Neurogastroenterology and Motility最新文献

{"title":"Defining Pharyngeal and Upper Esophageal Sphincter Disorders on High-Resolution Manometry-Impedance: The Leuven Consensus.","authors":"Taher I Omari, Julia C F Maclean, Charles Cock, Timothy M McCulloch, Nogah Nativ-Zeltzer, Ashli K O'Rourke, Michal M Szczesniak, Peter I Wu, Jacqueline Allen, Yoichiro Aoyagi, Howell Henrian G Bayona, Silvia Carrión, Michelle R Ciucci, Kate Davidson, Shumon I Dhar, Shaheen Hamdy, Rebecca Howell, Corrine Jones, Molly A Knigge, An Moonen, Gregory N Postma, Jo Puntil-Sheltman, Anais Rameau, Julie Regan, Mistyka Schar, Nathalie Rommel","doi":"10.1111/nmo.70042","DOIUrl":"https://doi.org/10.1111/nmo.70042","url":null,"abstract":"<p><strong>Introduction: </strong>The Leuven Consensus provides a classification scheme for the diagnosis of pharyngeal and upper esophageal sphincter (UES) motor disorders using metrics derived from pharyngeal high-resolution manometry-impedance (P-HRM-I).</p><p><strong>Methods: </strong>Twenty-six experts with broad multidisciplinary backgrounds contributed their knowledge and experience to this initiative via a formal deliberative Delphi process. Guidance on a swallow assessment protocol as well as diagnostic criteria for UES dysfunction and pharyngeal contractile dysfunction is provided.</p><p><strong>Results: </strong>For UES dysfunction, the stepwise evaluation of UES and intrabolus pressure metrics under increasing bolus volume and/or viscosity conditions is used to confirm failure of manometric relaxation and opening of the UES region. For pharyngeal contractile dysfunction, the evaluation of contractile metrics is used to define pharyngeal hypocontractility or hypercontractility.</p><p><strong>Conclusion: </strong>These recommendations complement routine instrumental investigations and provide a standardized process, criteria, and nomenclature for P-HRM-I assessment of patients reporting symptoms of oropharyngeal dysphagia.</p>","PeriodicalId":19123,"journal":{"name":"Neurogastroenterology and Motility","volume":" ","pages":"e70042"},"PeriodicalIF":3.5,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electroacupuncture Promotes the Proliferation and Differentiation of Enteric Neural Precursor Cells via the PTEN/PI3K/Akt/mTOR Signaling Pathway in Diabetic Mice.","authors":"Jinlu Guo, Xin Yang, Jingze Yang, Fan Du, Shi Liu","doi":"10.1111/nmo.70040","DOIUrl":"https://doi.org/10.1111/nmo.70040","url":null,"abstract":"<p><strong>Background: </strong>Enteric neuronal loss significantly contributes to gastrointestinal (GI) motility disorders. Electroacupuncture (EA) can promote the regeneration of lost enteric neurons in diabetic mice, but its mechanisms are not fully understood. Nestin⁺/Ngfr⁺ cells can function as enteric neural precursor cells (ENPCs) to proliferate and differentiate into enteric neurons in adult mice. However, EA's effects on ENPCs remain unknown. The study aimed to investigate whether EA reversed enteric neuronal loss via regulation of ENPCs and its molecular basis.</p><p><strong>Materials and methods: </strong>The study utilized conventional C57BL/6J mice and ENPC-tracing transgenic mice. Streptozotocin-induced type 1 diabetic mouse, PI3K inhibitor, and PTEN inhibitor models were used. GI motility was evaluated by defecation frequency, fecal water content, and whole gut transit test. The alterations of enteric neurons, ENPCs, and PTEN/PI3K/Akt/mTOR signaling were detected by Western blot and immunofluorescence.</p><p><strong>Results: </strong>EA increased defecation frequency and fecal water content, reduced whole gut transit time, and increased the number of enteric neurons. Notably, EA inhibited ENPC apoptosis and facilitated ENPC proliferation and differentiation with a preferential into ChAT enteric neurons. Additionally, PTEN was decreased and PI3K/Akt/mTOR signaling was activated with EA. However, LY294002 (PI3K inhibitor) inhibited EA's effects on ENPCs, while BpV(HOpic) (PTEN inhibitor) partially rescued these inhibitory effects.