Neurogastroenterology and Motility最新文献

Background: Functional lumen imaging probe (FLIP) utility is established in treatment-naïve achalasia but less clear following lower esophageal sphincter (LES) directed therapy.

Methods: Achalasia patients with LES directed therapy across three tertiary care centers between 2017 and 2024 with post-treatment FLIP and timed barium esophagram (TBE) were retrospectively identified. Reduced esophagogastric junction (EGJ) opening was defined by distensibility index (DI) < 2 mm²/mmHg and diameter < 12 mm. Abnormal emptying on TBE was defined as column height ≥ 5 cm at 5 min and/or retained tablet. Eckardt scores ≤ 3 defined clinical response.

Key results: The study included 222 patients (46% peroral endoscopic myotomy, 46% laparoscopic Heller myotomy, 8% pneumatic dilation) with a median of 1.4 years to post-treatment TBE/FLIP. Abnormal emptying on TBE was associated with a narrower median EGJ diameter (13.2 vs. 14.8 mm, p = 0.008), a greater frequency of EGJ diameter < 12 mm (36% vs. 21%, p = 0.012), and a smaller change in EGJ diameter (+4.6 vs. +8.6 mm, p = 0.002). Abnormal emptying on TBE occurred more frequently in patients with EGJ DI < 2 mm²/mmHg (8.5% vs. 2.6%, p = 0.052), but was not associated with median EGJ DI (4.5 vs. 5.1 mm²/mmHg, p = 0.29) nor median change in EGJ DI (+2.9 vs. +3.9 mm²/mmHg, p = 0.25). Patients with reduced EGJ DI or EGJ diameter more often had abnormal TBE (37% vs. 22%, p = 0.012). Only the change in DI (+3.8 vs. +1.5 mm²/mmHg, p = 0.012) and diameter (+8.2 vs. +1.6 mm, p = 0.002) on FLIP was associated with a clinical response based on Eckardt ≤ 3.

Conclusions and inferences: FLIP following achalasia therapy generally correlates with TBE, although discrepant findings are not uncommon. In particular, FLIP EGJ-diameter has a strong association with esophageal emptying on TBE. Both TBE and FLIP have limited association with clinical response based on Eckardt, with change in DI and diameter on FLIP most strongly associated. Consequently, FLIP as part of multimodal assessment appears useful in the longitudinal follow-up of treated achalasia.

Background: Gastroparesis is common in patients with diabetes. However, treatment options for diabetic gastroparesis are limited. Transcutaneous electrical acustimulation (TEA), a noninvasive method of delivering electrical stimulation via surface electrodes placed at certain acupuncture points that are in the vicinity of peripheral nerves, has been reported to exert therapeutic effects in patients with gastroesophageal reflux, functional dyspepsia, and constipation. The aim of this study was to explore the therapeutic potential of TEA for diabetic gastroparesis.

Methods: Eighteen patients with diabetes were enrolled in a single-center, placebo-controlled, randomized and crossover trial with TEA and sham-TEA. TEA was performed twice daily after lunch and dinner via acupoints, ST36 (below the kneecap in the vicinity of the peroneal, sciatic, and tibial nerves) and PC6 (wrist above the median nerve) for 4 weeks. A set of parameters previously reported to improve gastrointestinal motility was used for both TEA and sham-TEA (delivered via sham-points). The gastroparesis cardinal symptom index was used to assess symptoms. The electrogastrogram (EGG) was used to assess gastric pace-making activity (slow waves).

Key results: The TEA treatment improved each of the five major gastroparesis symptoms in comparison to baseline: nausea reduced by 29.7% (p = 0.005), retching by 31.1% (p = 0.006), vomiting by 39.3% (p = 0.005), abdominal fullness by 21.4% (p = 0.005), and bloating by 20.6% (p = 0.006). There was also a significant improvement in the "pain interfering with activity" score with the 4-week TEA treatment in comparison to baseline (p = 0.046). TEA improved gastric pace-making activity, reflected as a significant increase in the percentage of normal gastric slow waves in the postprandial state (69.5% ± 12.1% vs. 77.4% ± 16.5%, p = 0.039). Concurrently, TEA resulted in a trend of postprandial increase in vagal activity.

Conclusions and inferences: TEA at acupuncture points ST36 and PC6 with appropriate parameters is effective in treating the major gastrointestinal symptoms in patients with diabetic gastroparesis. Further pivotal studies are warranted to determine its clinical efficacies.

