Neurogastroenterology and Motility最新文献

Background: Intestinal muscularis resident macrophages (MMφ) are a specialized subset of tissue macrophages involved in local inflammatory regulation. Although sympathetic nerves are anatomically associated with MMφ, the mechanisms underlying their interaction remain unclear. This study aimed to elucidate the role of adrenergic receptor signaling in modulating MMφ activation during lipopolysaccharide (LPS)-induced inflammation.

Methods: MMφ were isolated from mouse intestinal muscularis for receptor profiling. The macrophage-like cell line J774.1 was stimulated with LPS, with or without adrenergic modulators. LPS-treated intestinal segments were examined ex vivo under electrical stimulation with sympathetic or β-adrenergic blockade. Macrophage activation was assessed by measuring nitric oxide (NO) production and iNOS mRNA expression.

Key results: MMφ isolated from mouse muscularis expressed α₁, α₂, β₁, and β₂ adrenergic receptors. In J774.1 cells, LPS significantly increased NO production. Activation of α₁, β₁, or β₂ receptors attenuated this response, whereas α₂ activation enhanced it. Norepinephrine similarly suppressed LPS-induced NO increase, and this suppression was reversed by β₁/β₂ antagonists. Inhibition of adenylate cyclase also reversed the NO suppression induced by a non-selective β receptor agonist. In intestinal segments, LPS-induced iNOS expression was not altered by electrical stimulation, but was significantly enhanced when stimulation was combined with non-selective β or β₁ antagonists.

Conclusions and inferences: Our results suggest that norepinephrine released from sympathetic nerves suppresses inflammation via activation of β₁ and β₂ receptors on MMφ. These findings advance the understanding of neuroimmune interactions underlying gastrointestinal homeostasis and its disruption during inflammatory states.

Background: Diarrhea remains a significant global health burden, necessitating the discovery of safer and more effective therapeutic agents. Schaftoside (SCF), a bioactive flavonoid, has demonstrated diverse pharmacological properties, though its anti-diarrheal potential remains underexplored. This study aimed to evaluate the anti-diarrheal activity of SCF and elucidate its underlying mechanisms.

Methods: The in vivo efficacy of SCF was assessed in a castor oil-induced diarrhea model using 2-day-old chicks. Animals were pretreated orally with SCF (5, 10, 20 mg/kg), loperamide (3 mg/kg), or bismuth subsalicylate (10 mg/kg). Diarrheal parameters, including latency period, stool frequency, and secretion weight, were recorded. Complementary in silico molecular docking was performed to investigate SCF's binding affinity (BA) and interactions with the μ-opioid receptor (PDB ID: 8EFB), cyclooxygenase-1 (COX-1; 6Y3L), and cyclooxygenase-2 (COX-2; 5F19).

Results: SCF administration produced a significant, dose-dependent anti-diarrheal effect. The highest dose (20 mg/kg) markedly reduced diarrheal secretion and stool frequency while prolonging the onset of diarrhea, with efficacy comparable to standard drugs. In silico analysis revealed strong binding affinities of SCF for the μ-opioid receptor (-9.8 kcal/mol) and COX-2 (-9.0 kcal/mol), supported by multiple hydrogen bond and hydrophobic interactions with key active-site residues.

Conclusion: These findings demonstrate that SCF possesses substantial anti-diarrheal activity, potentially mediated through dual modulation of the μ-opioid receptor and COX-2 pathways. SCF represents a promising natural candidate for further development as a therapeutic agent for diarrhea management.

Introduction: A subgroup of treated achalasia patients has recurrent symptoms which prompt consideration of additional treatment. The aim of this study was to examine the additional yield of functional lumen imaging probe (FLIP) to high-resolution manometry (HRM) and timed barium esophagram (TBE) in selection of patients for retreatment.

Methods: This prospective observational cohort study was performed between November 2019 and October 2025 and included treated achalasia patients with recurrent or persistent symptoms who underwent FLIP in addition to HRM and TBE prior to retreatment. The primary outcome was the association between the distensibility index measured by FLIP and response to retreatment (treatment success: Eckardt score ≤ 3).