</p><p><strong>Conclusions: </strong>EA alleviates diabetic enteric neuropathy by regulating ENPC dynamics through the PTEN/PI3K/Akt/mTOR signaling pathway. Notably, EA-mediated anti-apoptotic and pro-proliferative effects on ENPCs, and their preferential cholinergic differentiation establish EA as a multimodal therapy that bridges neuromodulation with precursor cell biology, offering an alternative strategy for GI motility disorders.</p>","PeriodicalId":19123,"journal":{"name":"Neurogastroenterology and Motility","volume":" ","pages":"e70040"},"PeriodicalIF":3.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intrarectal Injections of Botulinum Toxin for the Treatment of Urge Fecal Incontinence: Long-Term Results of an FI-Toxin Cohort Study.","authors":"Charlotte Desprez, Charlène Brochard, Véronique Vitton, Isabelle Etienney, Frank Zerbib, Gérard Amarenco, Francois Mion, Michel Queralto, Guillaume Gourcerol, Laurent Siproudhis, Henri Damon, Julie Philip, Elie Lacroix, André Gillibert, Anne-Marie Leroi","doi":"10.1111/nmo.70025","DOIUrl":"https://doi.org/10.1111/nmo.70025","url":null,"abstract":"<p><strong>Background: </strong>The efficacy and safety of intrarectal botulinum toxin A (BoNT/A) injections in patients with urge fecal incontinence (FI) were evidenced in a large, multicenter, randomized, placebo-controlled study (FI-TOXIN). The aims of the present study were to evaluate the long-term efficacy and safety of intrarectal BoNT/A injections in a real-world setting in patients who participated in the FI-TOXIN study.</p><p><strong>Methods: </strong>Data collected from patients who had previously participated in the FI-TOXIN study in 8 French centers from November 2015 to November 2020 were retrospectively analyzed. Given the transient effect of BoNT/A, patients who had received the first injection in the FI-TOXIN study could be re-injected if symptoms recurred. Information on re-injections, satisfaction of patients, severity of FI symptoms, adverse effects, and the switch to another treatment was retrospectively collected from medical charts between M6 (end of the double-blind phase) and M54 of the inclusion in the FI-TOXIN study.</p><p><strong>Key results: </strong>Of the 191 patients in the initial FI-TOXIN cohort, 147 (77.0%) were included at M6. Between M6 and M54, 114 of these patients received 233 injections (68 first injections, 165 re-injections). Satisfaction information was available for 70 patients, of whom 43/70 (61.4%) were satisfied with all their injections. The treatment failed in 52/147 (35.4%) of the patients, with rejections of the treatment by patients due to insufficient perceived efficacy (34 patients), adverse effects or poor tolerance (11 patients), or switch to a surgical treatment (23 patients). Nonsevere adverse events were recorded after 45/233 (19.3%) injections. The two severe adverse events (cervical cancer and psychiatric hospitalization) were unrelated to the treatment.</p><p><strong>Conclusions: </strong>Intrarectal injections of BoNT/A displayed moderate long-term efficacy without major adverse effects.</p>","PeriodicalId":19123,"journal":{"name":"Neurogastroenterology and Motility","volume":" ","pages":"e70025"},"PeriodicalIF":3.5,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Rapid F0 CRISPR Screen in Zebrafish to Identify Regulator Genes of Neuronal Development in the Enteric Nervous System.","authors":"Ann E Davidson, Nora R W Straquadine, Sara A Cook, Christina G Liu, Chuhao Nie, Matthew C Spaulding, Julia Ganz","doi":"10.1111/nmo.70009","DOIUrl":"https://doi.org/10.1111/nmo.70009","url":null,"abstract":"<p><strong>Background: </strong>The neural crest-derived enteric nervous system (ENS) provides the intrinsic innervation of the gut with diverse neuronal subtypes and glial cells. The ENS regulates all essential gut functions, such as motility, nutrient uptake, immune response, and microbiota colonization. Deficits in ENS neuron numbers and composition cause debilitating gut dysfunction. Yet, few studies have identified genes that control neuronal differentiation and the generation of the diverse neuronal subtypes in the ENS.