Disorders of gut-brain interaction through the lens of polyvagal theory.

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.

A systematic cognitive behavioral therapy approach for pediatric disorders of gut-brain interaction.

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.

Pediatric to adult transition care in neurogastroenterology and motility: A position paper from the American Neurogastroenterology and Motility Society and European Society of Neurogastroenterology and Motility.

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.

Treating disorders of brain-gut interaction with multidisciplinary integrated care. Moving towards a new standard of care.

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.

"An urgent need for transition of care programs for adolescents and young adults with neurogastroenterology and motility disorders".

Transition of Care for Adolescents and Young Adults (AYA) with Neurogastroenterology & Motility (NGM) Disorders.

The Functional Implications of Transanal Irrigation: Insights from Pathophysiology and Clinical Studies of Neurogenic Bowel Dysfunction.

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.

Three-Dimensional Fractal Analysis of the Interstitial Cells of Cajal Networks of Gastrointestinal Tissue Specimens.

Introduction: Several functional gastrointestinal disorders (FGIDs) have been associated with the degradation or remodeling of the network of interstitial cells of Cajal (ICC). Introducing fractal analysis to the field of gastroenterology as a promising data analytics approach to extract key structural characteristics that may provide insightful features for machine learning applications in disease diagnostics. Fractal geometry has advantages over several physically based parameters (or classical metrics) for analysis of intricate and complex microstructures that could be applied to ICC networks. Methods: In this study, three fractal structural parameters: Fractal Dimension, Lacunarity, and Succolarity were employed to characterize scale-invariant complexity, heterogeneity, and anisotropy; respectively of three types of gastric ICC network structures from a flat-mount transgenic mouse stomach. Results: The Fractal Dimension of ICC in the longitudinal muscle layer was found to be significantly lower than ICC in the myenteric plexus and circumferential muscle in the proximal, and distal antrum, respectively (both p < 0.0001). Conversely, the Lacunarity parameters for ICC-LM and ICC-CM were found to be significantly higher than ICC-MP in the proximal and in the distal antrum, respectively (both p < 0.0001). The Succolarity measures of ICC-LM network in the aboral direction were found to be consistently higher in the proximal than in the distal antrum (p < 0.05). Conclusions: The fractal parameters presented here could go beyond the limitation of classical metrics to provide better understanding of the structural-functional relationship between ICC networks and the conduction of gastric bioelectrical slow waves.

Persistent and newly developed gastrointestinal symptoms after surgery for intestinal malrotation in children: Dysmotility or disorders of gut and brain interaction?

OBJECTIVES: Surgery for intestinal malrotation (IM) aims to correct the defect and improve symptoms; however, many have persistent gastrointestinal (GI) symptoms postoperatively. We evaluated the incidence, clinical presentation, and long-term outcomes of children with surgically repaired IM and its possible association with disorders of gut and brain interaction (DGBI). METHODS: Multicenter retrospective study was conducted in patients from 0 to 21 years old, who had surgery for IM from 2000 to 2021 across three pediatric tertiary care centers. Data analyzed included demographics, time to diagnosis, idiopathic diagnosis, incidental diagnosis, postoperative follow-up, surgical time, and the need for surgery including bowel detorsion. Outcome variables were the presence of postoperative GI symptoms and DGBIs, and overall resolution of symptoms. We also evaluated the potential association of demographics and other included variables with our outcome variables. RESULTS: Ninety-two patients with surgically corrected IM were included, 54% were male, and median age of diagnosis and surgical correction was 4.9 and 7.8 months, respectively. Median follow-up after surgery was 64 months. A total of 77% had postoperative GI symptoms, and notably, 78% of patients without symptoms before surgery (incidental diagnosis) developed GI symptoms postoperatively and 27% of patients met Rome IV criteria for a one or more DGBI. No factors were associated to the presence of postoperative symptoms or DGBIs in multivariate analysis. Female gender was the only factor associated with lack of resolution of symptoms at follow-up. CONCLUSION: Pediatric IM is commonly associated with postoperative GI symptoms and DGBI well beyond surgery. An increased awareness about the prevalence of DGBI in these patients may help reach a prompt and accurate diagnosis, and improve their quality of life.

Bowel perforation and anal ventriculoperitoneal shunt migration: A systematic review.

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.

Practical multidisciplinary framework for the assessment and management of patients with unexplained chronic aerodigestive symptoms.

OBJECTIVE: Patients experiencing unexplained chronic throat symptoms (UCTS) are frequently referred to gastroenterology and otolaryngology outpatient departments for investigation. Often despite extensive investigations, an identifiable structural abnormality to account for the symptoms is not found. The objective of this article is to provide a concise appraisal of the evidence-base for current approaches to the assessment and management of UCTS, their clinical outcomes, and related healthcare utilisation. DESIGN: This multidisciplinary review critically examines the current understanding of aetiological theories and pathophysiological drivers in UCTS and summarises the evidence base underpinning various diagnostic and management approaches. RESULTS: The evidence gathered from the review suggests that single-specialty approaches to UCTS inadequately capture the substantial heterogeneity and pervasive overlaps among clinical features and biopsychosocial factors and suggests a more unified approach is needed. CONCLUSION: Drawing on contemporary insights from the gastrointestinal literature for disorders of gut-brain interaction, this article proposes a refreshed interdisciplinary approach characterised by a positive diagnosis framework and patient-centred therapeutic model. The overarching aim of this approach is to improve patient outcomes and foster collaborative research efforts.

