Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’...Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’s disease.In this review,we summarize the changes in short-chain fatty acid levels and the abundance of short-chain fatty acid-producing bacteria in various samples from patients with Parkinson’s disease,highlighting the critical role of gut homeostasis imbalance in the pathogenesis and progression of the disease.Focusing on the nervous system,we discuss the molecular mechanisms by which short-chain fatty acids influence the homeostasis of both the enteric nervous system and the central nervous system.We identify key processes,including the activation of G protein-coupled receptors and the inhibition of histone deacetylases by short-chain fatty acids.Importantly,structural or functional disruptions in the enteric nervous system mediated by these fatty acids may lead to abnormalα-synuclein expression and gastrointestinal dysmotility,which could serve as an initiating event in Parkinson’s disease.Furthermore,we propose that short-chain fatty acids help establish communication between the enteric nervous system and the central nervous system via the vagal nerve,immune circulation,and endocrine signaling.This communication may shed light on their potential role in the transmission ofα-synuclein from the gut to the brain.Finally,we elucidate novel treatment strategies for Parkinson’s disease that target short-chain fatty acids and examine the challenges associated with translating short-chain fatty acid-based therapies into clinical practice.In conclusion,this review emphasizes the pivotal role of short-chain fatty acids in regulating gut-brain axis integrity and their significance in the pathogenesis of Parkinson’s disease from the perspective of the nervous system.Moreover,it highlights the potential value of short-chain fatty acids in early intervention for Parkinson’s disease.Future research into the molecular mechanisms of short-chain fatty acids and their synergistic interactions with other gut metabolites is likely to advance the clinical translation of innovative short-chain fatty acid-based therapies for Parkinson’s disease.展开更多
Objective:Diabetes-induced gastrointestinal(GI)motility disorders are increasingly prevalent.Damage to the enteric nervous system(ENS),composed primarily of enteric neurons and glial cells,is an essential mechanism in...Objective:Diabetes-induced gastrointestinal(GI)motility disorders are increasingly prevalent.Damage to the enteric nervous system(ENS),composed primarily of enteric neurons and glial cells,is an essential mechanism involved in these disorders.Although electroacupuncture(EA)has shown the potential to mitigate enteric neuronal loss,its mechanism is not fully understood.Additionally,the effects of EA on enteric glial cells have not been investigated.Enteric neural precursor cells(ENPCs)contribute to the structural and functional integrity of the ENS,yet whether EA enhances their differentiation into enteric neurons and glial cells remains unexplored.This study investigates whether EA promotes ENS repair through enhancing ENPC-derived neurogenesis and gliogenesis and elucidates the potential molecular mechanisms involved.Methods:Transgenic mice were used to trace Nestin+/nerve growth factor receptor(Ngfr)+ENPCs labeled with green fluorescent protein(GFP)in vivo.Mice were randomly divided into four groups:control,diabetes mellitus(DM),DM+sham EA,and DM+EA.The effects of EA on diabetic mice were evaluated by GI motility,ENS structure,and ENPC differentiation.Glial cell line-derived neurotrophic factor(GDNF)/Ret signaling was detected to clarify the underlying molecular mechanisms.Results:EA alleviated diabetes-induced GI motility disorders,as indicated by reduced whole gut transit time,shortened colonic bead expulsion time,and enhanced smooth muscle contractility.Furthermore,EA attenuated diabetes-induced losses of enteric neurons and glial cells,thereby restoring ENS integrity.Notably,EA reversed the diabetes-induced decrease in ENPCs and significantly increased the absolute number and the proportion of ENPC-derived enteric neurons.However,immunofluorescence analyses revealed no colocalization between EA-induced glial fibrillary acidic protein+glial cells and GFPlabeled ENPCs.Mechanistically,GDNF/Ret signaling was elevated in intestinal tissues and upregulated in ENPCs in EA-treated diabetic mice.Conclusion:EA facilitates ENS repair by promoting Nestin+/Ngfr+ENPC differentiation into enteric neurons via upregulation of GDNF/Ret signaling,and driving enteric gliogenesis from non-Nestin+/Ngfr+ENPCs.These findings highlight EA's role in ameliorating diabetes-induced GI dysmotility through ENPC-derived ENS restoration.展开更多