</p><p><strong>Methods: </strong>Utilizing existing CRISPR/Cas9 genome editing technology in zebrafish, we have developed a rapid and scalable screening approach for identifying genes that regulate ENS neurogenesis.</p><p><strong>Key results: </strong>As a proof-of-concept, F0 guide RNA-injected larvae (F0 crispants) targeting the known ENS regulator genes sox10, ret, or phox2bb phenocopied known ENS phenotypes with high efficiency. We evaluated 10 transcription factor candidate genes as regulators of ENS neurogenesis and function. F0 crispants for five of the tested genes have fewer ENS neurons. Secondary assays in F0 crispants for a subset of the genes that had fewer neurons reveal no effect on enteric progenitor cell migration but differential changes in gut motility.</p><p><strong>Conclusions: </strong>Our multistep, yet straightforward CRISPR screening approach in zebrafish tests the genetic basis of ENS developmental and disease gene functions that will facilitate the high-throughput evaluation of candidate genes from transcriptomic, genome-wide association, or other ENS-omics studies. Such in vivo ENS F0 crispant screens will contribute to a better understanding of ENS neuronal development regulation in vertebrates and what goes awry in ENS disorders.</p>","PeriodicalId":19123,"journal":{"name":"Neurogastroenterology and Motility","volume":" ","pages":"e70009"},"PeriodicalIF":3.5,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Finding the Line Between Avoidant/Restrictive Food Intake Disorder and Refractory Disorders of Gut-Brain Interaction Using Lenient vs. Strict Severity Criteria: A Retrospective Exploratory Analysis From a Single Tertiary Neurogastroenterology Centre.","authors":"Lee David Martin, Asma Fikree, Natalia Zarate-Lopez, Karin Martinkova, Concetta Brugaletta, Chris Perrin, Ursula Philpot","doi":"10.1111/nmo.70043","DOIUrl":"https://doi.org/10.1111/nmo.70043","url":null,"abstract":"<p><strong>Background: </strong>Avoidant/restrictive food intake disorder (ARFID) is common among adults with disorders of gut-brain interaction (DGBI) presenting to gastroenterology settings. Symptoms overlap between ARFID and DGBI. How the severity of ARFID is defined can impact rates of diagnosis. Importantly, a diagnosis of ARFID can only be applied when the eating disturbance exceeds that expected from the DGBI condition. This leads to diagnostic challenges for the gastroenterology team. We aimed to explore how we could better identify \"ARFID presentation\" by reaching a clinically meaningful cut-off and distinct categories for separating DGBI from ARFID and where DGBI and ARFID overlap.</p><p><strong>Methods: </strong>A retrospective review of electronic health records (EHR) was conducted on 33 patients 88% female (29/33), with a median age of 44.3 ± 15.5 (range 18-73 years). All had a Rome IV diagnosed DGBI and were refractory to standard medical care, requiring both gastro-psychology and dietitian input in a tertiary care Neurogastroenterology service during 2019. Severity criteria for meeting either strict or lenient ARFID criteria A were defined based on DSM-5 and best practice recommendations.</p><p><strong>Results: </strong>The majority (82%) met a form of ARFID criteria A. However, by applying severity levels, 33% met criteria for strict ARFID, while 49% met lenient criteria, and 18% did not meet any criteria.</p><p><strong>Discussion: </strong>Adults with refractory DGBI who require both dietetic and psychological support can meet both lenient and strict ARFID severity criteria. Future research should explore if utilizing severity markers can help separate the heterogeneity of DGBI + ARFID and inform diagnostic and treatment approaches.