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Objective: Cognitive Behavioral Therapy (CBT) for youth with Disorders of Gut‐Brain Interaction (DGBIs) is effective; however, there are calls in the field to strengthen the evidence base and identify specific mechanisms of treatment that yield the most benefit for this patient population. A unique, systematic treatment approach of CBT with initial evidence for success for pediatric patients with DGBIs was evaluated to further demonstrate its clinical utility in this population. Methods: This was a retrospective study of 42 pediatric patients aged 11–17 years with DGBIs, who were diagnosed and referred for CBT by pediatric gastroenterology providers. Providers also completed a survey rating acceptability and effectiveness of CBT. The systematic CBT approach included 10 sessions delivered by a psychologist at an integrated Pediatric GI Clinic. Results: Review of 42 pediatric charts showed significant decreases in self‐reported functional disability, abdominal pain, as well as depression and anxiety symptoms pre‐ to post‐CBT completion. A moderation effect was observed where patients reporting higher levels of depressive symptoms and primary symptom of abdominal pain reported smaller reductions in functional impairment compared to those with lower levels of depression and primary symptom of nausea or vomiting. Pediatric Gastroenterology providers were satisfied with this psychological treatment approach. Conclusions: This study provides evidence for acceptability and effectiveness of implementation of a systematic CBT approach for pediatric DGBIs in an integrated GI clinic, as well as areas worthy of future research, including identifying the most important mechanisms of treatment and factors that influence treatment response. [ABSTRACT FROM AUTHOR]

Transition services—programs that support adolescents and young adults (AYAs) as they move from a child‐centered to a more autonomous, adult‐orientated healthcare system—have been associated with improved short‐ and long‐term healthcare outcomes. Unfortunately, there is a paucity of evidence exploring transition services within the neurogastroenterology and motility (NGM) field. The overall aim of this article, endorsed by the American Neurogastroenterology and Motility Society and European Society of Neurogastroenterology and Motility, is to promote a discussion about the role of transition services for patients with NGM disorders. The AYAs addressed herein are those who have: (a) a ROME positive disorder of gut–brain interaction (DGBI), (b) a primary or secondary motility disorder (including those with motility disorders that have been surgically managed), or (c) an artificial feeding requirement (parenteral or enteral tube feeding) to manage malnutrition secondary to categories (a) or (b). The issues explored in this position paper include the specific physical and psychological healthcare needs of patients with NGM disorders; key healthcare professionals who should form part of a secondary care NGM transition service; the triadic relationship between healthcare professionals, caregivers, and patients; approaches to selecting patients who may benefit most from transition care; methods to assess transition readiness; and strategies with which to facilitate transfer of care between healthcare professionals. Key areas for future research are also addressed, including the construction of NGM‐specific transition readiness questionnaires, tools to assess post‐transfer healthcare outcomes, and educational programs to train healthcare professionals about transition care in NGM. [ABSTRACT FROM AUTHOR]

This paper introduces a metric capable of tracking a hypothetical brainstem “switching” mechanism involved in regulating the afferent influence of blood pressure on the vagal efferent control of heart rate. In theory, this metric could be applied to evaluate the “efficiency” of brainstem pathways involved in common mechanisms of autonomic function involving the vagal influences on the gut as well as the heart. Thus, by exploring the dynamic “efficiency” of the brainstem feedback circuit linking heart rate to posture, a clinically relevant index of vagal flexibility might be extracted that would provide a generalizable window into the vagal regulation of both the heart and gut. Recent research supports this contention and has documented that this metric, VE, appears to covary with disorders of the gut. Clinical application of this metric might identify individual vulnerabilities that frequently reflect symptoms assumed to have features of a dysregulated autonomic nervous system (i.e., dysautonomia). If this is confirmed by additional research, then this objective measure of neural regulation of autonomic function might provide insight into the pathogenesis of disorders of gut–brain interaction. [ABSTRACT FROM AUTHOR]

This article explores the role of enteric glia in the function of the intestinal epithelial barrier. The gut lining acts as a barrier, allowing nutrients to pass through while keeping out pathogens. Increased permeability of the intestinal barrier, known as "leaky gut," has been linked to various gastrointestinal and extraintestinal disorders. Enteric glia, which are present in all layers of the gut, play a crucial role in regulating the gut epithelial barrier function. They can regulate ion and fluid transport in the intestine and may contribute to the treatment of functional diarrheal diseases. However, their specific biological functions are not fully understood, and further research is needed to understand their mechanisms and interactions. Enteric glia have also been implicated in various disorders, including Parkinson's disease and psychiatric disorders. The document provides a list of references that explore the structure, function, and interactions of enteric glial cells, as well as their involvement in different conditions and processes in the gastrointestinal tract. [Extracted from the article]

