Gastrointestinal Motility Disorders Research Articles

Electroacupuncture ameliorates gastrointestinal dysfunction by modulating DMV cholinergic efferent signals to drive the vagus nerve in p-MCAO rats

BackgroundThe use of proton pump inhibitors in the acute phase of cerebral infarction may lead to adverse long-term outcomes, this study aims to explore the potential of electroacupuncture (EA) in replacing omeprazole in exerting post-stroke gastrointestinal protection. MethodsA permanent middle cerebral artery infarction model was established using the modified Longa thread occlusion technique. Gastrointestinal motility, gastrointestinal mucosal damage, cerebral infarct volume, and alterations in choline acetyltransferase (ChAT)-positive neurons within the dorsal motor nucleus of the vagus nerve (DMV) were assessed after 7 days of EA at Zusanli (ST36) or omeprazole intervention. To evaluate the role of the vagal nerve in mitigating post-stroke gastrointestinal dysfunction, we employed subdiaphragmatic vagotomy and the ChAT-specific inhibitor α-NETA. Additionally, we utilized methyllycaconitine (MLA), a selective inhibitor of the α7-type nicotinic acetylcholine receptor (α7nAChR), and PNU282987, an agonist, to identify the target of EA. ResultsEA restored ChAT neurons lost in the DMV, activated the vagus nerve and conferred cerebroprotection while ameliorating gastrointestinal mucosal injury and gastrointestinal motility disorders. In addition, following the administration of the α7nAChR antagonist, the attenuation of gastric mucosal injury and inflammatory factors induced by EA was hindered, although gastrointestinal motility still exhibited improvement. ConclusionEA at ST36 promotes the restoration of cholinergic signaling in the DMV of stroke-afflicted rats, and its excitation of the vagal nerve inhibits gastrointestinal inflammation after stroke via α7nAChR, while improvement in gastrointestinal motility could be mediated by other acetylcholine receptors.

Measurement and Analysis of In Vivo Gastroduodenal Slow Wave Patterns Using Anatomically-Specific Cradles and Electrodes.

Bioelectrical 'slow waves' regulate gastrointestinal contractions. We aimed to confirm whether the pyloric sphincter demarcates slow waves in the intact stomach and duodenum. We developed and validated novel anatomically-specific electrode cradles and analysis techniques which enable high-resolution slow wave mapping across the in vivo gastroduodenal junction. Cradles housed flexible-printed-circuit and custom cradle-specific electrode arrays during acute porcine experiments (N = 9; 44.92 kg ± 8.49 kg) and maintained electrode contact with the gastroduodenal serosa. Simultaneous gastric and duodenal slow waves were filtered independently after determining suitable organ-specific filters. Validated algorithms calculated slow wave propagation patterns and quantitative descriptions. Butterworth filters, with cut-off frequencies (0.0167 - 2) Hz and (0.167 - 3.33) Hz, were optimal filters for gastric and intestinal slow wave signals, respectively. Antral slow waves had a frequency of (2.76 ± 0.37) cpm, velocity of (4.83 ± 0.21) mm·s-1, and amplitude of (1.13 ± 0.24) mV, before terminating at the quiescent pylorus that was (46.54 ± 5.73) mm wide. Duodenal slow waves had a frequency of (18.13 ± 0.56) cpm, velocity of (11.66 ± 1.36) mm·s-1, amplitude of (0.32 ± 0.03) mV, and originated from a pacemaker region (7.24 ± 4.70) mm distal to the quiescent zone. Novel engineering methods enable measurement of in vivo electrical activity across the gastroduodenal junction and provide qualitative and quantitative definitions of slow wave activity. The pylorus is a clinical target for a range of gastrointestinal motility disorders and this work may inform diagnostic and treatment practices.