</p>","PeriodicalId":19123,"journal":{"name":"Neurogastroenterology and Motility","volume":" ","pages":"e70043"},"PeriodicalIF":3.5,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial Intelligence Model for Time Series Classification: Prediction of Delayed Balloon Expulsion Test Using High-Resolution Anorectal Manometry Data and Time-Series Integrated Pressurized Volume.","authors":"Myeongsook Seo, Kiwon Yoon, Kee Wook Jung, Seung-Jae Myung, Satish S C Rao, Segyeong Joo","doi":"10.1111/nmo.70044","DOIUrl":"https://doi.org/10.1111/nmo.70044","url":null,"abstract":"<p><strong>Background: </strong>We previously demonstrated the novel concept of using the integrated pressurized volume (IPV) with high-resolution anorectal manometry (HRAM) and found that it was predictive of delayed balloon expulsion (BE) test results. However, previous IPV methods did not account for chronological changes in anorectal force. To fully utilize the temporal dynamics of HRAM data and enhance BE test prediction, we introduced time-series IPVs (TS-IPVs) and developed an artificial intelligence (AI)-based diagnostic model.</p><p><strong>Methods: </strong>A total of 300 patients with constipation (130 male and 170 female patients) were enrolled and underwent HRAM and BE tests from September 2020 to May 2021. The TS-IPVs were calculated within a particular time interval during the push maneuver. Convolutional neural networks (CNNs) and a long short-term memory (LSTM) network were applied to predict BE test results.</p><p><strong>Key results: </strong>Delayed BE was observed in 69 (53.1%) male and 49 (28.8%) female patients. According to the receiver operating characteristic curve analysis, the TS-IPV ratio between the upper 1 cm and lower 3 cm of the anal canal (TS-IPV₁₃ ratio) was the best parameter for predicting BE test results in all patients. Using the TS-IPV₁₃ ratio, the proposed model achieved area under the curve (AUC) values of 0.988 and 0.996 for female and male patients, respectively.</p><p><strong>Conclusions and inferences: </strong>Our AI model accurately classified delayed BE test results using raw HRAM data and TS-IPVs of male and female patients with an AUC of 0.99. Furthermore, the model used time-variant HRAM pressure data and TS-IPVs throughout the push maneuver without any data loss; therefore, TS-IPV could be used as a more reliable marker than conventional parameters for classifying delayed BE test results.</p>","PeriodicalId":19123,"journal":{"name":"Neurogastroenterology and Motility","volume":" ","pages":"e70044"},"PeriodicalIF":3.5,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diaphragmatic Flutter Disease: Key Findings in Esophageal Manometry and Biofeedback Treatment.","authors":"Ezquerra-Durán Alberto, Ayala Haro Noé, Isis K Araujo, Elizabeth Barba","doi":"10.1111/nmo.70041","DOIUrl":"https://doi.org/10.1111/nmo.70041","url":null,"abstract":"<p><strong>Background: </strong>Diaphragmatic flutter (DF) is a rare condition characterized by involuntary contractions of the diaphragmatic muscle, often accompanied by accessory respiratory muscle contractions. Symptoms can include epigastric pulsations, abdominal pain, and reflux. Diagnosis is challenging, and treatment is based on individual cases. This study presents the first case series of DF assessed using high-resolution esophageal manometry (HREM), electromyography (EMG), and plethysmography belts, and the symptomatic improvement through biofeedback therapy.</p><p><strong>Methods: </strong>This case series includes patients with refractory abdominal spasms referred to the digestive motility department from 2018 to 2024.</p><p><strong>Results: </strong>Two patients were diagnosed with DF using HREM, which reveals a characteristic pattern of oscillating increases in intragastric pressure, repetitive crural diaphragm spasms, and pharyngeal contraction during abdominal spasms. Symptomatic control was achieved following abdomino-thoracic biofeedback (ATB) therapy by plethysmography belts.