المخلص: أهداف البحث:تعترف الدراسة بأن إدارة موه الرأس نسبيا بسيطة، إلا أنه لا تزال هناك بعض المضاعفات التي يمكن أن تؤثر على التشخيص. واحدة من المضاعفات الأكثر إثارة للخوف هي هجرة التحويلة. على الرغم من ندرتها، إلا أن هجرة الأمعاء هي أكثر أنواع الهجرة شيوعا. تم جمع تقارير كافية للدراسة. الهدف هو فهم هذه المضاعفة بشكل أفضل للحد من حدوثها.طرق البحث:شملت الدراسة مراجعة حالات هجرة التحويلة الشرجية من قواعد بيانات ''ببميد'' و ''سكوبوس''. ما مجموعه ٤٩ سجل تم تضمينها تصف ٥٦ حالة سريرية. تم تضمين حالة سريرية إضافية تم إدارتها بواسطة فريق الدراسة، مما يجعل المجموع ٥٧ حالة. جمعت وحللت الدراسة البيانات الديموغرافية والسريرية، ونهج الإدارة، والنتائج، وغيرها من المعايير ذات الصلة. تم تضمين حالات اختراق الأمعاء، وهي عامل أولي للإخراج الشرجي. التزمت الدراسة ببيان العناصر المفضلة للتقارير في الاستعراضات المنهجية والتحليلات التلوية من عام ٢٠٠٩.النتائج:تم ملاحظة الإخراج الشرجي في ٨٢٪ من الحالات، وكان 68% منهم من الأطفال الذكور. كانت الفئة العمرية من شهر واحد إلى ٧٥ سنة، مع فقط ١٨٪ تشمل المرضى فوق سن ١٤ عاما. كانت موه الرأس الخلقي هو السبب في ٦٦٪ من الحالات. تفاوت الفاصل الزمني بين إدخال التحويلة والهجرة بشكل كبير من 12 يوم إلى 19 عام. وفي 55% من الحالات، حدثت الهجرة خلال الـ 12 شهرا الأولى، بينما حدثت 7 حالات في السنة الثانية، و8 حالات في السنة الثالثة، و3 حالات في السنة الرابعة، و6 حالات بعد 4 سنوات. في 70% من المرضى، تم سحب الأنبوب من خلال فتحة الشرج، بينما تم استخدام فتح البطن أو منظار البطن في 14% من الحالات. تم ملاحظة مضاعفات معدية، بما في ذلك التهاب السحايا، في ٣٥٪ من المرضى. تم الإبلاغ عن ست حالات فقط من التهابات الجهاز الخارجي العصبي، بما في ذلك حالتين من التهاب الصفاق وأربع حالات من الخراج تحت الجلد والمجموعات المصابة. كانت النتيجة الإجمالية إيجابية في الغالب، على الرغم من وفاة مريضين بسبب مضاعفات الهجرة.الاستنتاجات: هجرة التحويلة الشرجية والأمعاء، على الرغم من ندرتها، هي مضاعفة مهمة تكون ملاحظتها بشكل رئيسي في الأطفال الذكور. يحدث هذا في الغالب خلال الأسابيع أو الأشهر الأولى بعد الجراحة الأولية. غالبا ما تؤدي هذه الهجرة إلى مضاعفات معدية داخل الجهاز العصبي المركزي، والتي يمكن أن تهدد الحياة. المطلوب إدارة عاجلة، وفي معظم الحالات، تكون إزالة التحويلة من خلال فتحة الشرج كافية، ما لم تكن هناك مؤشرات واضحة لإجراء جراحة في البطن، مثل التهاب الصفاق. يؤدي التدخل المبكر في العادة إلى نتائج إيجابية، مما يبرز أهمية العلاج بالمنظار لموه الرأس. Abstract: Background: One of the most feared complications of hydrocephalus is shunt migration. Although rare, bowel migration is the most commonly encountered type of migration. The relatively high frequency of this occurrence allowed us to gather a substantial number of reports for study. Objectives: The aim of this study was to better understand this complication and aid in decreasing its incidence. Methods: The PubMed and Scopus databases were searched for cases of anal shunt migration. In total, 49 records describing 56 clinical cases were included in this review. Additionally, we present and include the clinical case of a patient managed by our team; therefore, 57 cases were included in this study. Relevant parameters were collected, organized, analyzed, and discussed. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement from 2009. Results: Extrusion through the anus was observed in 82% of cases, 68% of which were in males. The age range varied from 1 month to 75 years. Congenital hydrocephalus was the etiology in 66% of cases. The time interval between shunt insertion and migration varied from 12 days to 19 years. In 70% of patients, the tube was pulled out through the anus, whereas a laparotomy or laparoscopy was used in 14% of cases. Infectious complications were noted in 35% of patients. The overall outcome was mostly favorable; two patients died as a complication of the migration. Conclusions: Bowel and anal shunt migration is a relatively rare complication occurring predominantly within the initial weeks after the initial surgery. This condition leads to infectious complications, which can potentially be life-threatening. Urgent management is required, and in most cases, the removal of the shunt through the anus is sufficient. Early intervention generally results in favorable outcomes.