Results: In total 84 patients were included (median age 50 years, 36.9% female). At a median follow-up of 11 weeks after retreatment, 82.1% had treatment success (N = 69/84) and 17.9% had treatment failure (N = 15/84). The distensibility index at 40 mL on FLIP did not significantly differ between patients with and without treatment success (1.4 mm²/mmHg vs. 1.0 mm²/mmHg, p = 0.463). Almost all patients with abnormal HRM and TBE results had treatment success (N = 22/23, 95.7%). In cases with inconclusive HRM and TBE results, treatment success was 83.3% when FLIP results were normal (N = 10/12) and 74.3% when FLIP results were abnormal (N = 26/35).

Conclusion: FLIP did not provide added value over HRM and TBE for identifying treated achalasia patients who may benefit from further treatment. The difficulty in selecting achalasia patients for retreatment highlights the complexity of this patient population and underscores the need for further research.

Background: Infant colic is a frequent and distressing disorder of early infancy. The Rome IV criteria define colic as occurring from birth until 5 months of age, although emerging evidence suggests that symptoms may persist beyond this threshold. This study aimed to determine the prevalence of infant colic beyond 5 months and evaluate whether the Rome IV diagnostic age cutoff accurately reflects the clinical course of the disorder.

Methods: We conducted a cross-sectional, multicenter study across four regions of Colombia during the. Caregivers of infants aged 1-12 months were recruited from general pediatrics and pediatric gastroenterology outpatient clinics. Infant colic was diagnosed using the validated Spanish version of the Rome IV Questionnaire on Pediatric Gastrointestinal Symptoms (QPGS-IV). Demographic data were analyzed descriptively, and comparisons between age groups (1-4 months vs. 5-12 months) were performed using Fisher's exact test.

Key results: A total of 1236 infants were included. Twenty-one (1.7%) met symptomatic Rome IV criteria for infant colic. Prevalence was 3.0% (18/600) at 1-4 months and 0.5% (3/636) at 5-12 months (p < 0.001). No significant differences were found by sex (p = 0.39) or prematurity (p = 0.26). Fourteen percent of all colic cases occurred beyond 5 months, and none beyond 8 months of age.

Conclusions and inferences: Infant colic was common during early infancy but rare beyond 5 months, confirming that the Rome IV cutoff reflects the typical clinical course for most infants. However, a small subgroup with persistent symptoms beyond 5 months suggests that the current time boundary may not encompass the full spectrum of infant colic.

Background: Cholinergic neuromuscular transmission is central to gastrointestinal (GI) motility and is traditionally attributed to calcium-dependent, vesicular acetylcholine (ACh) release from enteric neurons. However, non-quantal, calcium-independent mechanisms-possibly involving transporter-mediated ACh efflux-may also contribute to cholinergic signaling.

Aim: To investigate both classical and alternative mechanisms of ACh release in the colon, focusing on the potential role of non-vesicular, transporter-dependent pathways in modulating smooth muscle contractility.

Methods: Experiments were performed on full-thickness and epithelium-depleted rat colonic muscle strips. Neostigmine, a reversible acetylcholinesterase inhibitor, was used to enhance cholinergic mechanisms. A panel of pharmacological agents-including tetrodotoxin (TTX selective blocker of Na⁺ channels), ω-conotoxin GVIA (Ca²⁺ N-type channel blocker), Hemicholinium (choline transporter inhibitor), corticosterone (OCTs inhibitor), and hexamethonium (nicotinic receptor antagonist)-was applied to differentiate neural, non-neural, and transporter-mediated contributions to ACh release.

Key results: Neostigmine-induced contractions were preserved in epithelium-depleted strips, following neural blockade with TTX and ω-conotoxin GVIA. Hemicholinium concentration-dependently attenuated these contractions, suggesting involvement of high-affinity choline transporters operating in reverse mode. In contrast, corticosterone and hexamethonium had negligible effects, arguing against substantial roles for OCTs and nicotinic transmission.