Purpose: This work delves into the critical role of the human gut microbiome in health and disease, emphasizing its influence on a range of physiological processes and its connection to conditions such as irritable bowel syndrome (IBS). The microbiome is made up of a very large and complicated group of microorganisms that have big effects on metabolic and immune functions. This makes it an interesting area for researching new ways to diagnose and treat diseases. Analyzing this data introduces substantial challenges due to its high dimensionality, intricate microbial interactions, and significant inter-individual variability.

Methods: The above factors demand the application of sophisticated machine learning techniques that can efficiently manage and interpret such complex, high-dimensional data. The XGBoost, RandomForest, Logistic Regression, LightGBM, and a deep neural network (DNN) are specifically tailored for this work. Each model's implementation is meticulously designed to extract meaningful patterns from the microbiome data with the required preprocessing by focusing on achieving high accuracy, sensitivity, and specificity in disease classification. The models are implemented using Python's libraries and are evaluated through rigorous cross-validation on a comprehensive dataset of microbiome profiles to ensure robustness and reliability.

Results: A comparison study is done to find out what each model does well and what it does not do so well. The DNN's dense layered neurocomputing pattern recognition skills make it very good at dealing with the complexity of microbiome data, resulting in an accuracy of 92.79%.

Conclusion: This study not only adds to our knowledge of how the microbiome affects health, but it also pushes the limits of diagnostic methods. By using cutting-edge deep machine learning innovations in biomedical research, we may be able to improve health outcomes around the world.

Background: Irritable bowel syndrome (IBS) is a gut-brain interaction disorder that significantly impacts quality of life, with symptoms influenced by stress, anxiety, dietary habits, and gut microbiota imbalances. Alexithymia, characterized by difficulties in identifying and expressing emotions, may exacerbate IBS symptoms by impairing stress management and illness perception. Additionally, poor adaptation to chronic illness can increase psychological burden and worsen symptom severity.

Methods: This cross-sectional study examined 148 IBS patients diagnosed using Rome IV criteria at a gastroenterology outpatient clinic. Data were collected through validated scales, including the IBS Symptom Severity Score (IBS-SSS), Twenty-Item Toronto Alexithymia Scale (TAS-20), and Chronic Disease Adaptation Assessment Scale (CDAAS). Correlation and multiple regression analyses were conducted to identify key predictors of symptom severity.

Results: IBS severity was notably high (mean IBS-SSS = 380.1 ± 61.5), with low income (B = 32.337, p = 0.002) and high alexithymia levels (B = 0.991, p = 0.045) emerging as strong predictors of increased symptom burden. Marital status also showed a notable association (B = 22.005, p = 0.085). While overall disease adaptation (CDAAS) was not directly linked to symptom severity, poor physiological adaptation correlated negatively with IBS symptoms, suggesting a critical role in disease perception. A significant inverse relationship was found between meal frequency and symptom severity (r = -0.170, p = 0.039), highlighting the impact of dietary habits on symptom control. The regression model explained 14.9% of variance (adjusted R² = 0.081).

Conclusion: IBS symptom severity is partially influenced by socioeconomic status, emotional regulation, and dietary patterns. These findings underscore the need for a multidisciplinary treatment approach integrating dietary modifications, psychological interventions, and tailored patient support to enhance disease management and improve patient outcomes.

Background: Microbial overgrowth (MO) in the small intestine can cause gastrointestinal symptoms and may arise from stasis, such as dysmotility. Microtypes of MO include small intestinal bacterial overgrowth (SIBO) and intestinal methanogen overgrowth (IMO). Dyssynergic defecation (DD) is associated with constipation and slow colonic transit (STC). Our aim was to assess the relationship between DD and MO.

Methods: We retrospectively identified patients who underwent both anorectal manometry (ARM) and balloon expulsion testing (BET) for DD, and MO testing using either small intestinal aspirate culture or breath testing. SIBO was analyzed using two culture thresholds: ≥ 10⁵ CFU/mL and ≥ 10³ CFU/mL. Chi-square tests compared positive vs. negative results.

Key results: 436 patients underwent culture of SB aspirates. At the ≥ 10⁵ CFU/mL threshold, 41.7% were diagnosed with SIBO, and 87.4% at ≥ 10³ CFU/mL. At ≥ 10⁵ CFU/mL, percent anal relaxation was significantly lower in SIBO-positive patients. SIBO patients were more likely to have reduced anal relaxation (p = 0.032), but no other ARM parameters or BET > 60 s. At ≥ 10³ CFU/mL, a more negative recto-anal pressure differential (RAPD) was observed, along with a combination of RAPD < -45 mmHg and resting anal pressure > 90 mmHg. 637 patients underwent breath testing for MO, with 174 positive results, predominantly showing IMO (73%). In this group, BET was significantly longer, and anal relaxation was significantly lower. SIBO at ≥ 10³ CFU/mL was more prevalent in DD than STC (85.5% vs. 64.7%, p = 0.002). IMO was more common in DD than STC (p = 0.021).