Disorders of brain–gut interaction (DGBI) are highly prevalent in our community with a negative burden on the quality of life and function. Symptoms are frequently food‐induced, and psychological disorders are commonly co‐morbid and contribute greatly to symptom severity and healthcare utilization, which can complicate management. Pathophysiological contributors to the development and maintenance of DGBI are best appreciated within the biopsychosocial model of illness. Established treatments include medical therapies targeting gastrointestinal physiology, luminal microbiota or visceral sensitivity, dietary treatments including dietary optimization and specific therapeutic diets such as a low‐FODMAP diet, and psychological interventions. The traditional "medical model" of care, driven predominantly by doctors, poorly serves sufferers of DBGI, with research indicating that a multidisciplinary, integrated‐care approach produces better outcomes. This narrative review explores the current evidence for multidisciplinary care and provides the best practice recommendations for physicians and healthcare systems managing such patients. [ABSTRACT FROM AUTHOR]

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Defecation function is negatively impacted in patients with neurogenic bowel dysfunction (NBD), who require effective bowel care for stool evacuation. NBD comprises fecal incontinence and/or constipation, which can reduce the quality of life and dignity. Transanal irrigation (TAI) is recommended by several clinical guidelines as the second-line treatment after conservative treatment and before surgical options are considered. As the only class in the second-line treatment with an established safety and efficacy profile, the mechanism of action of TAI has not fully been elucidated when administered through a rectal catheter with a balloon. This review examines the current understanding regarding the mechanism of action of TAI, with a focus on the pathophysiology of neurogenic bowel and irregular defecation. By understanding the functional implications of TAI, clinicians may be better able to integrate this modality into bowel care programs, especially for patients with NBD who have significant constipation due to delayed colonic motility and impaired stool emptying with loss of voluntary control of defecation, and those who are unresponsive to conservative treatment, including enemas. [ABSTRACT FROM AUTHOR]

Abstract Disorders of brain–gut interaction (DGBI) are highly prevalent in our community with a negative burden on the quality of life and function. Symptoms are frequently food‐induced, and psychological disorders are commonly co‐morbid and contribute greatly to symptom severity and healthcare utilization, which can complicate management. Pathophysiological contributors to the development and maintenance of DGBI are best appreciated within the biopsychosocial model of illness. Established treatments include medical therapies targeting gastrointestinal physiology, luminal microbiota or visceral sensitivity, dietary treatments including dietary optimization and specific therapeutic diets such as a low‐FODMAP diet, and psychological interventions. The traditional “medical model” of care, driven predominantly by doctors, poorly serves sufferers of DBGI, with research indicating that a multidisciplinary, integrated‐care approach produces better outcomes. This narrative review explores the current evidence for multidisciplinary care and provides the best practice recommendations for physicians and healthcare systems managing such patients.

Background: Neurogastroenterological disorders (NGDs) are highly prevalent and substantially impact patients' quality of life. Effective treatment of NGDs depends on the competence and training of medical caregivers. Students' perceived competence in neurogastroenterology and its place in medical school curricula are assessed in this study. Methods: A multi‐center digital survey among medical students was conducted at five universities. Self‐ratings of competence regarding basic mechanisms, diagnosis, and treatment of six chronic medical conditions were assessed. These included irritable bowel syndrome (IBS), gastroesophageal reflux disease, and achalasia. Ulcerative colitis, hypertension, and migraine were included as references. Key Results: Of 231 participants, 38% remembered that neurogastroenterology was covered in their curriculum. Highest competence ratings were stated for hypertension and the lowest for IBS. These findings were identical for all institutions irrespective of their curricular model and demographic parameters. Students who remembered neurogastroenterology as a part of their curriculum reported higher competence ratings. According to 72% of students, NGDs should be highlighted more prominently in the curriculum. Conclusions & Inferences: Despite its epidemiological relevance, neurogastroenterology is only weakly represented in medical curricula. Students report low levels of subjective competence in handling NGDs. In general, assessing the learners' perspective on an empirical basis may enrichen the process of national standardization of medical school curricula. [ABSTRACT FROM AUTHOR]