Mesenchymal cells regulate enteric neural crest cell migration via RET-GFRA1b trans-signaling

During early development, the enteric nervous system forms from the migration of enteric neural crest cells (ENCCs) from the foregut to the hindgut, where they undergo proliferation and differentiation facilitated by interactions with enteric mesenchymal cells (EMCs). This study investigates the impact on ENCC migration of EMC-ENCC communication mediated by GFRA1b expressed in EMCs. GFRA1-expressing cells in day 11–12 (E11–12) mouse embryos differentiated into smooth muscle cells from E12 onwards. Observations at E12–13.5 revealed high levels of GFRA1 expression on the anti-mesenteric side of the hindgut, correlating with enhanced ENCC migration. This indicates that GFRA1 in EMCs plays a role in ENCC migration during development. Examining GFRA1 isoforms, we found high levels of GFRA1b, which lacks amino acids 140–144, in EMCs. To assess the impact of GFRA1 isoforms on EMC-ENCC communication, we conducted neurosphere drop assays. This revealed that GFRA1b-expressing cells promoted GDNF-dependent extension and increased neurite density in ENCC neurospheres. Co-culture of ENCC mimetic cells expressing RET and GFRA1a with EMC mimetic cells expressing GFRA1a, GFRA1b, or vector alone showed that only GFRA1b-expressing co-cultured cells sustained RET phosphorylation in ENCC-mimetic cells for over 120 min upon GDNF stimulation. Our study provides evidence that GFRA1b-mediated cell-to-cell communication plays a critical role in ENCC motility in enteric nervous system development. These findings contribute to understanding the cellular interactions and signaling mechanisms that underlie enteric nervous system formation and highlight potential therapeutic targets for gastrointestinal motility disorders.

Хронічна інтестинальна псевдообструкція в дітей (огляд літератури)

Hirschsprung disease and chronic intestinal pseudo-obstruction (CIPO) in children are the most common and severe disorders of gastro-intestinal tract motility. While the problems connected with the Hirschsprung disease widely coverage in native literature, the publications that devoted the CIPO absent. Aim of the study was to analyze the literature data that devoted to the diagnosis and treatment of children with CIPO. Intestinal pseudo-obstruction refers to heterogeneous groups of disorders with a similar phenotypic presentation characterized by obstructive intestinal symptoms in the absence of true anatomical obstruction. CIPO classification based on the primary dysfunction: affected enteral nervous system (neuropathy), affected smooth muscle (myopathy) or interstitial cells Cajal (mesenchymopathy). Besides that, the intestinal pseudo-obstruction is divided into primary and secondary, congenital and acquired, total and segmentary. The main clinical features, methods of investigation in suspected CIPO such as radiological (roentgenography and roentgenoscopy, computed tomography, cine magnetic resonance), endoscopic, manometry, pathohistological, etc. were listed. The main principles of nutrition support, conventional therapy, and surgical management were presented. Conclusions. CIPO is a severe disorder of gastrointestinal motility that caused by various factors, which can be congenital and/or acquired. Diagnosis of CIPO based on the results of clinical, instrumental, and pathohistological investigation. The management of children with CIPO should include nutritional support, conventional therapy, and, for the clear indices, surgical correction. No conflict of interests was declared by the authors.

Domperidone inhibits cell proliferation via targeting MEK and CDK4 in esophageal squamous cell carcinoma

BackgroundEsophageal squamous cell carcinoma (ESCC) is one of the leading causes of digestive system tumor related death in the world. Unfortunately, effective chemopreventive agent is lack for patients with ESCC in clinical practice, which leads to the extremely high mortality rate.MethodsA library of prescribed drugs was screened for finding critical anti-tumor properties in ESCC cells. The phosphoproteomics, kinase array, pulldown assay and drug affinity responsive target stabilization assay (DARTS) were applied to explore mechanisms and searched for synergistic targets. Established models of PDX in mice were used to determine the therapeutic effect of domperidone.ResultsAfter screening a library of prescribed drugs, we discovered that domperidone has anti-tumor properties. Domperidone, acting as a gastroprokinetic agent, has been widely used in clinic for gastrointestinal motility disorders. Despite limited research, there are indications that domperidone may have anti-tumor properties. In this study, we determined that domperidone significantly inhibited ESCC proliferation in vitro and in vivo. We employed phosphoproteomics to reveal p-ERK, and p-SMAD3 down-regulation upon domperidone treatment. Then, the results of kinase assay and pulldown assay further validated that domperidone directly combined with MEK1/2 and CDK4, leading to the inhibition of their kinase activity. Furthermore, our results revealed that MEK/ERK and CDK4/SMAD3 signal pathway were major pathways in domperidone against ESCC.ConclusionCollectively, these findings suggest that domperidone serves as an effective “multi-target” inhibitor of MEK1/2 and CDK4, offering potential benefits for the chemoprevention of ESCC.

Got the Munchies for an Egg Sandwich? The Effects of Cannabis on Bowel Motility and Beyond.