Conclusion/inferences: DD may be a risk factor for MO, often with evidence of methanogenesis.

Background: Current clinical guidelines for chronic constipation offer limited dietary recommendations. The aim of this project was to develop the first comprehensive evidence-based dietary guidelines for the management of chronic constipation in adults.

Methods: Four systematic reviews and meta-analyses were performed to identify eligible randomized controlled trials (RCTs). The findings generated from the meta-analyses were then used to develop guideline statements using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach and a Delphi consensus survey among a multidisciplinary expert Guideline Steering Committee. Recommendation statements were produced for treatment response, stool output, gut symptoms, adverse events, and quality of life, and only based on the findings where ≥ 2 RCTs contributed to the meta-analysis. The strength of recommendation was assessed using the GRADE approach. Consensus voting among the Guideline Steering Committee was performed using a modified Delphi survey approach.

Results: The four systematic reviews included a total of 75 RCTs. Fifty-nine dietary recommendation statements were generated and accepted through the Delphi survey. For dietary supplements, 15 recommendation statements relate to fiber supplements, 20 relate to probiotics, two to synbiotics, five to magnesium oxide, two to senna, and three to kiwifruit supplements. For foods, three recommendation statements related to kiwifruits, two to prunes, and two to rye bread. For drinks, five recommendation statements related to high mineral-containing water. No recommendations were made for whole diet approaches due to lack of evidence. Twelve statements had a very low level of evidence, 39 had a low level of evidence, and eight had moderate evidence. Twenty-seven statements were strong recommendations, and 32 were qualified recommendations.

Conclusions: These are the first comprehensive evidence-based dietary guidelines for the management of constipation based upon a robust systematic review and GRADE processes. Recommendations were made for dietary supplements, foods, and drinks that have never been previously included in clinical guidelines, and can now be rapidly implemented into clinical practice, thereby improving clinical care and patient outcomes.

Background: During the COVID-19 pandemic, the prevalence of disorders of gut-brain interaction (DGBI) in the US increased. The pandemic also led to health inequities among racial and ethnic minorities. Here, we conducted monthly national surveys during the pandemic to examine the association between race/ethnicity and pandemic-onset DGBI.

Methods: From March 2021 to May 2022, we recruited a nationally representative sample of adults in the US to complete an online survey with Rome IV questionnaires (9 gastroduodenal and bowel DGBI) along with demographic and comorbidity questions. Participants with a DGBI were asked whether their cardinal symptoms started before or after the COVID-19 pandemic began in the US (March 2020). Our primary outcome was the prevalence of pandemic-onset DGBI. Multivariable logistic regression models identified factors associated with pandemic-onset DGBI. We also tested for an interaction between race/ethnicity and COVID-19 positivity to assess whether the relationship between pandemic-onset DGBI and race/ethnicity varied by COVID-19 status.

Results: Among 71,547 respondents, 26,103 (36.5%) had ≥ 1 DGBI. Across most DGBI, non-Hispanic Blacks and Hispanics had higher odds for pandemic-onset DGBI (e.g., irritable bowel syndrome, functional dyspepsia, functional bloating) versus non-Hispanic Whites. When including interaction terms between race/ethnicity and COVID-19 positivity, most were not significant (p > 0.05), showing that the relationship between pandemic-onset DGBIs and race/ethnicity did not vary by COVID-19 status.

Conclusions: In this US survey, racial/ethnic minorities had higher odds of reporting pandemic-onset DGBI. This association was independent of COVID-19 positivity, suggesting that differences in pandemic-onset DGBI among groups may be related to psychosocial challenges faced by racial/ethnic minorities rather than direct effects of SARS-CoV-2.

Background: During pre-bariatric surgery evaluation, we routinely perform objective testing for GERD (endoscopy, pH monitoring if no reflux esophagitis found) with high-resolution manometry (HRM) and functional lumen imaging probe (FLIP) to evaluate esophageal motility. In this study, we aimed to identify differences in FLIP metrics between obese patients with and without GERD.

Methods: We reviewed our clinical database of obese patients evaluated for bariatric surgery, including surgery-naïve patients and patients who had sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) that resulted in inadequate weight loss. We recorded GERD symptoms, HRM findings, and FLIP metrics (EGJ-diameter, distensibility index, and contractile response patterns). Patients with reflux esophagitis or acid exposure time (AET) > 6% were considered GERD+; those with AET ≤ 6% were deemed GERD.