Background: Non‐allergenic, low molecular weight components of pollen grains are suspected to trigger changes in gut functions, sometimes leading to inflammatory conditions. Based on extensive neuroimmune communication in the gut wall, we investigated the effects of aqueous pollen extracts (APE) on enteric and spinal sensory neurons. Methods: Using Ca2+ and fast potentiometric imaging, we recorded the responses of guinea‐pig and human submucous and guinea‐pig dorsal root ganglion (DRG) neurons to microejection of low (<3 kDa) and high (≥3 kDa) molecular weight APEs of birch, ragweed, and hazel. Histamine was determined pharmacologically and by mass spectrometry (LC–MS/MS). Key Results: Birch APE<3kDa evoked strong [Ca+2]i signals in the vast majority of guinea‐pig DRG neurons, and in guinea‐pig and human enteric neurons. The effect of birch APE≥3kDa was much weaker. Fast neuroimaging in human enteric neurons revealed an instantaneous spike discharge after microejection of birch, ragweed, and hazel APE<3kDa [median (interquartile range) at 7.0 Hz (6.2/9.8), 5.7 Hz (4.4/7.1), and 8.4 Hz (4.3/12.5), respectively]. The percentage of responding neurons per ganglion were similar [birch 40.0% (33.3/100.0), ragweed 50.8% (34.4/85.6), and hazel 83.3% (57.1/100.0)]. A mixture of histamine receptor (H1–H3) blockers significantly reduced nerve activation evoked by birch and ragweed APEs<3kDa, but was ineffective on hazel. Histamine concentrations in ragweed, birch and hazel APE's < 3 kDa were 0.764, 0.047, and 0.013 μM, respectively. Conclusions: Allergen‐free APEs from birch, ragweed, and hazel evoked strong nerve activation. Altered nerve‐immune signaling as a result of severe pollen exposure could be a pathophysiological feature of allergic and non‐allergic gut inflammation. [ABSTRACT FROM AUTHOR]

Neurogastroenterology and motility is a new but advanced subspecialty within gasteroenterology that cater to difficult, persistent and refractory gut-brain symptoms. Hospital USM has the country's first and new state-of-the art motility lab that was recently launched on the 25 May 2023, and is covered in nationwide media. Another first is the Brain-Gut Clinic, established on the 16 November 2022. The clinic is a new concept that builds on unique multiple disciplines in relation to the gut-brain axis. It is hoped that there will be more awareness on the existence of neurogastroenterology and motility among doctors and community, and that more research can be forthcoming to reduce the disease burden. [ABSTRACT FROM AUTHOR]

Background: Disorders of the gut-brain axis are public diseases ("Volkskrankheiten") and are among the most frequent reasons to visit a doctor. Despite their great medical and socio-economic importance, patients suffering from these disorders are often not taken seriously and, therefore, do not receive sufficient diagnostic evaluation, or a diagnosis, in conformity with the relevant guidelines. In addition, the inadequate compensation of services makes handling of neurogastroenterological disorders increasingly unattractive. As a result, neurogastroenterology is under-represented in medical curricula, with a decreasing number of scientists in academia who are familiar with this field in Germany., Summary: The prevalence of neurogastroenterological diseases, which is associated with the need for medical care, should create corresponding care as a "bottom-up" development. However, this is not possible in the German healthcare system, due to the inadequate reimbursement structures. Therefore, a "top-down" strategy must be developed through health policy directives, directing the establishment of neurogastroenterology units based on quality parameters and need. These centers must form comprehensive network structures and share essential information on neurogastroenterological diseases with general practitioners, clinicians, and patients. Appropriate apps that also focus on interdisciplinary care with the involvement of various specialist disciplines (e.g., gastroenterology, neurology, gynecology, urology, psychology, psychosomatics, nutritional medicine) would be helpful for this purpose., Key Messages: Neurogastroenterology units are important and should be interdisciplinary and located in tertiary centers. Due to the lack of incentives in the German healthcare system, they must be instituted through health policy directives from the top down., Competing Interests: The author has no conflicts of interest to declare., (© 2024 S. Karger AG, Basel.)

Dietary, microbial, and inflammatory factors modulate the gut-brain axis and influence physiological processes ranging from metabolism to cognition. The gut epithelium is a principal site for detecting such agents, but precisely how it communicates with neural elements is poorly understood. Serotonergic enterochromaffin (EC) cells are proposed to fulfill this role by acting as chemosensors, but understanding how these rare and unique cell types transduce chemosensory information to the nervous system has been hampered by their paucity and inaccessibility to single-cell measurements. Here, we circumvent this limitation by exploiting cultured intestinal organoids together with single-cell measurements to elucidate intrinsic biophysical, pharmacological, and genetic properties of EC cells. We show that EC cells express specific chemosensory receptors, are electrically excitable, and modulate serotonin-sensitive primary afferent nerve fibers via synaptic connections, enabling them to detect and transduce environmental, metabolic, and homeostatic information from the gut directly to the nervous system.

BackgroundIrritable bowel syndrome (IBS) is a chronic gastrointestinal disorder for which no diagnostic tools are currently available. Patients are diagnosed using the Rome IV criteria and subtyped into a diarrhea, constipation, or mixed phenotype based on their dominant stool pattern. A recent development in the biomarker area is the analysis of volatile organic compounds (VOCs). The aim of this study was to evaluate the potential of VOCs as diagnostic and phenotypic biomarkers for IBS in breath and fecal samples.Materials and methodsBreath and fecal samples from IBS patients and healthy asymptomatic controls (HC) were analyzed with multicapillary column/ion mobility spectrometry (MCC/IMS) and classification models were created based upon VOCs and clinical characteristics.DiscussionIrritable bowel syndrome patients were differentiated from HC by means of volatile profiling in both breath and fecal samples with area under the curve (AUCs) of respectively 0.62 and 0.80. Patient subtypes could also be differentiated from each other with AUCs ranging between 0.65 and 0.78. Furthermore, VOC models could differentiate IBS patients based on clinical characteristics like psychological comorbidities and microbiota-influencing therapies.ConclusionThis study is the first to demonstrate the use of VOC profiling with the help of MCC/IMS to differentiate IBS patients. Furthermore, the importance of clinical characteristics beside the dominant stool pattern in the differentiation of IBS patients was emphasized.

