Motility Disorders Research Articles

Diagnostic approach to patients with suspected motility disorders: one size does not fit all.

Dysphagia and retrosternal chest pain are considered typical manifestations of major esophageal motility disorders (mEMD). High-resolution manometry (HRM) is the gold standard for mEMD diagnosis, while endoscopy and barium swallow are ancillary tools. We aimed to investigate the frequency of mEMD among patients referred for HRM with typical compared to non-typical symptoms. We also evaluated endoscopic and barium swallow data from patients with mEMD who underwent HRM. We retrospectively collected epidemiological, endoscopic, barium swallow, and HRM data from 302 patients. Atypical symptoms were considered to be heartburn, regurgitation, globus, oropharyngeal dysphagia, and epigastric pain. The main referral symptoms were: esophageal dysphagia, 58.3%; chest pain, 13.7%; heartburn, 8.9%; regurgitation, 8.3%; and globus/oropharyngeal dysphagia/epigastric pain, 10.8%. A diagnosis of mEMD was more common when typical symptoms existed (69.9% vs. 15.4%, P<0.001). The majority of patients with mEMD in HRM, independently of their symptoms, had an abnormal barium study (typical: 94.8% vs. non-typical: 100%, P=0.633), while compatible endoscopic data tended to be observed more frequently among patients with typical symptoms (69.1% vs. 40%, P=0.057). An HRM diagnosis of mEMD among patients with compatible findings from either barium swallow or endoscopic examination was statistically more frequent among patients with typical symptoms (92.4% vs. 52.6%, P<0.001). More than half of patients referred for HRM will be diagnosed with mEMD, at a higher rate when typical symptoms are reported. A lack of compatible endoscopic and barium swallow findings, in the absence of typical symptoms, makes the diagnosis of mEMD almost impossible.

The bitter flavor of Banxia Xiexin decoction activates TAS2R38 to ameliorate low-grade inflammation in the duodenum of mice with functional dyspepsia.

Banxia Xiexin Decoction (BXD) is a traditional herbal formulation with a bitter flavor that has a long-standing history of use in Asia for treating functional dyspepsia (FD). In traditional Chinese medicine, the bitter flavor is believed to play a critical role in the therapeutic activity of BXD. The ethnopharmacological properties of bitter plant extracts are closely associated with their anti-inflammatory effects, which may contribute to their efficacy in FD. However, the specific mechanisms remain unknown. The objective of this study is to uncover the bitter active compounds of BXD and their effects in the treatment of FD. The chemical compounds of BXD were identified using HPLC-Q-Exactive-MS. Active compounds in BXD were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database, and bitter active compounds were further identified using BitterDB and PlantMolecularTasteDB. Molecular docking was employed to identify potential targets of these bitter active compounds, and their activation was validated through flow cytometry analysis of Ca2+. Subsequently, a mouse model of FD was established, and our hypothesis was further validated using enzyme linked immunosorbent assay, immunohistochemistry, immunofluorescence, and western blotting. Through HPLC-Q-Exactive-MS analysis, TCMSP, BitterDB, and PlantMolecularTasteDB database, a total of 11 bitter active compounds in BXD were identified: Baicalein, Baicalin, Berberine, Coptisine, Formononetin, Isorhamnetin, Kaempferol, Naringenin, Palmatine, Quercetin, and Wogonin. Molecular docking results indicated that these active compounds exhibited strong affinity for TAS2R38, with Berberine showing the highest scoring. Flow cytometry analysis of Ca2+ revealed that both Berberine and BXD elevated intracellular calcium concentrations, although this effect was partially antagonized by the TAS2R38 inhibitor probenecid. In vivo experiments demonstrated that BXD effectively improved eosinophil infiltration in the duodenum of FD mice, downregulated the expression of inflammatory factors IL-1β, IL-5, and TNF-α, inhibition of NF-κB signaling pathway activation, alleviated damage to the duodenal mucosal barrier, and reversed gastrointestinal motility disorders, with the therapeutic effect enhancing with increasing doses of BXD. However, this therapeutic effect was partially inhibited following probenecid intervention. BXD contains numerous bitter active compounds that play a significant role in regulating inflammatory activity in the duodenum of FD through the activation of TAS2R38. This finding unveils, for the first time, the ethnopharmacological activity of bitter plant taste agents in anti-inflammatory effects, providing new insights for the treatment and drug development of FD.