</p><p><strong>Conclusions: </strong>High-resolution esophageal manometry offers a reliable, non-invasive method for diagnosis of DF, presenting a specific manometric pattern. ATB appears to be an effective treatment for DF, suggesting that voluntary but unconsciously initiated movement disorders may contribute to the condition.</p>","PeriodicalId":19123,"journal":{"name":"Neurogastroenterology and Motility","volume":" ","pages":"e70041"},"PeriodicalIF":3.5,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut-Directed Hypnotherapy for Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis.","authors":"Elizabeth C Adler, Emma H Levine, Allison N Ibarra, Eshandeep S Boparai, Yun-Yi Hung, Quincy D McCrary, Jeffrey K Lee","doi":"10.1111/nmo.70037","DOIUrl":"https://doi.org/10.1111/nmo.70037","url":null,"abstract":"<p><strong>Background: </strong>Gut-directed hypnotherapy has been shown to be an effective treatment for irritable bowel syndrome, but prior studies have been small with variable delivery modalities. This systematic review and meta-analysis investigates the efficacy of gut-directed hypnotherapy for irritable bowel syndrome (IBS) symptoms and the impact of delivery characteristics.</p><p><strong>Methods: </strong>PubMed, Embase, and Web of Science were searched. Titles and abstracts, then full text articles, were screened for inclusion criteria. Studies were extracted and assessed for bias using the Cochrane Collaboration risk-of-bias tool. A meta-analysis was performed to assess the impact of gut-directed hypnotherapy on global IBS symptoms and pain. A sub-group analysis was conducted to assess the impact of gut-directed hypnotherapy delivery characteristics on IBS-related outcomes.</p><p><strong>Results: </strong>Twelve studies in 11 papers met inclusion criteria, involving 1158 patients with IBS. Eight studies provided continuous measures sufficient for meta-analysis. On systematic review, all 12 studies found gut-directed hypnotherapy to be superior to the comparator; nine were statistically significant. On meta-analysis, gut-directed hypnotherapy improved global IBS symptoms (SMD 0.73 [-0.09-1.55], I² 93%). Gut-directed hypnotherapy with high-volume delivery and gut-directed hypnotherapy delivered in groups showed statistically significant improvement in global IBS symptoms (SMD 0.56 [0.29-0.83], I² 0%; SMD 0.41 [0.05-0.77], I² 61%). Gut-directed hypnotherapy also significantly improved pain more than its comparator groups (SMD 0.25 [0.01-0.49], I² 17%).</p><p><strong>Conclusion: </strong>Gut-directed hypnotherapy may improve global symptoms of IBS. In particular, GDH improved pain symptoms compared to other standard IBS interventions. GDH delivered in groups was effective at reducing global IBS symptoms compared to standard interventions.</p>","PeriodicalId":19123,"journal":{"name":"Neurogastroenterology and Motility","volume":" ","pages":"e70037"},"PeriodicalIF":3.5,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Burden of Fecal Incontinence: Evaluating the Societal Impact in Terms of Economic Burden and Health-Related Quality of Life.","authors":"Sadé L Assmann, Merel L Kimman, Stéphanie O Breukink, Daniel Keszthelyi","doi":"10.1111/nmo.70036","DOIUrl":"https://doi.org/10.1111/nmo.70036","url":null,"abstract":"<p><strong>Introduction: </strong>Fecal incontinence (FI) is a chronic condition characterized by the involuntary loss of stool, significantly impacting health-related quality of life (HRQoL) and imposing a substantial economic burden on society.