Resumen: La pandemia por COVID-19 ha obligado a establecer medidas para evitar los contagios durante la realización de pruebas diagnósticas y terapéuticas en gastroenterología. Los estudios motores del tubo digestivo implican un riesgo elevado e intermedio de trasmisión de la infección por este virus. Dada su indicación electiva o no urgente en la mayoría de los casos, recomendamos diferir la realización de estas pruebas hasta que haya un control significativo de la tasa de infección en cada país, durante la pandemia. Cuando las autoridades sanitarias permitan el regreso a la normalidad y en ausencia de un tratamiento efectivo o una vacuna preventiva de la infección por COVID-19, recomendamos un protocolo estricto para clasificar a los pacientes de acuerdo a su estatus infecto-contagioso mediante el uso apropiado de pruebas para la detección del virus y su respuesta inmune, así como el uso de medidas de protección que deberá seguir el personal de la salud para evitar el contagio durante la realización de una prueba de motilidad gastrointestinal. Abstract: The COVID-19 pandemic has forced the establishment of preventive measures against contagion during the performance of diagnostic and therapeutic tests in gastroenterology. Digestive tract motility tests involve an intermediate and elevated risk for the transmission of COVID-19 infection. Given their elective or non-urgent indication in the majority of cases, we recommend postponing those tests until significant control of the infection rate in each Latin American country has been achieved during the pandemic. When the health authorities allow the return to normality, and in the absence of an effective treatment for or preventive vaccine against COVID-19 infection, we recommend a strict protocol for classifying patients according to their infectious-contagious status through the appropriate use of tests for the detection of the virus and the immune response to it, and the following of protective measures by the healthcare personnel to prevent contagion during the performance of a gastrointestinal motility test.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive and fatal multisystem metabolic disorder. It presents with wide-ranging gastrointestinal and neurologic symptoms. It is caused by a mutation in the TYMP gene which impairs thymidine phosphorylase (TP) activity, therefore leading to the accumulation of thymidine and deoxyuridine in plasma and tissues. Thus, MNGIE can be diagnosed by findings of high levels of thymidine and deoxyuridine. Herein, we present the case of a 40-year-old male who presented with diarrhea, vomiting, and abdominal pain, severe weight loss, neurologic deficits, and distal motor weakness progressing over a period of 13 years. The combination of this broad clinical picture along with results of magnetic resonance imaging, electromyography, colonic biopsies, genetic testing, and elevated plasma and tissue thymidine and deoxyuridine levels confirmed the diagnosis of MNGIE. TYMP gene mutation impairs TP function. TP mutations in the nuclear DNA lead to mitochondrial DNA deletions causing mitochondrial failure and ultimately cell death. Treatment modalities are targeting the restoration of TP activity or aiming to decrease the high levels of thymidine and pyrimide. However, diagnosing this disease is still a challenge and often overdue. This patient’s 13-year delay in diagnosis shows the importance of a complete neurological exam and muscle strength testing in patients with gastrointestinal symptoms. The diagnosis of MNGIE requires interdepartmental collaborative work for diagnosis delay prevention and for optimal patient care.

Patients with oesophageal motility disorders may present with dysphagia, regurgitation or chest pain. High-resolution manometry (HRM) is the current gold-standard modality for the diagnosis of oesophageal motility disorders. The data from HRM are analysed and interpreted to form a diagnosis based on the Chicago classification. However, the Chicago classification is a work in progress, and a few cases can present with features beyond the scope of the current Chicago classification. We present two such cases with distinctive manometric features of an elevated distal contractile integral and increased integrated relaxation pressure but no intrabolus pressurisation or decreased distal latency. As such, they do not fit into any pattern described in the current Chicago classification V.4.0 and can be best described as overlap motility disorders or mixed motor disorders. Patients with such findings warrant further evaluation and long-term follow-up to understand if they evolve to fit into any disorder currently described in the Chicago classification., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