The use of medicinal cannabis has a long history dating back thousands of years. Recent discoveries have shed light on its mechanism of action with the identification of cannabinoid receptors and endocannabinoids, which make up the body's endocannabinoid system. Cannabinoid receptors, particularly the cannabinoid 1 and 2 receptors, play a crucial role in modulating the gut-brain axis and serve as potential therapeutic targets for gastrointestinal motility and inflammatory disorders. With increasing legalization of cannabis and a rising number of users, understanding the effects of cannabis on gut motility is essential for nuclear medicine providers. Although tetrahydrocannabinol, the principal psychoactive constituent of cannabis, may decrease gut motility in experimental settings, it appears to paradoxically improve symptoms in gastroparesis. Treatment effects are difficult to measure given the large number of variables that could significantly alter outcomes, such as cannabinoid type, potency, and route of intake. Another consideration is the highly personalized gut microbiome, which directly interacts with the endocannabinoid system. Further research is required to delineate these multifaceted, complex cannabinoid interactions. The goal of this article is to explore the knowns and unknowns of the impact of cannabis on the alimentary system.

The Effects of Short- and Long-Term Ingestion of Plastic Toxin Bisphenol A on Gastrointestinal Transit Time in Rats.

Introduction Exposure to bisphenol A (BPA), a toxic chemical released from plastic, affects various body functions, including reproduction, metabolism, and development. The most common route of exposure to BPA is oral, and the gastrointestinal(GI) tract is, therefore, the first body system to be exposed to BPA. BPA has been well-documented to impair gut contractility in rats, in vitro. It may therefore be hypothesized that BPA may adversely affect GI motility and hence slow down the movement of food, resulting in the increased transit of food bolus in the GI tract. There are no reports so far on the effects of BPA on GI transit time. Objectives The present study was undertaken to examine the impact of exposure to BPA by a single oral dose (termed as short-term ingestion of BPA) and chronic (28-day) oral dose (termed as long-term ingestion of BPA) on the transit time of food bolus in the gut of adult male albino rats. Methods and materials The study was conducted in the Department of Physiology,Institute of MedicalSciences,Banaras Hindu University, Varanasi,Uttar Pradesh, India. In one set of experiments, each animal was fed a food pellet, once (short-term ingestion) containing BPA (2 µg/kg and 50 µg/kg in different groups), and in another set of experiments, each animal was fed a food pellet containing BPA (50 µg/kg/day) for 28 consecutive days (long-term ingestion). Control rats in both sets were fed food pellets without BPA. Subsequently, the gastric transit index (GTI), ileocecal transit index (ICTI), and colonic transit time (CTT) were determined by the standard charcoal marker method. Results One-time ingestion of a food pellet containing BPA caused a significant (p < 0.05) drop in the GTI and ICTI and an increase in the CTT with both doses of BPA (2 and 50 µg/kg). Similarly, after chronic (28-day), oral BPA exposure, a significant decrease in the GTI and ICTT and an increase in CTT were observed. Conclusion Both short-term (one-time) and long-term (28-day) oral exposure to BPA-containing food harmed GI transit. Slow GI transit may lead to metabolic disorders and GI motility disorders, such as constipation.

Gastrointestinal dysmotility in rodent models of Parkinson's disease.

Multiple studies describe prodromal, nonmotor dysfunctions that affect the quality of life of patients who subsequently develop Parkinson's disease (PD). These prodromal dysfunctions comprise a wide array of autonomic issues, including severe gastrointestinal (GI) motility disorders such as dysphagia, delayed gastric emptying, and chronic constipation. Indeed, strong evidence from studies in humans and animal models suggests that the GI tract and its neural, mainly vagal, connection to the central nervous system (CNS) could have a major role in the etiology of PD. In fact, misfolded α-synuclein aggregates that form Lewy bodies and neurites, i.e., the histological hallmarks of PD, are detected in the enteric nervous system (ENS) before clinical diagnosis of PD. The aim of the present review is to provide novel insights into the pathogenesis of GI dysmotility in PD, focusing our attention on functional, neurochemical, and molecular alterations in animal models.