</p><p><strong>Methods: </strong>This bottom-up, retrospective, cross-sectional burden of disease study offers a comprehensive cost analysis of FI in a Dutch population sample. Utilizing the iMTA Medical Consumption Questionnaire (MCQ) and the iMTA Productivity Cost Questionnaire (PCQ), we analyzed costs over a 3-month period from a societal perspective, which encompasses healthcare costs, out-of-pocket expenses, and productivity losses. Non-parametric bootstrapping was applied to identify differences in costs between several subgroups of patients. Additionally, we assessed HRQoL using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire. Differences in HRQoL between subgroups were determined using the nonparametric Mann-Whitney U test.</p><p><strong>Results: </strong>Cost and HRQoL data were collected from 80 FI patients aged 39-89 (82.5% female). The mean societal costs were €2424 per patient per quarter, of which €1572 can be contributed to healthcare costs. Notably, unemployed patients incurred significantly higher costs compared to employed and retired patients. No significant difference in costs was seen between subgroups based on gender, age, educational level, or frequency of FI episodes. The mean HRQoL score was 0.72 (SD 0.78). Younger and unemployed patients reported lower HRQoL scores.</p><p><strong>Conclusion: </strong>This study demonstrates that FI negatively impacts HRQoL and has a considerable impact on societal costs, extending beyond direct healthcare expenses. Policymakers, healthcare providers, and employers should take these findings into account when designing management strategies and allocating resources for FI treatment and support.</p>","PeriodicalId":19123,"journal":{"name":"Neurogastroenterology and Motility","volume":" ","pages":"e70036"},"PeriodicalIF":3.5,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Direct Stimulation of Gastric Smooth Muscle Cells via G_q Proteins With Light.","authors":"David Zipf, Markus Vogt, Udhayabhaskar Sathyanarayanan, Ahmed Wagdi, Johannes Riebeling, Robert Patejdl, Tobias Bruegmann","doi":"10.1111/nmo.70028","DOIUrl":"https://doi.org/10.1111/nmo.70028","url":null,"abstract":"<p><strong>Background: </strong>Optogenetics is a cutting-edge approach that can enable direct stimulation of gastric smooth muscle cells (SMC) by combining cell-specific overexpression of light-sensitive proteins with light stimulation. We previously demonstrated that direct optogenetic stimulation of gastric SMC via depolarization can restore contractility and food propulsion and could become a new treatment strategy for gastroparesis. The human receptor Neuropsin (hOPN5) enables activation of G_q signaling with UV light. Herein, we explore this new strategy for direct optogenetic stimulation of gastric SMC.</p><p><strong>Methods: </strong>We used a transgenic mouse model expressing hOPN5 in fusion with eYFP. Antral longitudinal smooth muscle strips were used for isometric force measurements and whole stomachs for intragastric pressure measurements, comparing light stimulation to other stimuli. Adeno-associated virus (AAV) serotypes were screened for efficiency in transducing cultured gastric SMC, and transduced cells were tested by Ca²⁺ imaging.</p><p><strong>Results: </strong>hOPN5 expression was restricted to and found in ~1/3 of SMC in the stomach. UV light induced isometric force and increased intragastric pressure only in transgenic mice similarly to electrical field stimulation and reached approximately 1/3 of the force induced by global depolarization and muscarinic receptor activation. Importantly, optical stimulation remained effective in an ex vivo gastroparesis model. AAV 2.5 was by far the most effective serotype for SMC transduction, and UV light triggered Ca²⁺ transients in SMC expressing hOPN5.</p><p><strong>Conclusion: </strong>hOPN5 is a new and effective tool to directly stimulate gastric SMC to control contractility with light. Thus, it is an additional and complementary approach to light-induced membrane depolarization to restore gastric motility.</p>","PeriodicalId":19123,"journal":{"name":"Neurogastroenterology and Motility","volume":" ","pages":"e70028"},"PeriodicalIF":3.5,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}