This article offers a framework in history taking for functional gastrointestinal disorders (FGIDs). Clinicians rely on history taking and knowledge of the latest 'Rome IV criteria' rather than biomarkers to make a positive diagnosis of FGIDs. Improving one's history-taking skills is imperative, as early diagnosis can improve patient outcomes by avoiding over investigation and/or chronicity. Our suggested structure for history taking adopts the biopsycho- social model of disease. We describe the assessment of gastrointestinal symptoms with open and closed questions, the importance of ruling out 'alarm' signs or symptoms, the use of a multi-system approach to identify coexisting functional disorders and eliciting patients' nutritional history. We explore the increased psychological comorbidity present in FGIDs and the significance of the social history in identify predisposing, precipitating, perpetuating and protective factors, which will ultimately guide treatment recommendations. We believe history taking should be used to build rapport with patients while, at the same time, validating their problems and reducing stigma. Reattribution of symptoms is then achieved through education of the gut--brain axis and can be used to provide reassurance to patients at the first encounter. Success of treatment depends on engagement and acceptance of such explanations. [ABSTRACT FROM AUTHOR]

Functional gastrointestinal disorders (FGID) are now classified within the Rome IV framework as disorders of gut–brain interaction (DGBI). Disorders of gastrointestinal transit (as defined by abnormalities on contemporary gastrointestinal motility testing) frequently are associated with symptoms that are also characteristic of DGBIs. In this narrative review, we outline a non-inclusive set of systemic diseases or risk factors that have been classically associated with DGBIs and disorders of gastrointestinal transit; these include diabetes mellitus, paraneoplastic syndromes, surgery, Parkinson's disease, systemic sclerosis, endocrinopathies, polypharmacy, and post-infectious syndromes. [ABSTRACT FROM AUTHOR]

Electrical stimulation of the enteric nervous system (ENS) is an attractive approach to modify gastrointestinal transit. Colonic motor complexes (CMCs) occur with a periodic rhythm, but the ability to elicit a premature CMC depends, at least in part, upon the intrinsic refractory properties of the ENS, which are presently unknown. The objectives of this study were to record myoelectric complexes (MCs, the electrical correlates of CMCs) in the smooth muscle and 1) determine the refractory periods of MCs, 2) inform and evaluate closed-loop stimulation to repetitively evoke MCs, and 3) identify stimulation methods to suppress MC propagation. We dissected the colon from male and female C57BL/6 mice, preserving the integrity of intrinsic circuitry while removing the extrinsic nerves, and measured properties of spontaneous and evoked MCs in vitro. Hexamethonium abolished spontaneous and evoked MCs, confirming the necessary involvement of the ENS for electrically evoked MCs. Electrical stimulation reduced the mean interval between evoked and spontaneous CMCs (24.6 ± 3.5 vs. 70.6 ± 15.7 s, P = 0.0002, n = 7). The absolute refractory period was 4.3 s (95% confidence interval (CI) = 2.8–5.7 s, R2 = 0.7315, n = 8). Electrical stimulation applied during fluid distention- evoked MCs led to an arrest of MC propagation, and following stimulation, MC propagation resumed at an increased velocity (n = 9). The timing parameters of electrical stimulation increased the rate of evoked MCs and the duration of entrainment of MCs, and the refractory period provides insight into timing considerations for designing neuromodulation strategies to treat colonic dysmotility. NEW & NOTEWORTHY Maintained physiological distension of the isolated mouse colon induces rhythmic cyclic myoelectric complexes (MCs). MCs evoked repeatedly by closed-loop electrical stimulation entrain MCs more frequently than spontaneously occurring MCs. Electrical stimulation delivered at the onset of a contraction temporarily suppresses the propagation of MC contractions. Controlled electrical stimulation can either evoke MCs or temporarily delay MCs in the isolated mouse colon, depending on timing relative to ongoing activity. [ABSTRACT FROM AUTHOR]

Transition of Care for Adolescents and Young Adults (AYA) with Neurogastroenterology & Motility (NGM) Disorders., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

The brain-gut axis allows bidirectional communication between the central nervous system (CNS) and the enteric nervous system (ENS), linking emotional and cognitive centers of the brain with peripheral intestinal functions. Recent experimental work suggests that the gut microbiota have an impact on the brain-gut axis. A group of experts convened by the International Scientific Association for Probiotics and Prebiotics (ISAPP) discussed the role of gut bacteria on brain functions and the implications for probiotic and prebiotic science. The experts reviewed and discussed current available data on the role of gut microbiota on epithelial cell function, gastrointestinal motility, visceral sensitivity, perception and behavior. Data, mostly gathered from animal studies, suggest interactions of gut microbiota not only with the enteric nervous system but also with the central nervous system via neural, neuroendocrine, neuroimmune and humoral links. Microbial colonization impacts mammalian brain development in early life and subsequent adult behavior. These findings provide novel insights for improved understanding of the potential role of gut microbial communities on psychological disorders, most particularly in the field of psychological comorbidities associated with functional bowel disorders like irritable bowel syndrome (IBS) and should present new opportunity for interventions with pro- and prebiotics.

The enteric nervous system (ENS) is an autonomic “brain-in-the-gut” that integrates gastrointestinal motility, secretion and blood flow into homeostatic patterns of gut behavior. Experimental models for the ENS are the same as for all independent integrative nervous systems, whether in the vertebrate brain and spinal cord or in invertebrate animals. The ENS coordinates and organizes the behavior of the musculature, secretory glands and vascular system, in each of the specialized organs of the gastrointestinal tract, into meaningful behavior of each organ. The ENS stores a library of programs for differing patterns of small and large intestinal adaptive behaviors. Programs in the library are akin to 21st century digital “apps” that run on smart phones, tablet computers and comparable devices.