Serping1 associated with α-synuclein increase in colonic smooth muscles of MPTP-induced Parkinson’s disease mice

Patients with Parkinson’s disease (PD) have gastrointestinal motility disorders, which are common non-motor symptoms. However, the reasons for these motility disorders remain unclear. Increased alpha-synuclein (α-syn) is considered an important factor in peristalsis dysfunction in colonic smooth muscles in patients with PD. In this study, the morphological changes and association between serping1 and α-syn were investigated in the colon of the 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine-induced chronic PD model. Increased serping1 and α-syn were noted in the colon of the PD model, and decreased serping1 also induced a decrease in α-syn in C2C12 cells. Serping1 is a major regulator of physiological processes in the kallikrein-kinin system, controlling processes including inflammation and vasodilation. The kinin system also comprises bradykinin and bradykinin receptor 1. The factors related to the kallikrein-kinin system, bradykinin, and bradykinin receptor 1 were regulated by serping1 in C2C12 cells. The expression levels of bradykinin and bradykinin receptor 1, modulated by serping1 also increased in the colon of the PD model. These results suggest that the regulation of increased serping1 could alleviate Lewy-type α-synucleinopathy, a characteristic of PD. Furthermore, this study could have a positive effect on the early stages of PD progression because of the perception that α-syn in colonic tissues is present prior to the development of PD motor symptoms.

Profile of interstitial cells of Cajal in a murine model of chagasic megacolon.

Disorders of gastrointestinal motility are the major physiologic problem in chagasic megacolon. The contraction mechanism is complex and controlled by different cell types such as enteric neurons, smooth muscle, telocytes, and an important pacemaker of the intestine, the interstitial cells of Cajal (ICCs). The role of ICCs in the progression of acute and chronic Chagas disease remains unclear. In the present work, we investigate the aspects of ICCs in a long-term model of Chagas disease that mimics the pathological aspects of human megacolon. Different subsets of ICCs isolated from Auerbach's myenteric plexuses and muscle layers of control and Trypanosoma cruzi infected animals were determined by analysis of CD117, CD44, and CD34 expression by flow cytometer. Compared with the respective controls, the results showed a reduced frequency of mature ICCs in the acute phase and three months after infection. These results demonstrate for the first time the phenotypic distribution of ICCs associated with functional dysfunction in a murine model of chagasic megacolon. This murine model proved valuable for studying the profile of ICCs as an integrative system in the gut and as a platform for understanding the mechanism of chagasic megacolon development.

The first study appraising colonic diverticulosis and Helicobacter pylori diagnosed by histopathology.

Colonic diverticulosis might be caused by low-fiber dietary habits, gastrointestinal motility disorders, and colonic wall resistance changes, which might also affect the upper gastrointestinal system mucosa. Therefore, the present study aims to answer whether the gastric histopathological findings of the cases with diverge from those without. This retrospective cross-sectional study included 184 cases who underwent both upper and lower gastrointestinal endoscopy procedures between January 2020 and December 2022. Notably, 84 cases were colonic diverticulosis, while the rest of the study group was control. Their demographic, laboratory, and histopathological findings were compared meticulously. The median ages for the colonic diverticulosis and control were 67.07±8.14 and 66.29±15.83 years, respectively, and no statistical difference concerning the age and gender distribution between them was recognized. The median levels of white blood cells, neutrophils, glucose, creatinine, and aspartate aminotransferase in colonic diverticulosis were significantly increased compared to control. As for pathological comparison, colonic diverticulosis had a higher prevalence of Helicobacter pylori (45.2 vs. 38%), while atrophy and intestinal metaplasia prevalence were nearly the same in the groups, without significance regarding Helicobacter pylori. Consequently, colonic diverticulosis should not be overlooked, particularly when the abovementioned laboratory parameters are augmented in a dyspeptic patient. A correlation might be raised between Helicobacter pylori and colonic diverticulosis. Eradication therapy might help attenuate the risk of colonic diverticulosis when Helicobacter pylori has emerged in a patient.