The assessment of gastrointestinal transit by the Atmo Capsule: A comparison with the SmartPill Capsule.

Wireless motility capsules (WMCs) can be used to assess gastrointestinal transit time to facilitate diagnosis and treatment of motility disorders. The Atmo Capsule is a novel WMC that measures gases (H2, CO2, O2) and temperature. We aimed to compare and evaluate the performance characteristics of the Atmo Capsule and the SmartPill Capsule (discontinued reference standard WMC) for measurement of gastric emptying time (GET) and colonic transit time (CTT) , in patients with confirmed or suspected disordered gastrointestinal transit. Patients with symptoms indicative of an upper and/or lower gastrointestinal motility disorder ingested the two WMCs in a random order. Gastrointestinal transit times were assessed using Spearman correlation and Bland-Altman analysis. Device agreement was assessed for delayed GET (≥ 5 hours) and CTT (≥ 59 hours). There were 213 participants from 12 sites, yielding 177 paired GET and 147 paired CTT measurements. The measurements for GET and CTT with the Atmo Capsule and SmartPill Capsule were strongly correlated (GET, R=0.73, P<0.01; CTT, R=0.69, P<0.01) and their observed biases were within 10% of the delayed transit margin. Both delayed GET (68/177) and CTT (56/147) were identified in 38% of participants with 84% agreement for identification of both delayed GET (sensitivity 78%, specificity 86%) and CTT (sensitivity 67%, specificity 93%). No serious adverse device effects were reported. The performance characteristics of the Atmo capsule for measurements of GET and CTT, were equivalent to the reference standard WMC with a strong correlation and good device agreement. These results demonstrate that the Atmo Capsule is a valid method for evaluating gastrointestinal transit.

Duodenogastric Reflux in Health and Disease: Insights from a Computational Fluid Dynamics Model of the Stomach.

The stomach is responsible for physically and chemically processing the ingested meal before controlled emptying into the duodenum through the pyloric sphincter. An incompetent pylorus allows reflux from the duodenum back into the stomach, and if the amount of reflux is large enough, it could alter the low pH environment of the stomach and erode the mucosal lining of the lumen. In some cases, the regurgitated contents can also reach the esophagus leading to additional complications. In this work, "StomachSim", an in-silico model of the fluid dynamics of the stomach, is used to study the mechanism of duodenogastric reflux. The effects of variations in food properties and motility disorders on reflux are investigated. The simulations show that the primary driver of reflux is the relaxation of the antrum after a stomach contraction terminates near the pylorus. The region of the stomach walls exposed to the regurgitated contents depends significantly on the density of the stomach contents. For stomach contents of higher viscosity, the increased pressure required to maintain gastric emptying reduces the amount of duodenogastric reflux. Concomitant stomach motility disorders that weaken the relaxation of the walls also affect the amount of reflux. The study illustrates the utility of in-silico models in analyzing the factors at play in gastrointestinal diseases.

Peroral Endoscopic myotomy (POEM) in pediatric achalasia: a retrospective cohort on institutional experience and quality of life