Key results: We included 160 patients (mean age 50.2 ± 12.4 years; 79% women; 66 surgery-naïve) (29 GERD-, 37 GERD+), 70 SG (20 GERD-, 50 GERD+), 24 RYGB (16 GERD-, 8 GERD+). FLIP abnormalities were frequent, including reduced EGJ opening (REO) (12.1% surgery-naïve, 14.3% SG, 12.5% RYGB) and abnormal contractile response (59.1% surgery-naïve, 71.4% SG, 62.5% RYGB). FLIP differences were found between GERD+ and GERD- patients: REO (8.0% vs. 30.0%, p = 0.02) and BCR (2.0% vs. 15.0%, p = 0.02) were both less frequent in GERD+ than in GERD- SG patients. SRCR was more frequent in GERD- than in GERD+ surgery-naïve patients (31.0% vs. 5.4%, p = 0.01).

Conclusions: While FLIP differences between GERD- and GERD+ patients exist, there were no FLIP metrics that clearly predicted GERD in obese patients either before or after bariatric surgery.

Background: Neurogenic fecal incontinence (NFI) is a disorder of anal dysfunction caused by nerve damage. Electroacupuncture (EA), grounded in Traditional Chinese Medicine (TCM) theory, has demonstrated efficacy in treating various degenerative disorders and is extensively utilized in the clinical management of neurogenic FI. The proliferation and differentiation of muscle satellite cells (SCs) are crucial in the onset and progression of this condition. However, the specific mechanism of electroacupuncture in treating neurogenic fecal incontinence is not yet clear. This study sought to determine whether EA could enhance anal function in rats with neurogenic FI and to elucidate its mechanisms of action.

Methods: We observed the effect of electroacupuncture on anorectal function in rats with neurogenic fecal incontinence and its mechanism of action.

Key results: The morphology and arrangement of anal sphincter muscle fibers were altered due to pudendal nerve injury. The expression levels of two atrophy markers, Muscle-specific RING finger protein 1 (MuRF-1) and Atrogin-1, were elevated in the anal sphincter muscles, and shifts were seen from slow-twitch to fast-twitch muscle fibers. Post EA treatment, the expression levels of atrophy markers were reversed; the proportion of slow-twitch fibers in the muscles increased, and the expressions of Pax3 and Myod1, which had decreased 3 weeks post-injury, significantly increased and gradually normalized.

Conclusions & inferences: These results indicate that EA effectively ameliorates anal function in rats with neurogenic FI, primarily through mechanisms that involve the activation of muscle SCs.

Background: The circadian rhythm regulates gastrointestinal motility. In humans and preclinical models, such as rodents, whole gut transit (WGT) is slower during the rest phase compared to the active phase. Investigators typically study GI transit in rodents during the day, which is their rest phase, rather than during the night, which is their active phase. A circadian rhythm reversal in which mice are in a dark room during the working day (reverse light) allows studies on nocturnal animals during their active phase and has been previously shown to reduce WGT time. GI motility is often disrupted in individuals with disorders of gut-brain interaction (DGBI), which are female predominant. However, the effect of circadian rhythm on regional transit and sex dependence of the differences is not known, as most motility studies looking at circadian rhythm reversal are done in male mice.

Methods: We tested C57BL/6 wild-type male and female mice in rest (12 h of light during the day) and active (reverse cycle for 2 weeks: 12 h of dark during the day) phases. We noted female estrous cycle by visual inspection. We performed carmine WGT by monitoring time-lapse videos of pellet production. We performed fluorescence imaging of excised intestines 30 min after gavage to assess percent fluorescence for each GI region and then examined small intestinal transit (SIT) by measuring geometric center and leading edge. For colonic transit, we monitored bead expulsion time from distal colon to anus.

Key results: Compared to rest phase, in the active phase, like male mice, female mice had (1) faster WGT, (2) increased frequency of pellet expulsion in the first 3 h of transit, (3) and greater total pellet production. Both male and female mice in their active phase exhibited (4) more contrast emptied from the stomach and they had (5) further leading edge of fluorescence and (6) geometric center, in SIT, and (7) faster colonic bead expulsion times. There were no significant sex differences in the active phase of WGT. In SIT, male mice had further leading edge in the rest phase than female mice, but this difference was not seen in the active phase, and in colonic transit, male mice in both the active and rest phases had faster bead expulsion than female mice.

Conclusions: Mice in the active phase have faster regional transit in small and large bowel than mice in the rest phase that collectively contributes to faster WGT times in the active phase of both male and female mice. These findings highlight the importance of circadian biology in sex-dependent rodent GI transit.