The association between oral carbohydrate intake before orthopedic surgery for osteoporotic fractures and outcomes in elderly patients

BackgroundOral carbohydrate (CHO) intake is a safe method with effective clinical results in various surgical patients before surgery. Nevertheless, due to a lack of adequate clinical data, it is not frequently utilized in older patients undergoing orthopedic surgery for osteoporotic fractures (OPFs), especially in China. The purpose of the present study was to examine the relationship between preoperative oral CHO consumption and outcomes in elderly patients undergoing surgical treatment for OPFs.MethodsThis retrospective cohort study was conducted at a single Chinese institution and included a total of 879 elderly patients (median age: 71 years; range: 50–99 years) who underwent OPF surgery. Various exclusion criteria were established as follows: (a) the necessity for urgent surgical intervention; (b) the existence of hypoglycemia, hyperglycemia, or diabetes mellitus with blood glucose levels lower than 2.8 mmol/L; (c) a medical history of gastrointestinal motility disorders or delayed gastric emptying; (d) the utilization of local anesthesia; (e) a Charlson comorbidity index (CCI) score over 2; and (f) an American Society of Anesthesiologists (ASA) score exceeding 3. After propensity score (PS) matching, 264 patients from each cohort were included in the analysis. The primary outcome was the all-cause mortality rate within 60 days post-surgery, while secondary outcomes included the length of hospital stay (LOS), hospitalization costs, intraoperative and postoperative blood transfusions, and the incidence of postoperative nausea and vomiting (PONV) and aspiration. The relationship between preoperative oral CHO intake and outcomes was evaluated using multivariate regression analysis.ResultsAfter PS matching, preoperative oral CHO intake was negatively associated with 60-day mortality in the fully adjusted model (odds ratio 0.35; 95% confidence interval 0.12–0.97; P-value: 0.04). Patients who received preoperative oral CHO intake also had a shorter LOS and lower hospitalization costs than those who did not receive CHO intake. However, none of the models showed a significant association between CHO intake and PONV or blood transfusion risk. Furthermore, no cases of aspiration were observed in either cohort.ConclusionsPreoperative oral CHO intake may be associated with reduced mortality risk and improved outcomes in elderly patients undergoing surgical treatment for OPFs. However, it is important to acknowledge the limitations of our study, including its retrospective nature, potential unmeasured confounding variables, the small sample size, incomplete data on important variables such as duration of surgery and inflammatory markers, and the limited generalizability due to the participation of only one institution. Future research with larger sample sizes and a broader range of events is warranted to validate and enhance the validity of our findings, particularly in assessing long-term results and understanding the underlying mechanisms.

Patterns of diet‐related practices and symptoms of gastroesophageal reflux among high school students: A cross‐sectional study

Background: GERD is a gastrointestinal motility disorder characterized by the reflux of gastric contents into the esophagus, causing typical symptoms such as heartburn (a burning sensation in the epigastric region), acid regurgitation (a bitter taste in the mouth), nausea, and dysphagia, which can lead to esophageal mucosal damage. Over the long term, it can result in complications like Barrett's esophagus. The prevalence of GERD in Asia was approximately 2.5%-7.8% in 2014, generally lower compared to Western countries. However, recent data indicates an increasing prevalence. Poor dietary patterns, such as irregular eating habits, consuming low-nutrient foods, excessive or insufficient food intake, can elevate gastric acid production and affect an individual's health.Purpose: To determine the relationship between dietary patterns and symptoms of Gastroesophageal Reflux Disease (GERD) among vocational high school students.Method: A quantitative study was applied using correlation analysis with a cross-sectional study approach. The research was conducted at Vocational High School Bojonegoro in January 2023. The study population comprised 305 students in grade 12. The sampling technique employed was purposive sampling, with a sample size of 74 respondents. The measurement tool for dietary pattern variables was the FFQ questionnaire, and GERD symptoms were assessed using the GERD-Q questionnaire. Data analysis techniques included univariate analysis to describe the frequency distribution of each variable and bivariate analysis using the chi-square test to determine the relationship between dietary patterns and GERD symptoms among students.Results: Poor dietary patterns were found to cause GERD in 47 (97.9%) respondents, whereas good dietary patterns significantly minimized GERD; only 1 (2.1%) respondent experienced GERD symptoms in this study. The research resulted a value of ρ = 0.000 &lt; α (0.05), indicating that the ρ value in this study was less than α (0.05) or below 0.05; thus, H0 was rejected. It can be concluded that there is a relationship between dietary patterns and GERD symptoms, with a correlation coefficient value of 0.542 (moderate) and a positive correlation direction.Conclusion: There is a significant relationship between dietary patterns and GERD symptoms. The correlation coefficient analysis also showed a figure of 0.542 (moderate) with a positive correlation direction, indicating that better dietary patterns lead to fewer respondents suffering from GERD.Suggestion: It is advisable for students to avoid consuming spicy foods, fast food, fried food, and high-sugar food or beverages. They should pay more attention to a balanced diet and timely meals. Additionally, the school authorities are encouraged to establish regulations or advisories to cafeteria owners to refrain from providing fast food, nutritionally poor food, carbonated drinks, spicy food, and other items that may contribute to digestive problems among students.