BackgroundAchalasia is a rare esophageal motility disorder with an estimated annual incidence of 1–5/100.000 and a mean age at diagnosis > 50 years of age. Only a fraction of the patients has an onset during childhood (estimated incidence of 0.1–0.18/ 100.000 children per year). No curative treatment is currently available. Peroral Endoscopic Myotomy (POEM) is a widely accepted treatment option to improve symptoms in adults. Studies evaluating safety and efficacy of POEM in children are scarce and no data exist regarding the quality of life in patients after POEM.MethodsWe evaluated the effectiveness and safety of POEM in a cohort of children that was treated for achalasia and we prospectively evaluated their quality of life. We compared the results to a previous cohort evaluating Pneumatic Dilation (PD) and Laparoscopic Heller’s Myotomy (LHM) in children with achalasia.ResultsThirty-three achalasia patients (age at time of POEM 14.1(± 2.5) years, 54.5% female) were included. Twenty-nine (87.8%) percent had received previous treatment (PD (n = 20); LHM (n = 1); PD + LHM (n = 7); PD + Botox (n = 1). POEM was technically successful in all patients and no major complications occurred. Mean follow-up duration was 33 (± 25) months. Twenty three (70%) patients did not need retreatment after POEM during the follow up period. Quality of life after POEM did not differ from the population norms. Patients with an Eckardt score > 3 had a significantly worse general (Kidscreen-52: physical score 44.7 vs. 52.4; p = 0.011; mental score: 42.5 vs. 51.3; p = 0.038) and disease specific (35 vs. 16; p = 0.017) quality of life compared to those with an Eckardt ≤ 3. The SF-36 mental health component score was significantly lower (44.2 vs. 53.1; p = 0.036) in patients treated with POEM compared to those treated with PD and LHM. These lower scores could be related to a selection bias, as more severe patients received POEM, and other influences such as the Corona pandemic. However, the overall, quality of life after POEM was not significantly different to PD and LHM.ConclusionPOEM is an effective and safe treatment for achalasia in children. Quality of life after POEM is comparable to the results obtained after PD and Heller.

P0229 Evaluation of anorectal function and structure in patients with perianal Crohn's disease with a novel 3-D high-definition anorectal manometry technology

Abstract Background Crohn’s disease (CD) is a type of inflammatory bowel disease (IBD) that can have perianal involvement with a fistulizing phenotype (PFCD) and could affect anal sphincter integrity, leading to morbidity and reduced quality of life (QoL) due to fecal incontinence (FI) and rectal pain. High-definition 3D anorectal manometry (HD-ARM) is a novel technique that allows volumetric imaging of the anal canal through 2D and 3D images, enabling visualization of morphology and identification of pressure defects caused by lesions in the sphincter complex. There are no studies in patients with IBD with this modality of manometry. Our aim is to determine the functional and structural abnormalities of the sphincter complex using HD-ARM in patients with CD with and without PFCD and to correlate these findings with magnetic resonance imaging (MRI) results. Methods This is a prospective, longitudinal cohort study of anorectal function using HD-ARM and rectal sensitivity using rectal barostat in patients with CD from our IBD unit. Patients were recruited during follow-up visits regardless of whether or not they reported anorectal symptoms. Findings were correlated with clinical activity of CD (Harvey Bradshaw index), PFCD activity index (PDAI), FI severity index (Jorge-Wexner and St. Marks scores), QoL scores (IBDQ-9 for IBD and FIQLS for FI), and perineal MRI to confirm anatomical abnormalities. Results A total of 19 patients were recruited from December 2023 to September 2024, 68.4% of whom were female. Among patients with PFCD (68.4% of the total), 84.6% had undergone some form of anorectal surgery. Only two patients from the total cohort (10.5%) had normal HD-ARM results. The main manometric diagnoses were: rectal hypersensitivity (36.8%), rectal hyposensitivity (31.6%), internal anal sphincter insufficiency (weakness) (21.1%), incomplete evacuation maneuvers (21.1%), and dyssynergic defecation (15.8%), with no significant differences between the groups with and without PFCD. In 90% of patients with PFCD, MRI findings correlated with the presence or absence of pressure defects on the HD-ARM. Patients with pressure defects on the HD-ARM had higher FI scores on the Jorge-Wexner (7.5 vs. 3.3) and St. Marks (9 vs. 5) scores, although this difference did not reach statistical significance (p=0.07). No differences in quality of life or luminal/perianal disease activity index were found in association with manometric alterations. Conclusion Anorectal sphincter function abnormalities are common in patients with CD, with or without concomitant perianal disease. HD-ARM is a useful tool to correlate functional anorectal abnormalities with anatomic abnormalities on perineal MRI. References Eglinton TW, Barclay ML, Gearry RB, et al. The spectrum of perianal Crohn’s disease in apopulation-based cohort. Dis Colon Rectum 2012;55:773–7. Felt-Bersma, R.J.F., Vlietstra, M.S., Vollebregt, P.F. et al. 3D high-resolution anorectal manometry in patients with perianal fistulas: comparison with 3D-anal ultrasound. BMC Gastroenterol 18, 44 (2018) R Costache, A Dimitriu, A Les, C Gheorghe, P027 Anorectal Motility Disorders in Inflammatory Bowel Disease patients, Journal of Crohn's and Colitis, Volume 17, Issue Supplement_1, February 2023, Page i197 De Codes LMG, de Jesus ACC, de Codes JJG, Ferreira RF, da Silva Beda Sacramento C, da Cruz IDM, de Castro Ribeiro Fidelis F, de Carvalho AL, Motta MP, de Oliveira Alves C, Netto EM, Santana GO. Anorectal function and clinical characteristics associated with fecal incontinence in patients with Crohn's disease. J Crohns Colitis. 2023 Mar 23:jjad048