Purpose: Familial dysautonomia (FD) is a rare hereditary sensory and autonomic neuropathy (HSAN-3) that is clinically characterized by impaired pain and temperature perception and abnormal autonomic function. Patients with FD have gastrointestinal dysmotility and report a range of gastrointestinal symptoms that have yet to be systematically evaluated. The aim of this study was to establish the frequency and severity of gastrointestinal symptoms in patients with FD. Methods: The validated National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS) survey questionnaire, together with additional FD-specific questions, were distributed to 202 living patients with genetically confirmed FD who had been identified from the New York University FD Patient Registry or, when relevant, to their respective caretaker. As a comparison group, we used a general US adult population for whom PROMIS scores were available (N = 71,812). Results: Of the 202 questionnaires distributed, 77 (38%) were returned, of which 53% were completed by the patient. Median age of the respondents was 25 years, and 44% were male. Gastrostomy tube was the sole nutrition route for 25% of the patients, while 53% were reliant on the gastrostomy tube only for liquid intake. The prevalence of gastrointestinal symptoms was significantly higher in each of the eight domains of PROMIS in patients with FD than in the controls. Gastrointestinal symptoms as measured by raw scores on the PROMIS scale were significantly less severe in the FD patient group than in the control population in all domains with the exception of the abdominal pain domain. The surveys completed by caregivers reported the same burden of symptoms as those completed only by patients. Conclusion: Gastrointestinal symptoms affect nearly all patients with FD. Gastrointestinal symptoms are more prevalent in adult patients with FD than in the average US adult population but are less severe in the former. [ABSTRACT FROM AUTHOR]

Background: The Motilis 3D‐Transit system allows ambulatory description of transit patterns throughout the gastrointestinal tract and offers an alternative method for studying gastric motility. We aimed to establish normative values for gastric motility assessed with the method. Method: A total of 132 healthy volunteers ingested the 3D‐Transit capsule for assessment of gastrointestinal transit times. Recordings from 125 subjects were used for definition of normative values. Forty‐six subjects were studied on two consecutive days. Recordings were reanalyzed using newly developed software providing information on gastric emptying (GE) as well as contraction frequency and movement during gastric contractions. Results: The median GE time was 2.7 hours (range 0.1‐21.2). In 89% of subjects, the capsule passed the pylorus within a postingestion period of 6 hours. The median frequency of gastric contractions was 3.1 per minute (range 2.6‐3.8). The frequency was higher in women (3.2, range 2.7‐3.8) than in men (3.0, range 2.6‐3.5) and increased with age (0.004 per year) (P <.05). The median amplitudes were 35° (range 4‐85) when based on rotation of the capsule and 11 mm (range 6‐31) when based on capsule change in position. The rotation amplitude was higher in women and decreased with increasing BMI (P <.05). The position amplitude was also higher in women and increased with the amount of calories in the test meal, but decreased with increasing BMI and age (P <.05). Day‐to‐day variation (P >.05) was considerable while inter‐rater variability was small. Conclusion and Inferences: We have established normative values for gastric motility assessed with the 3D‐Transit system. [ABSTRACT FROM AUTHOR]

There is scarce information on the prevalence of irritable bowel syndrome (IBS) in East Europe. Most countries have small, local studies or studies that to our knowledge are not published in internationally available journals. This is a report from the NeurogastRO 2019 meeting held in Iași, Romania, 7-9 November 2019. During the meeting, specialists from 12 East and Central European countries presented data on IBS epidemiology in their countries. We report the stage of knowledge in each of these countries. [ABSTRACT FROM AUTHOR]