Bidirectional regulation effect of rhubarb as laxative and astringent by metabolomics studies

Ethnopharmacological relevanceRhubarb, a prominent traditional Chinese medicine, has been employed as a potent laxative for centuries and garnered particular popularity among the youth owing to its notable efficacy in weight management. Historical records indicated that rhubarb initially exhibited robust laxative properties, but extended and consistent usage may lead to an astringent response in the later stage of long-term use. In contrast, steamed pieces of rhubarb (SR), preparing through the process of steaming with wine, have demonstrated a gentle laxative effect with no reported adverse effects. Aim of the studyOur study was designed to explore the intricate mechanisms underlying laxative and astringent properties of rhubarb through metabolomics research. Materials and methodsIn this investigation, we employed a serum metabolomics approach utilizing the UPLC-Q-Extractive-Orbitrap-MS method to delve into the contrasting laxative and astringent effects of rhubarb, as well as to unravel the mechanisms of underpinning its bidirectional regulatory influence. To commence, we assessed alterations in Evacuation Index (EI) values, intestinal hormone levels, and colon histopathology in mice to gauge rhubarb's laxative and astringent effects. Subsequently, metabolomics methodology was employed for cluster analysis through Principal Component Analysis (PCA) and biomarker identification via Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA). Then, we delved into the distinctions in characteristic biomarkers, metabolic pathways, their association with pathological changes, and correlation heatmap for biomarkers between raw pieces of rhubarb (RR) and SR to gain insights into the potential mechanisms behind rhubarb's bidirectional regulatory effects. ResultsOur findings revealed that RR exhibited a laxative effect in the early stage and transitioned to an astringent effect in the later stage, as indicated by the EI values. In contrast, SR consistently demonstrated a mild laxative effect. Biochemical indexes and histopathological assessments unveiled that RR triggered its astringent effect by inhibiting secretion of motilin (MTL), promoting secretion of vasoactive intestinal peptide (VIP) and epinephrine (EPI), and inducing onset of inflammation. Furthermore, serum metabolomics analysis identified 59 discriminative biomarkers modulated by RR and SR. Through comprehensive analysis, we elucidated the in vivo transformation relationships among multiple endogenous metabolites. Notably, our results underscored the down-regulation of certain phosphatidylcholines (PCs), amino acids, acylcarnitines, and up-regulation of lysophosphatidylcholines (LysoPCs) played pivotal roles in the onset of gut dysfunction, intestinal inflammation, gut barrier damage, and gastrointestinal motility disorder upon prolonging RR administration, ultimately contributing to its astringent effect. Additionally, our correlation analysis elucidated that anthraquinones, stilbenes, and phenylbutanones were the pharmacodynamic material basis responsible for inducing the astringent effect of RR. ConclusionThis study provides valuable insights into the bidirectional regulatory effects of rhubarb and sheds light on its underlying mechanisms through a comprehensive metabolomics approach.

Gastrointestinal dysmotility complicating Behçet's syndrome: description of a newly recognised clinical phenotype.

Gastrointestinal dysmotility may arise in a variety of auto-immune and auto-inflammatory diseases and hitherto has not been described in Behçet's syndrome (BS). We present data on a cohort of seven patients under our care who presented with symptoms of and investigations compatible with an immune associated disorder of gastrointestinal motility, or enteric neuropathy. We describe the clinical features and investigation results. We undertook a trial of a novel treatment in the disease, apheresis, and noted a response not only to the enteric neuropathy but also to the systemic features of the disease, despite previous maximal immunosuppressive therapy in most cases. Gastrointestinal dysmotility may arise in BS and is effectively treated by apheresis. The mechanism by which this response is made immunologically requires to be elucidated in future studies.