P0386 Prevalence and Impact of Anorectal Disorders in IBD: Insights from a Romanian Tertiary Gastroenterology Center

Abstract Background Anorectal motility disorders profoundly affect the quality of life in patients with quiescent inflammatory bowel disease (IBD). Although faecal incontinence (FI) has a reported prevalence of up to 74%, its true extent is likely underestimated due to the stigma surrounding the condition. Fear of FI and challenges in accessing toilets remain significant concerns. This study evaluates the prevalence of these issues in Romanian tertiary care patients using the validated questionnaire International Consultation on Incontinence Questionnaire for Bowel Incontinence – IBD (ICIQ-IBD). Methods We surveyed 65 IBD patients aged over 18, admitted to our center, who were in remission but had previously experienced moderate to severe disease. Using the ICIQ-IBD questionnaire, we collected data on faecal incontinence, soiling, anal dyskinesia, their impact on quality of life, and demographic information. The analysis was conducted using Excel and Minitab. Results Of the 65 patients included in the study, 69% were male, with a median age of 40.82 ± 12.10 years. The majority were diagnosed with Crohn’s disease (65% CD, 35% UC). During remission, 22% of patients reported the need to rush to the toilet “always” or “most of the time,” compared to 40% during relapse, with a significant difference between disease phases (p = 0.02) but no differences based on gender or diagnosis. In relapse, 68% of patients had less than one minute to reach a toilet, compared to 32% in remission (p = 0.00). Soiling was reported by 49% of patients during active disease and 25% in remission (p = 0.004). Difficulty controlling liquid stools affected 62% of patients in relapse and 55% in remission, with no significant difference between disease states (p = 0.417). Emotional impact was reported by 72% of patients in relapse and 15% in remission, highlighting the psychosocial burden of bowel dysfunction in IBD. Conclusion Anorectal disorders significantly affect IBD patients’ quality of life, even during remission. Key symptoms, such as soiling and urgency, were more prevalent during relapse and strongly linked to emotional distress. These findings underscore the need for targeted management of anorectal symptoms in IBD care. References Norton, Christine et al. “Faecal incontinence in inflammatory bowel disease: associations and effect on quality of life.” Journal of Crohn’s &amp; colitis vol. 7,8 (2013): e302-11. doi:10.1016/j.crohns.2012.11.004 Dibley, Lesley et al. “Development and initial validation of a disease-specific bowel continence questionnaire for inflammatory bowel disease patients: the ICIQ-IBD.” European journal of gastroenterology &amp; hepatology vol. 28,2 (2016): 233-9. doi:10.1097/MEG.0000000000000513

Predictive model for estimating total acid exposure time in patients with esophageal hypomotility disorders.

The latest Chicago Classification of esophageal motility disorders categorizes esophageal hypomotility disorders (EHD) into absent contractility (AC) and ineffective esophageal motility (IEM). While these disorders are commonly associated with gastroesophageal reflux disease (GERD), they are not pathognomonic. To improve diagnostic accuracy, provocative maneuvers during high-resolution esophageal manometry (HRM) -such as multiple rapid swallows (MRS) and single solid swallows (SSS) -have been introduced.