Conclusions and inferences: These findings support the existence of a non-vesicular, transporter-dependent cholinergic signaling mechanism in the colon. This alternative pathway may contribute to the regulation of colonic motility and represents a novel target in GI motility modulation.

Background and aims: Cognitive behavioral therapy (CBT) is an effective but underutilized treatment for bowel disorders of gut-brain interaction (DGBI). We aimed to examine attitudes and perceptions toward CBT in adults with and without bowel DGBI or other gastrointestinal (GI) diseases.

Methods: We conducted an online survey on perceptions and experiences related to CBT. Presence of bowel DGBI was determined using Rome IV criteria. Responses were compared across individuals with bowel DGBI, other GI diseases, and controls, and between individuals with different types of bowel DGBI including irritable bowel syndrome (IBS), functional constipation (FC), and functional diarrhea (FDr). Associations between psychosocial factors and perceptions of CBT were examined.

Results: Of 770 participants (268 with bowel DGBI), 70.2% reported CBT could be helpful. Barriers included lack of trained professionals, cost, and time or effort. Participants with bowel DGBI were more familiar with CBT (OR = 1.72, p < 0.001), but no more likely to have been offered CBT than controls. Those with other GI diseases had 4.3-times higher odds of having been offered CBT. Attitudes toward providers recommending CBT and overall receptiveness to CBT did not differ among groups. Non-White, non-Black individuals were less likely to perceive CBT as helpful (OR = 0.61, p = 0.01), while Black participants were more willing to try CBT (OR = 1.73, p = 0.003). Participants with FDr were more likely to report CBT could be helpful than those with IBS (OR = 2.62, p = 0.035).

Conclusions: Despite similar perceptions, patients with bowel DGBI are less frequently referred for CBT than those with other non-DGBI GI diseases. Sociocultural differences may also influence beliefs. Strategies for access expansion, early referrals, and culturally competent care will be essential for effectively integrating CBT into bowel DGBI management.

Background: Patients with gastroparesis (Gp) can have a variety of symptoms. Apart from use of prokinetics, symptomatic therapies for the predominant symptom (PrS) are used.

Aims: (1) To classify Gp patients based on their PrS; (2) To determine differences in Gp symptoms, gastric emptying (GE), quality of life (QOL), treatments, and symptom improvement among Gp patients with different PrS.

Methods: Gp patients were enrolled in a multicenter registry and followed for 96-weeks. Patients recorded their PrS and completed questionnaires assessing symptoms and QOL at enrollment and at follow up visits.

Results: Of 1013 Gp patients (361 diabetic, 607 idiopathic, 45 post-fundoplication), the PrS were nausea (31%), vomiting (20%), abdominal pain (20%), bloating (9%), fullness (4%), GERD (4%), constipation (3%). Abdominal pain was more often a PrS in idiopathics, whereas vomiting was more often a PrS in diabetics. QOL scores were lower in the abdominal pain PrS group. PrS was associated with greater use of directed symptomatic treatment (antiemetic agents and gastric electrical stimulation for nausea and vomiting, prokinetic agents for vomiting and fullness, and constipation medications for constipation). Of 555 patients followed over 48 weeks, GCSI improved by ≥ 1 in 26% overall, more often in patients with initial PrS of nausea (32%) and bloating (35%) and less often for initial PrS of fullness (13%) or abdominal pain (15%).

Conclusions: In Gp patients, the most common PrS were nausea, vomiting, and abdominal pain. PrS is associated with QOL, treatments utilized, and patient outcomes. Thus, the PrS of a patient with Gp provides useful information about their present condition and future outcome.

Background: Functional dyspepsia (FD) is a disorder of gut-brain interaction (DGBI), while gastroparesis (GP) is a motility disorder with overlapping upper gastrointestinal symptoms, including epigastric pain, postprandial fullness, early satiation, nausea, and vomiting, although their relative prevalence differs between conditions. First-line therapies, such as proton pump inhibitors and Helicobacter pylori eradication, often provide limited relief, prompting interest in alternative, mechanism-based treatments.

Aim: To review the literature on the use of predominantly central and predominantly peripheral neuromodulators in FD and GP and to develop a symptom-directed therapeutic framework.