L-Fucose promotes enteric nervous system regeneration in type 1 diabetic mice by inhibiting SMAD2 signaling pathway in enteric neural precursor cells

BackgroundDiabetes can lead to extensive damage to the enteric nervous system (ENS), causing gastrointestinal motility disorders. However, there is currently a lack of effective treatments for diabetes-induced ENS damage. Enteric neural precursor cells (ENPCs) closely regulate the structural and functional integrity of the ENS. L-Fucose, is a dietary sugar that has been showed to effectively ameliorate central nervous system injuries, but its potential for ameliorating ENS damage and the involvement of ENPCs in this process remains uncertain.MethodsGenetically engineered mice were generated for lineage tracing of ENPCs in vivo. Using diabetic mice in vivo and high glucose-treated primary ENPCs in vitro, the effects of L-Fucose on the injured ENS and ENPCs was evaluated by assessing gastrointestinal motility, ENS structure, and the differentiation of ENPCs. The key signaling pathways in regulating neurogenesis and neural precursor cells properties, transforming growth factor-β (TGF-β) and its downstream signaling pathways were further examined to clarify the potential mechanism of L-Fucose on the injured ENS and ENPCs.ResultsL-Fucose improved gastrointestinal motility in diabetic mice, including increased defecation frequency (p < 0.05), reduced total gastrointestinal transmission time (p < 0.001) and bead expulsion time (p < 0.05), as well as enhanced spontaneous contractility and electric field stimulation-induced contraction response in isolated colonic muscle strips (p < 0.001). The decrease in the number of neurons and glial cells in the ENS of diabetic mice were reversed by L-Fucose treatment. More importantly, L-Fucose treatment significantly promoted the proportion of ENPCs differentiated into neurons and glial cells both in vitro and in vivo, accompanied by inhibiting SMAD2 phosphorylation.ConclusionsL-Fucose could promote neurogenesis and gliogenesis derived from ENPCs by inhibiting the SMAD2 signaling, thus facilitating ENS regeneration and gastrointestinal motility recovery in type 1 diabetic mice.7Zzihak_jncvcnfCNwCPXsVideo

Prebiotic prevents the development of gastrointestinal motility disorders caused by omeprazole

The synthetic disaccharide lactulose, consisting of fructose and galactose, after oral administration in an unchanged form reaches the lower part of the gastrointestinal tract, where under the action of normal flora it is broken down into short-chain fatty acids that stimulate colon motility. The effect of lactulose on gastrointestinal tract motility in the conditions of its long-term suppression by omeprazole has not been investigated. We studied the influence of lactulose on spontaneous and carbachol-stimulated gastric and colonic motility in rats treated with omeprazole for 28 days. The animals were divided into 3 groups. The first group of animals served as a control. The animals in the second group were administered omeprazole intraperitoneally at a dose of 14 mg/kg orally once a day for 28 days. The animals in the third group were simultaneously injected intraperitoneally with omeprazole and prebiotic lactulose at a dose of 0.2 g/kg orally once a day for 28 days. On the day after the last injections of drugs, we investigated the spontaneous and carbachol-stimulated contractions in the stomach and colon by the balloon graphic method. It was found that the frequency of spontaneous and stimulated contractions in the stomach and colon did not change significantly after 28 days of omeprazole treatment. The amplitude and index of spontaneous and carbachol-stimulated contractions in the stomach and colon were significantly weaker compared to the control. One day after the 28-day simultaneous administration of omeprazole and lactulose the amplitude and index of spontaneous and stimulated contractions in the stomach and colon increased compared with the group of rats treated with omeprazole alone. We concluded that the positive effect of lactulose on gastric and colon motility is a result of the prebiotic properties of lactulose which leads to the normalization of the microbiocenosis in the gastrointestinal tract and the elimination of the inflammatory process in it.

Macrophage regulation of the "second brain": CD163 intestinal macrophages interact with inhibitory interneurons to regulate colonic motility - evidence from the Cx3cr1-Dtr rat model.

Intestinal macrophages are well-studied for their conventional roles in the immune response against pathogens and protecting the gut from chronic inflammation. However, these macrophages may also have additional functional roles in gastrointestinal motility under typical conditions. This is likely to occur via both direct and indirect influences on gastrointestinal motility through interaction with myenteric neurons that contribute to the gut-brain axis, but this mechanism is yet to be properly characterised. The CX3CR1 chemokine receptor is expressed in the majority of intestinal macrophages, so we used a conditional knockout Cx3cr1-Dtr (diphtheria toxin receptor) rat model to transiently ablate these cells. We then utilized ex vivo video imaging to evaluate colonic motility. Our previous studies in brain suggested that Cx3cr1-expressing cells repopulate by 7 days after depletion in this model, so we performed our experiments at both the 48 hr (macrophage depletion) and 7-day (macrophage repopulation) time points. We also investigated whether inhibitory neuronal input driven by nitric oxide from the enteric nervous system is required for the regulation of colonic motility by intestinal macrophages. Our results demonstrated that CD163-positive resident intestinal macrophages are important in regulating colonic motility in the absence of this major inhibitory neuronal input. In addition, we show that intestinal macrophages are indispensable in maintaining a healthy intestinal structure. Our study provides a novel understanding of the interplay between the enteric nervous system and intestinal macrophages in colonic motility. We highlight intestinal macrophages as a potential therapeutic target for gastrointestinal motility disorders when inhibitory neuronal input is suppressed.