Gastrointestinal motility modulation efficacy-related chemical marker findings and QAMS-based quality control of Agastache rugosa.

Agastache rugosa (AR), a traditional edible and medicinal herb, is often used for treating gastrointestinal (GI) motility disorder. But little effort has been done on its gastrointestinal motility modulation (GMM) efficacy-related components and quality control of AR. In this study, a novel strategy was proposed to find GMM efficacy-related chemical markers for the quality control of AR. Firstly, network pharmacology and serum pharmacochemistry were applied to predict potential GMM efficacy-related marker components. Secondly, the GMM efficacy-related marker components were verified through literature matching, target isolation/identification and activity evaluation. Lastly, a quantitative analysis of multiple components by a single marker (QAMS)-based method for simultaneous quantification of marker components was established and validated by HPLC-DAD. The results showed that nine components in AR were screened as potential GMM related components, five of which (rosmarinic acid, tilianin, apigenin, acacetin, and cirsimaritin) were matched by literatures, and four (acacetin-7-O-(6''-O-malonyl)-β-D-glucopyranoside, agastachoside, acacetin-7-O-(2''-O-acetyl-6''-O-malonyl)-β-D-glucopyranoside, and isoagastachoside) were chemically identified and newly evaluated on zebrafish model. The nine components were used as marker compounds to develop an effective QAMS-based method for the quantitative evaluation of 26 batches of commercial AR samples.

Single Versus Dual Therapy for Diabetic Gastroparesis

Gastroparesis is a disorder of gastric motility hallmarked by nausea, vomiting and early satiety. While dietary and medical therapy are the mainstay of treatment, surgery has been useful to palliate symptoms. Two long-used first line surgical therapies for gastroparesis are gastric electrical stimulation and pyloric procedures (including pyloroplasty and pyloromyotomy). This manuscript will focus on the use of these surgical modalities, both separately and in combination, to treat refractory gastroparesis symptoms in patients with diabetes.

Artificial intelligence as a transforming factor in motility disorders–automatic detection of motility patterns in high-resolution anorectal manometry

High-resolution anorectal manometry (HR-ARM) is the gold standard for anorectal functional disorders’ evaluation, despite being limited by its accessibility and complex data analysis. The London Protocol and Classification were developed to standardize anorectal motility patterns classification. This proof-of-concept study aims to develop and validate an artificial intelligence model for identification and differentiation of disorders of anal tone and contractility in HR-ARM. A dataset of 701 HR-ARM exams from a tertiary center, classified according to London Classification, was used to develop and test multiple machine learning (ML) algorithms. The exams were divided in a training and testing dataset with a 80/20% ratio. The testing dataset was used for models’ evaluation through its accuracy, sensitivity, specificity, positive and negative predictive values and area under the receiving-operating characteristic curve. LGBM Classifier had the best performance, with an accuracy of 87.0% for identifying disorders of anal tone and contractility. Different ML models excelled in distinguishing specific disorders of anal tone and contractility, with accuracy over 90.0%. This is the first worldwide study proving the accuracy of a ML model for differentiation of motility patterns in HR-ARM, demonstrating the value of artificial intelligence models in optimizing HR-ARM availability while reducing interobserver variability and increasing accuracy.

Pulmonary Aspiration Syndromes: An Imaging-based Review.

The term "aspiration" describes lung injury that results from unintentional passage of contents other than air into the lungs and bronchial tree, commonly from the gastrointestinal and upper respiratory tracts. Only a small proportion of aspiration-related events are symptomatic, especially in predisposed individuals such as patients with diminished consciousness, impaired swallowing, oesophageal motility disorders, and reflux disease. Aspiration-related syndromes can be classified based on the onset of presentation, composition of the aspirated substance, and anatomic site of injury. When considering the injury site, the aspirated material can either obstruct the airways, thereby presenting with obstructive features (eg, atelectasis on radiographs); it can alternatively affect the lung parenchyma. Lung injury due to aspiration of noxious agents such as acid or lipids is termed chemical aspiration pneumonitis. The aspirated contents can alternatively lead to lung parenchymal infection when the contents are infected, which is termed aspiration pneumonia. We have reviewed the imaging manifestations of various entities related to aspiration and have classified the abnormalities based on the site of injury and the nature of the culprit agent. Differences between "aspiration pneumonitis" and "aspiration pneumonia" are also explored. This is followed by an illustration of a few specific situations related to aspiration in pediatric and adult patients.