Key points: The vagus nerve has been implicated in mediating behavioural effects of the gut microbiota on the central nervous system. This study examined whether the secretory products of commensal gut bacteria can modulate the excitability of vagal afferent neurons with cell bodies in nodose ganglia.Cysteine proteases from commensal bacteria increased the excitability of vagal afferent neurons via activation of protease‐activated receptor 2 and modulation of the voltage dependence of Na+ conductance activation.Lipopolysaccharide, a component of the cell wall of gram‐negative bacteria, increased the excitability of nodose ganglia neurons via TLR4‐dependent activation of nuclear factor kappa B.Our study identified potential mechanisms by which gut microbiota influences the activity of vagal afferent pathways, which may in turn impact on autonomic reflexes and behaviour. Behavioural studies have implicated vagal afferent neurons as an important component of the microbiota‐gut‐brain axis. However, the mechanisms underlying the ability of the gut microbiota to affect vagal afferent pathways are unclear. We examined the effect of supernatant from a community of 33 commensal gastrointestinal bacterial derived from a healthy human donor (microbial ecosystem therapeutics; MET‐1) on the excitability of mouse vagal afferent neurons. Perforated patch clamp electrophysiology was used to measure the excitability of dissociated nodose ganglion (NG) neurons. NG neuronal excitability was assayed by measuring the amount of current required to elicit an action potential, the rheobase. MET‐1 supernatant increased the excitability of NG neurons by hyperpolarizing the voltage dependence of activation of Na+ conductance. The increase in excitability elicited by MET‐1 supernatant was blocked by the cysteine protease inhibitor E‐64 (30 nm). The protease activated receptor‐2 (PAR2) antagonist (GB 83, 10 μm) also blocked the effect of MET‐1 supernatant on NG neurons. Supernatant from Lactobacillus paracasei 6MRS, a component of MET‐1, recapitulated the effect of MET‐1 supernatant on NG neurons. Lastly, we compared the effects of MET‐1 supernatant and lipopolysaccharide (LPS) from Escherichia coli 05:B5 on NG neuron excitability. LPS increased the excitability of NG neurons in a toll‐like receptor 4 (TLR4)‐dependent and PAR2‐independent manner, whereas the excitatory effects of MET‐1 supernatant were independent of TLR4 activation. Together, our findings suggest that cysteine proteases from commensal bacteria increase the excitability of vagal afferent neurons by the activation of PAR2. Key points: The vagus nerve has been implicated in mediating behavioural effects of the gut microbiota on the central nervous system. This study examined whether the secretory products of commensal gut bacteria can modulate the excitability of vagal afferent neurons with cell bodies in nodose ganglia.Cysteine proteases from commensal bacteria increased the excitability of vagal afferent neurons via activation of protease‐activated receptor 2 and modulation of the voltage dependence of Na+ conductance activation.Lipopolysaccharide, a component of the cell wall of gram‐negative bacteria, increased the excitability of nodose ganglia neurons via TLR4‐dependent activation of nuclear factor kappa B.Our study identified potential mechanisms by which gut microbiota influences the activity of vagal afferent pathways, which may in turn impact on autonomic reflexes and behaviour. [ABSTRACT FROM AUTHOR]

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive and fatal multisystem metabolic disorder. It presents with wide-ranging gastrointestinal and neurologic symptoms. It is caused by a mutation in the TYMP gene which impairs thymidine phosphorylase (TP) activity, therefore leading to the accumulation of thymidine and deoxyuridine in plasma and tissues. Thus, MNGIE can be diagnosed by findings of high levels of thymidine and deoxyuridine. Herein, we present the case of a 40-year-old male who presented with diarrhea, vomiting, and abdominal pain, severe weight loss, neurologic deficits, and distal motor weakness progressing over a period of 13 years. The combination of this broad clinical picture along with results of magnetic resonance imaging, electromyography, colonic biopsies, genetic testing, and elevated plasma and tissue thymidine and deoxyuridine levels confirmed the diagnosis of MNGIE. TYMP gene mutation impairs TP function. TP mutations in the nuclear DNA lead to mitochondrial DNA deletions causing mitochondrial failure and ultimately cell death. Treatment modalities are targeting the restoration of TP activity or aiming to decrease the high levels of thymidine and pyrimide. However, diagnosing this disease is still a challenge and often overdue. This patient's 13-year delay in diagnosis shows the importance of a complete neurological exam and muscle strength testing in patients with gastrointestinal symptoms. The diagnosis of MNGIE requires interdepartmental collaborative work for diagnosis delay prevention and for optimal patient care. [ABSTRACT FROM AUTHOR]

Purpose: Postoperative ileus (POI) is a common complication after abdominal surgery. Invasive stimulation of the cervical vagus nerve is known to reduce inflammatory response and ameliorated POI after surgery in a mouse model. However, the transcutaneous vagus nerve stimulation (tVNS) is a possible non-invasive approach. In this clinical study, we aimed to investigate the effect of tVNS on the activation of the stomach muscle in humans. Methods: Patients requiring open laparotomy were screened for this prospective proof of concept clinical study. After open laparotomy, muscle activity of the stomach was measured by a free running electromyography (EMG) before and during tVNS on the ear. Frequency and amplitude of compound gastric action potentials were the electrophysiological parameters we assessed to reveal the changes in electro motor gastric activity. Gastrin levels as a surrogate marker for vagus nerve activation was analyzed before, 1 and 3 h after tVNS. Results: Fourteen patients were included, no severe adverse events and no medical device related adverse events occurred. tVNS led to significant reduction of action potential frequency and significant elevation of action potential amplitude in the stomach compared to control. Gastrin levels were significantly elevated 3 h after tVNS compared to levels before tVNS. Conclusion: Application of tVNS is a safe and feasible procedure during surgical intervention. Our results provide evidence that tVNS activates efferent visceral vagal fibers. Therefore, this low risk and easy to perform method could be useful to prevent postoperative ileus. Clinical trial register number: DRKS00013340. [ABSTRACT FROM AUTHOR]