Risk factors for catheter-related bloodstream infections associated with home parental nutrition in children with intestinal failure: A prospective cohort study

Catheter-related bloodstream infection (CRBSI) is the most common, potentially life-threatening complication of long-term parenteral nutrition (PN). We prospectively assessed the incidence and risk factors for CRBSI in children receiving long-term home PN (HPN) for intestinal failure (IF) in a single IF rehabilitation center. Data regarding episodes and potential risk factors for CRBSI in children on HPN were prospectively recorded. Forty-one of 75 children were diagnosed with CRBSI. The overall CRBSI rate was 1.61 per 1000 catheter days. The indications for HPN were gastrointestinal motility disorders in 35%, short bowel syndrome (SBS) in 28% graft versus host disease (GvHD) post bone marrow transplant in 17%, congenital enteropathy in 15%, and severe neurodevelopmental impairment in 5%. Gastrointestinal motility disorders had significantly higher CRBSI rate compared to other groups (p<0.0005; 2.74 in motility group vs 1.54 in GvHD group vs 0.52 in congenital enteropathies vs 0.36 in SBS group vs 0.67 in severe neurodevelopmental delay). Multivariate analysis revealed that enterocutaneous distal stoma (ileostomy or colostomy) (HR 3.35 [95% CI, 1.63-6.86]; p<0.001), age <2 years (HR 0.28 [95% CI, 0.15-0.53]; p<0.0001), male sex (HR 2.28 [95% CI, 1.51-3.43]; p<0.0001), non-use of taurolidine citrate lock (HR 2.70 [95% CI, 1.72-4.11]; p<0.0001) and gastrointestinal motility disorder (HR 3.02 [95% CI, 1.81-4.91]; p<0.001) were independent risk factors for developing CRBSI. Extra care in managing PN connections and disconnections should be taken in children with an underlying gastrointestinal motility disorder, distal enterocutaneous stoma, male sex and those aged <2 years since they are at a significantly higher risk of CRBSI. Early introduction of taurolidine lock should be considered.

Effect and mechanism of needleless transcutaneous neuromodulation on gastrointestinal function after pancreaticoduodenectomy

Background Gastrointestinal motility disorders tend to develop after pancreaticoduodenectomy (PD). The objectives of this study were: (1) to investigate the impact of needleless transcutaneous neuromodulation (TN) on the postoperative recuperation following pancreaticoduodenectomy (PD), and (2) to explore the underlying mechanisms by which TN facilitates the recovery of gastrointestinal function after PD. Methods A total of 41 patients scheduled for PD were randomized into two groups: the TN group (n = 21) and the Sham-TN group (n = 20). TN was performed at acupoints ST-36 and PC-6 twice daily for 1 h from the postoperative day 1 (POD1) to day 7. Sham-TN was performed at non-acupoints. Subsequent assessments incorporated both heart rate variation and dynamic electrogastrography to quantify alterations in vagal activity (HF) and gastric pacing activity. Results 1)TN significantly decreased the duration of the first passage of flatus (p < 0.001) and defecation (p < 0.01) as well as the time required to resume diet (p < 0.001) when compared to sham-TN;2)Compared with sham-TN, TN increased the proportion of regular gastric pacing activity (p < 0.01);3) From POD1 to POD7, there was a discernible augmentation in HF induced by TN stimulation(p < 0.01);4) TN significantly decreased serum IL-6 levels from POD1 to POD7 (p < 0.001);5) TN was an independent predictor of shortened hospital stay(β = − 0.349, p = 0.035). Conclusion Needleless TN accelerates the recovery of gastrointestinal function and reduces the risk of delayed gastric emptying in patients after PD by enhancing vagal activity and controlling the inflammatory response.