Effectiveness and safety of full-thickness versus circular muscle myotomy in peroral endoscopic myotomy: a retrospective single-center analysis of 152 patients.

Achalasia is a primary esophageal motility disorder, which shows impaired relaxation of the lower esophageal sphincter (LES) and the absence of peristalsis, leading to dysphagia, weight loss, and chest pain. In recent years, peroral endoscopic myotomy (POEM) has become a popular method for treating achalasia. However, the effectiveness and safety of full-thickness myotomy (FTM) versus circular muscle myotomy (CMM) in POEM require further investigation. This retrospective single-center analysis studied 152 patients who underwent POEM surgery at the General Hospital of the Western Theater Command from May 2014 to May 2023. Patients were divided into two groups based on the depth of myotomy: the FTM group and the CMM group. Parameters such as surgical success rate, procedure time, and myotomy length were evaluated, and treatment efficacy was assessed based on the Eckardt score. Postoperative complications and efficacy were also monitored. Technical success was achieved in both groups, with shorter procedure times in the FTM group (P < 0.05). There were no significant differences in postoperative Eckardt scores and symptom improvement between the FTM and CMM groups. The incidence of adverse events was similar in both groups. The incidence of gastroesophageal reflux disease (GERD) seemed to be higher in the FTM group, although this difference was not statistically significant (P = 0.051). For patients with achalasia, there were no significant differences in short-to-medium-term treatment efficacy and safety between FTM and CMM in POEM. Although FTM significantly reduced procedure time, it may lead to a higher incidence of GERD. More cases are needed in the future to explore the more appropriate myotomy for different achalasia subtypes.

Modern Experience in Pharmacotherapy of Irritable Bowel Syndrome in Children

This review examines modern approaches to the diagnosis and treatment of irritable bowel syndrome (IBS) in children, one of the most common functional disorders of the gastrointestinal tract. IBS is characterized by chronic abdominal pain, intestinal motility disorders and stool changes, which significantly reduces the quality of life of patients. The article analyzes in detail the pathogenetic mechanisms of IBS, including the role of the gut–brain axis, gut microbiota and neuroendocrine factors. Special attention is paid to the pharmacotherapy of IBS in children, including the use of antidepressants, probiotics and herbal components, as well as the role of correctors of the motor activity of the digestive tract in relieving symptoms. Modern recommendations on the use of various classes of antidepressants are considered, taking into account their pharmacokinetic and pharmacodynamic characteristics. The prospects of using probiotics and herbal preparations in the complex therapy of IBS are also analyzed. The data obtained confirm the need for a personalized approach to the treatment of IBS, taking into account the genetic and physiological characteristics of patients.

Gut Neuropathies and Intestinal Motility Disorders.

The enteric nervous system plays a key role in the coordination of gastrointestinal motility together with sympathetic, parasympathetic, and extrinsic sensory pathways. In some cases, abnormalities in neural activity in these pathways contribute to disorders of gut motility. Where this is associated with damage or death of enteric neurons, usually detected by microscopy, this is considered a gut neuropathy. This review summarizes recent advances in the identification of neuropathies in a range of gastrointestinal motility disorders.

Functional constipation is associated with long-term clinical failure after gastric per-oral endoscopic myotomy for the treatment of gastroparesis.

