abnormal BET. Patients with positive vs. negative breath tests had similar anorectal pressures, rectal sensory function, and BET results. There were significantly more negative breath tests in GBT (64%) versus LBT (35%), with higher rates of small intestinal bacterial overgrowth (SIBO) in LBT versus GBT (SIBO only: 20.1% vs. 7.6%; SIBO+IMO: 21.5% vs. 5.5%; p < 0.001).

Conclusions and inferences: The presence of evacuation dysfunction does not impact the results of the breath test. HR-ARM and BET demonstrate a high diagnostic yield in identifying the etiology of abdominal bloating in patients with chronic constipation or IBS without diarrhea, whereas hydrogen breath tests have a low diagnostic yield in this context. The specificity and sensitivity of LBT in this patient population remain less certain.

Introduction: A significant, yet often overlooked, complication of subarachnoid hemorrhage (SAH) is the development of acidosis. Denervation atrophy is a recognized cause of neural ganglion damage following primary motor neuron damage, but the effect of tissue pH changes has not been thoroughly investigated.

Aim: This study investigates whether acidosis causes Auerbach ganglia damage following SAH.

Methods: Twenty-four hybrid rabbits were selected, and five (GI; n = 5) were used for the analysis of the Auerbach ganglia. Six animals (GII; n = 6) were allocated to the SHAM group, receiving 1 cc of saline. The remaining 13 animals (GIII; n = 13) were allocated to the study group, receiving 1 cc of autologous arterial blood injected into the cisterna magna to induce subarachnoid hemorrhage under general anesthesia. Blood pH values were recorded before the experiment, on the seventh day, and immediately before sacrifice. Animals were sacrificed after 1 week, and the degenerated neuron density of the Auerbach ganglia in 1 cm segments of the ascending colon was estimated. The pH values and degenerated Auerbach ganglia neuron densities (n/mm³) were compared using the Mann-Whitney U test.

Results: The presurgical blood pH values of all animals were 7.431 ± 0.032. On the seventh day, pH values were 7.403 ± 0.052 in GI; 7.395 ± 0.024 in GII; and 7.264 ± 0.045 in GIII. At the end of the experiment, pH values were 7.431 ± 0.037 in GI; 7.395 ± 0.062 in GII; and 7.330 ± 0.035 in GIII. Degenerated neuron densities of Auerbach ganglia neurons were 13 ± 4 in GI, 34 ± 6 in the SHAM group, and 87 ± 15 in GIII. The p values were: p < 0.005 for GII/GI; p < 0.0001 for GII/GIII; and p < 0.00005 for GI/GIII.

Conclusion: Acidosis is a potential causative factor of Auerbach ganglia degeneration following SAH, a phenomenon not previously described.

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: The reference standard for the assessment of esophageal motility and sphincter function is high-resolution esophageal manometry (HRM). Diagnostic values for HRM are determined by the Chicago Classification (CC v4.0), which is based almost entirely on distal esophageal function without measures to address the proximal esophageal segment. Therefore, we sought to determine normal HRM values for proximal esophageal function when obtained in the standard HRM positions (supine and upright).

Methods: Healthy, asymptomatic adults (≥ 18 years) were recruited. All participants completed a standard protocol. CC v4.0 measurements, along with a proximal contractile integral (PCI) (millimeters mercury-seconds-centimeters[mmHg-s-cm]), temporal measures of proximal and distal contractility (seconds), and lengths of proximal and distal esophagus (centimeters), were performed. Summary statistics, tests of normality, and paired two-sided t-tests were performed.

Results: HRM data from 30 participants were included. Mean supine PCI was 423.9 mmHg-s-cm with a mean contraction time of 3.2 s and a mean length of 5.5 cm. The mean upright PCI was 183.9 mmHg-s-cm with a mean contraction time of 2.2 s, and a mean length of 4.5 cm. All proximal values were significantly different comparing the two positions (PCI p < 0.0001; time p < 0.0001; length p < 0.0001). All distal measurements fell within the ranges of normal, and all measures for contractile integral, contraction time, and contraction length were statistically significantly different (p < 0.0001 for all) comparing proximal versus distal measurements.

Conclusions: These preliminary data represent our first attempt to quantify normal proximal esophageal function using HRM measurements of contractile vigor, contraction length, and time.

Background: Colon displays structural and functional diversity. However, the region-specific motility effects of spinal nerves on the colon are unclear. We mapped the regional colonic motor response to thoracolumbar (T12-L1) (TLNS) and sacral (S1-S4) (SNS) roots nerve electrical stimulation (ES) in an anesthetized porcine model, with or without concomitant afferent (AB) or efferent (EB) transmission block.

Methods: Adult male Yucatan pigs (n = 16) underwent a laminectomy followed by unilateral (left root) SNS (S1-S4, 30 Hz, 0.3 ms, 0.5 mA, PT, 30 s ON/90 s OFF) or with concomitant AB or EB (40 kHz, 0.1 ms, 2 mA). In a separate group (n = 7), TLNS (T12-L1, 10 Hz, 0.3 ms, 0.5 mA, continuous or 30 Hz, 0.3 ms, 0.5 mA, PT, 30 s ON/90 s OFF) of the left root concomitant with or without EB was applied. Proximal (pC), transverse (tC), distal (dC) colon and anal canal (AC) luminal manometry were monitored before, during and after stimulation. Area under the curve of contraction (AUC), luminal pressure heat maps, and contraction spectral analysis were analyzed.

Key results: S2 ES increased the power of the contraction frequency spectrum in both dC and AC during stimulation and increased the AUC of contraction in dC and AC during and post-stimulation. AB and EB partially reduced dC, while EB abolished the increase in AC. In contrast, S1, S3, or S4 ES as well as TLNS had little effect on motility.

Conclusions: In anesthetized male pigs, S2 ES induces a robust motility response in the distal colon via the central network while in the anal canal via efferent pathways.