The Brain-Gut Clinic in Hospital Universiti Sains Malaysia: Pioneering New Service to Advance Neuro-Gastroenterology and Motility in Malaysia.

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.

The consequences of limited training in disorders of gut-brain interaction: Results from a national survey of gastroenterology trainees in the United Kingdom.

BACKGROUND: Despite their high prevalence and burden, disorders of gut-brain interaction (DGBI) are undertaught and underrepresented in medical curricula. We evaluated the exposure of UK gastroenterology trainees to DGBI and their comfort managing these conditions. METHODS: An electronic survey was distributed to trainees via UK training program directors. The survey included questions on stage of training; subspecialty interest; access to DGBI training opportunities, and comfort levels with DGBI diagnosis and management. Responses were compared between junior and senior trainees, by subspecialty interest (luminal and non-luminal), by geographical region, and training program size. KEY RESULTS: One hundred twelve trainees from across the UK participated (21.4% of national training post holders). Exposure to DGBI lectures (32.8% junior vs. 73.3% senior trainees, p = 0.00003) and clinics (9.0% junior vs. 42.2% senior trainees, p = 0.00003), increased with seniority. Regardless of seniority, most trainees were rarely comfortable making a DGBI diagnosis (39.5% senior vs. 33.9% junior trainees, p = 0.69), and were not comfortable initiating neuromodulators (50% senior vs. 25.8% junior trainees, p = 0.08). Trainees without a luminal subspecialty interest (50%) accessed fewer DGBI clinics (p = 0.04), had less communication skills training (p = 0.04) and were less likely to have been observed during DGBI consultations (p = 0.002). Responses were similar across UK regions and did not differ between smaller and larger programs. CONCLUSIONS & INFERENCES: DGBI training opportunities are limited in UK gastroenterology training across training grades. Most trainees lack confidence with DGBI diagnosis and management. Urgent interventions need to be targeted at all stages of training to ensure DGBI competencies for future gastroenterologists and improve patient outcomes.

Clinical utility of colonic low-amplitude propagating contractions in children with functional constipation.

BACKGROUND: Colonic high-amplitude propagating contractions (HAPC) are generally accepted as a marker of neuromuscular integrity. Little is known about low-amplitude propagating contractions (LAPCs); we evaluated their clinical utility in children. METHODS: Retrospective review of children with functional constipation undergoing low-resolution colon manometry (CM) recording HAPCs and LAPCs (physiologic or bisacodyl-induced) in three groups: constipation, antegrade colonic enemas (ACE), and ileostomy. Outcome (therapy response) was compared to LAPCs in all patients and within groups. We evaluated LAPCs as potentially representing failed HAPCs. KEY RESULTS: A total of 445 patients were included (median age 9.0 years, 54% female), 73 had LAPCs. We found no association between LAPCs and outcome (all patients, p = 0.121), corroborated by logistic regression and excluding HAPCs. We found an association between physiologic LAPCs and outcome that disappears when excluding HAPCs or controlling with logistic regression. We found no association between outcome and bisacodyl-induced LAPCs or LAPC propagation. We found an association between LAPCs and outcome only in the constipation group that cancels with logistic regression and excluding HAPCs (p = 0.026, 0.062, and 0.243, respectively). We found a higher proportion of patients with LAPCs amongst those with absent or abnormally propagated (absent or partially propagated) HAPCs compared to those with fully propagated HAPCs (p = 0.001 and 0.004, respectively) suggesting LAPCs may represent failed HAPCs. CONCLUSIONS/INFERENCES: LAPCs do not seem to have added clinical significance in pediatric functional constipation; CM interpretation could rely primarily on the presence of HAPCs. LAPCs may represent failed HAPCs. Larger studies are needed to further validate these findings.

Constipation in transverse myelitis.

Transverse myelitis is an extremely rare neuroinflammatory disorder. About half of the affected patients develop paraplegia associated with urinary and bowel dysfunction. The bowel dysfunction is thought to be benign and is usually managed with dietary management and laxatives. We report a case of a man in his 60s presenting with transverse myelitis and the acute disease course complicated with treatment refractory intestinal dysfunction resulting in intestinal perforation, eventually leading to his death. Thus, this case helps us weigh the fact that intestinal dysfunction in the case of transverse myelitis is not always benign but can lead to deadly outcomes as well.

Allergen-free extracts from birch, ragweed, and hazel pollen activate human and guinea-pig submucous and spinal sensory neurons.

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.

Curricular representation of neurogastroenterology: A survey among medical students in Germany.

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.