This study investigates the role of functional constipation (FC) in predicting the long-term success of Gastric Per-oral Endoscopic Myotomy (G-POEM) for treating gastroparesis. This was a retrospective observational study. Patients who underwent G-POEM between July 2015 and August 2022 with > 6-month follow-up were included. The primary objective was to evaluate the relationship between FC and G-POEM success. Secondary objectives included documenting the role of other digestive motility disorders, history of eating disorders, chronic opioid use, and cannabis use. Multivariate logistic regression analysis was used to evaluate the relationship between clinical success and various parameters, including FC. 80 patients were included, 58 women (72.5%) and 22 men (27.5%) with a mean age of 51.78 years. The mean follow-up was 3.4 years. Clinical success was observed in 52.5% of the patients' post-G-POEM. 42.5% had FC, 17.7% had esophageal motility disorders (EMD), and 13.9% had other motility disorders. In univariate analysis, FC and EMD were more frequent in patients with failure: 57.89 vs 28.57%, p = 0.015 and 28.95 vs 7.32%, p = 0.017, respectively. In multivariate analysis, the presence of FC (OR = 0.281 [0.105; 0.75], p = 0.0113) was the only predictive factor for success. FC emerged as a significant predictor of lower clinical success rates after G-POEM. It suggests that an expanded gastrointestinal evaluation and treatment of other motility disorders may improve the outcomes for patients with gastroparesis treated with G-POEM.

Effects of Bifidobacterium lactis BLa80 on fecal and mucosal flora and stem cell factor/c-kit signaling pathway in simulated microgravity rats.

Simulated microgravity environment can lead to gastrointestinal motility disturbance. The pathogenesis of gastrointestinal motility disorders is closely related to the stem cell factor (SCF)/c-kit signaling pathway associated with intestinal flora and Cajal stromal cells. Moreover, intestinal flora can also affect the regulation of SCF/c-kit signaling pathway, thus affecting the expression of Cajal stromal cells. Cajal cells are the pacemakers of gastrointestinal motility. To investigate the effects of Bifidobacterium lactis (B. lactis) BLa80 on the intestinal flora of rats in simulated microgravity and on the gastrointestinal motility-related SCF/c-kit pathway. The internationally recognized tail suspension animal model was used to simulate the microgravity environment, and 30 rats were randomly divided into control group, tail suspension group and drug administration tail suspension group with 10 rats in each group for a total of 28 days. The tail group was given B. lactis BLa80 by intragastric administration, and the other two groups were given water intragastric administration, the concentration of intragastric administration was 0.1 g/mL, and each rat was 1 mL/day. Hematoxylin & eosin staining was used to observe the histopathological changes in each segment of the intestine of each group, and the expression levels of SCF, c-kit, extracellular signal-regulated kinase (ERK) and p-ERK in the gastric antrum of each group were detected by Western blotting and PCR. The fecal flora and mucosal flora of rats in each group were detected by 16S rRNA. Simulated microgravity resulted in severe exfoliation of villi of duodenum, jejunum and ileum in rats, marked damage, increased space between villi, loose arrangement, shortened columnar epithelium of colon, less folds, narrower mucosal thickness, reduced goblet cell number and crypts, and significant improvement after probiotic intervention. Simulated microgravity reduced the expressions of SCF and c-kit, and increased the expressions of ERK and P-ERK in the gastric antrum of rats. However, after probiotic intervention, the expressions of SCF and c-kit were increased, while the expressions of ERK and P-ERK were decreased, with statistical significance (P < 0.05). In addition, simulated microgravity can reduce the operational taxonomic unit (OTU) of the overall intestinal flora of rats, B. lactis BLa80 can increase the OTU of rats, simulated microgravity can reduce the overall richness and diversity of stool flora of rats, increase the abundance of firmicutes in stool flora of rats, and reduce the abundance of Bacteroides in stool flora of rats, most of which are mainly beneficial bacteria. Simulated microgravity can increase the overall richness and diversity of mucosal flora, increase the abundance of Bacteroides and Desulphurides in the rat mucosal flora, and decrease the abundance of firmicutes, most of which are proteobacteria. After probiotics intervention, the overall Bacteroidetes trend in simulated microgravity rats was increased. B. lactis BLa80 can ameliorate intestinal mucosal injury, regulate intestinal flora, inhibit ERK expression, and activate the SCF/c-kit signaling pathway, which may have a facilitating effect on gastrointestinal motility in simulated microgravity rats.