Methods: We conducted a comprehensive review of the literature, synthesizing data from randomized controlled trials, observational studies, and clinical guidelines. Pharmacological profiles, pathophysiological targets, and safety considerations were evaluated.

Results: Predominantly central neuromodulators, particularly tricyclic antidepressants (TCA) and mirtazapine, are effective in reducing visceral hypersensitivity and are most appropriate for epigastric pain syndrome (EPS). Predominantly peripheral neuromodulators-including prokinetic agents such as metoclopramide, domperidone, levosulpiride, cinitapride, prucalopride, and itopride-are beneficial in postprandial distress syndrome (PDS) and GP, especially for nausea and early satiation. Treatment selection should be individualized according to the predominant symptom profile, considering drug receptor specificity, safety, psychiatric comorbidities, and cardiovascular risk.

Conclusion: Neuromodulators provide a rational, mechanism-based treatment option for FD and GP, and a symptom-oriented approach may optimize patient outcomes; although high-quality, subtype-specific trials are needed to strengthen the evidence base.

Background: Irritable bowel syndrome (IBS) is a highly prevalent disorder of gut-brain interaction best understood within a biopsychosocial framework. Recent studies in other healthcare systems have suggested racial disparities in the management of IBS.

Aims: We aimed to investigate racial disparities in the diagnosis and management of IBS including adherence to national guidelines between White British and Ethnic minority patients with IBS in a UK secondary care setting.

Methods: Consecutive Ethnic minority patients (N = 68) with a coded secondary care diagnosis of IBS at a gastroenterology department in a large UK teaching hospital were identified from electronic health records. Data on diagnostic pathways and access to treatments and adherence to national guidelines were compared statistically with an equal number of age and gender matched white British controls (N = 68).

Results: Compared to age and gender matched White British controls, Ethnic Minority patients saw more clinicians (p = 0.012) and required more outpatient appointments to make an IBS diagnosis (p = 0.007). There were disparities identified in the approach to treatment, with ethnic minority patients less likely to be recommended second-line pharmacological treatment (p = 0.004) and Brain-Gut Behavioral Therapies (p = 0.005) compared to their White British counterparts. Across both groups, adherence to national guidelines in the diagnostic approach and treatment for IBS was low, with most patients not being recommended second-line medical, dietary, or behavioral treatment for their IBS.

Conclusions: These data suggest that the management of IBS in secondary care in the UK has not kept pace with advances in evidence-based treatments and updated guidelines. Moreover, racial disparities, whether influenced by clinicians or patients, were seen between the two ethnic groups regarding the diagnosis and management of IBS. Further studies are necessary to determine the barriers contributing to these disparities, to influence future interventions and clinical training to address them.

Background: Limited research has evaluated national medical expenditures associated with pediatric disorders of gut-brain interaction (DGBI), despite the high prevalence of these disorders in children and their association with reduced quality of life.

Methods: We used data from the 2017-2022 Medical Expenditure Panel Survey (MEPS) to estimate the individual- and national-level outpatient, office-based, prescribed medication, emergency room, inpatient, and other medical expenditures, and overall expenditures associated with pediatric DGBI. Pediatric DGBI included International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10) codes associated with irritable bowel syndrome, functional dyspepsia, and other functional intestinal disorders (including constipation) among 40,067 individuals ≤ 18 years receiving medical care in the United States.

Key results: After controlling for predisposing factors, enabling resources, and co-morbid medical conditions, total per patient annual medical expenditures were $5217 (in 2022 dollars) for pediatric patients with DGBI-an estimate that was $2587 greater than the estimated medical expenditures for children without DGBI. Incremental spending from DGBI patients versus patients without DGBI was highest for outpatient visits followed by office-based visits, prescribed medications, and emergency room visits. Total annual medical expenditures for pediatric patients with DGBI were estimated at $2.08 billion.

Conclusions and inferences: The results illuminate the significant national medical expenditures associated with pediatric DGBI, suggesting the potential importance of early detection and effective treatment for pediatric DGBI and the need for future research to improve assessment and evidence-based treatment for pediatric DGBI.