Neurogastroenterology and motility disorders in patients with cirrhosis.

Neurogastroenterology and motility disorders are complex gastrointestinal conditions that are prevalent worldwide, particularly affecting women and younger individuals. These conditions significantly impact the quality of life of people suffering from them. There is increasing evidence linking these disorders to cirrhosis, with a higher prevalence compared to the general population. However, the link between neurogastroenterology and motility disorders and cirrhosis remains unclear due to undefined mechanisms. In addition, managing these conditions in cirrhosis is often limited by the adverse effects of drugs commonly used for these disorders, presenting a significant clinical challenge in the routine management of patients with cirrhosis. This review delves into this connection, exploring potential pathophysiological links and clinical interventions between neurogastroenterology disorders and cirrhosis.

A multicenter study on enteral autonomy outcome of pediatric intestinal failure patients from a middle-income country.

To identify predictors of enteral autonomy and survival in pediatric intestinal failure patients followed up at three pediatric intestinal rehabilitation centers from a middle-income country. This retrospective multicenter cohort study evaluated patients with intestinal failure from three high-volume intestinal rehabilitation centers on long-term parenteral nutrition between 2014 and 2023. The primary outcome was status at the end of the follow-up: parenteral nutrition dependence, enteral autonomy, transplantation, or death. Secondary outcomes were complications resulting from treatment and current parenteral nutrition dependency index. Competing risk analysis, Cox regression, and a decision tree model were employed. The cohort comprised 207 patients with a median (interquartile range) age at admission of 6.2 (3.1; 12.9) months and a median follow-up of 29.4 (10.2; 49.6) months. Short bowel (85%) and motility disorders (10.6%) were the primary causes of intestinal failure. Cumulative incidence of 5-year for enteral autonomy and survival rates were 37% and 88%, respectively. Intestinal failure-associated liver disease was present in 24% of patients on admission. Enteral autonomy was associated with remnant intestine length >40cm (hazard ratio: 2.0; 95% confidence interval: 1.7; 3.6); age at admission <6.2 months (hazard ratio: 1.8; 95% confidence interval: 1.0; 3.3); and preserved ileocecal valve (hazard ratio: 3.4; 95% confidence interval: 1.9; 6.0). The overall mortality rate was 7.7%. The overall survival rate was 92.3% and the 5-year cumulative incidence of enteral autonomy was 37%. The probability of achieving enteral autonomy was associated with early arrival at the intestinal rehabilitation center and favorable bowel anatomy.

Bifidobacterium bifidum CCFM1359 alleviates intestinal motility disorders through the BDNF-TrkB pathway.

Intestinal motility disorder is characterised by abnormal intestinal motility function, often resulting in symptoms such as diarrhoea and constipation. Probiotics are increasingly recognised as an effective treatment for gastrointestinal disorders, including intestinal motility disorders. In this study, we used senna extract to induce an animal model of intestinal dysfunction characterised by BDNF downregulation. By assessing relevant indicators of intestinal dyskinesia, we found that Bifidobacterium bifidum CCFM1359 effectively alleviated the dyskinesia. However, this alleviating effect was nullified when a TrkB receptor inhibitor was introduced, suggesting that Bifidobacterium bifidum CCFM1359 operates through the BDNF-TrkB pathway. Further analysis revealed that Bifidobacterium bifidum CCFM1359 likely exerts its beneficial effects by regulating intestinal microecology (increasing the relative abundance of Bifidobacterium bifidum and valeric acid content while decreasing Faecalibacterium and butyric acid content), reducing intestinal inflammation (upregulating the anti-inflammatory factor IL-10 and downregulating pro-inflammatory factors TNF-α and IL-1β), and remodelling intestinal nerves (upregulating S100β and the excitatory neurotransmitter ACh, while downregulating the inhibitory neurotransmitter nNOS). This study provides a theoretical basis for using probiotics to alleviate intestinal motility disorders.