Rationale:Enteric fever is a major public health problem in developing and underdeveloped counties.Extraintestinal manifestations in typhoid are estimated in 27%cases and are associated with severe and complicated dis...Rationale:Enteric fever is a major public health problem in developing and underdeveloped counties.Extraintestinal manifestations in typhoid are estimated in 27%cases and are associated with severe and complicated diseases.Patients concerns:We report three cases of enteric fever with rare extra intestinal manifestations.Diagnoses:Enteric fever with acute motor-sensory axonal neuropathy,enteric fever with myocarditis,and enteric fever with splenic vein thrombosis.Interventions:All patients were treated with antibiotics.Additionally,Patient 1 was treated with桇immunoglobulin;Patient 2 was treated with vasopressors and anti-cardiac remodeling drugs like ramipril and metoprolol;Patient 3 was treated with anticoagulation with low molecular weight heparin.Outcomes:All patients improved clinically and were followed up on outpatient.Lessons:The diagnosis of enteric fever is challenging and there is an urgent need for prompt-targeted management for better outcomes.Especially in endemic zones and in non-endemic zones as a disease of emporiatric significance.展开更多
BACKGROUND Colonic anastomotic leakage(AL)remains a feared complication of colorectal surgery.Usually,a defunctioning stoma or a proximal colostomy is performed to reduce the AL rate but cannot completely prevent AL.M...BACKGROUND Colonic anastomotic leakage(AL)remains a feared complication of colorectal surgery.Usually,a defunctioning stoma or a proximal colostomy is performed to reduce the AL rate but cannot completely prevent AL.Moreover,defunctioning colostomy is associated with high morbidity.This study assessed the feasibility of completely preventing colonic AL using total enteric flow diversion without a defunctioning stoma in a pig model of colonic AL.AIM To determine the feasibility of preventing colonic AL via total enteric flow diversion in pigs.METHODS A total of 14 pigs underwent surgery to create colon anaesthesia with severe defects for establishing the AL model.The pigs were then randomized into the control group(n=7),which received no further therapy,and a diversion group(n=7),which underwent placement of a modified ileostomy tube to divert the enteric contents from the colon externally.The general condition,serum Creactive protein level,white blood cell count,5-day incidence of colon AL,and development of abdominal abscesses were evaluated.RESULTS A modified ileostomy tube with a balloon was placed and pressurized to 20 kPa at a distance of 10-20 cm proximal to the ileocecal valve,effectively obstructing the intestine without causing injury and efficiently diverting the enteric contents.In the diversion group,no cases of peritonitis or abscess were observed.In contrast,all pigs in the control group developed either abdominal abscesses or peritonitis.CONCLUSION Instead of ileostomy or colostomy,the total enteric flow diversion technique with the placement of a modified ileostomy tube and balloon in the ileum can effectively or completely prevent colon AL.展开更多
BACKGROUND Environmental enteric dysfunction(EED)is a subclinical condition caused by fecal-oral contamination leading to enteric inflammation and dysbiosis.Bile acids serve to facilitate lipid digestion and absorptio...BACKGROUND Environmental enteric dysfunction(EED)is a subclinical condition caused by fecal-oral contamination leading to enteric inflammation and dysbiosis.Bile acids serve to facilitate lipid digestion and absorption,regulate metabolic pathways associated with childhood growth and inflammation,and may be affected by EED.AIM To investigate bile acid metabolism in Bangladeshi children with EED and its association with growth impairment.METHODS We conducted a cross-sectional study of 100 Bangladeshi infants(aged 6-9 months)and quantified serum and fecal bile acids using LC-MS/MS.We compared profiles to a control group of 6 American children(6-12 months)and 80 older Bangladeshi children(aged 2 years).RESULTS Bangladeshi infants had higher levels of plasma unconjugated primary(65.23%vs 44.25%,P=0.003)and sulfated primary bile acids(12.98%vs<0.001%,P=0.01),with lower primary conjugated bile acids(0.69%vs 2.74%,P≤0.001)compared to American children.Stool unconjugated primary bile acids were inversely associated with weight-for-age[regression coefficient(β)=-0.01,P=0.01]and height-for-age Z scores(β=-0.01,P=0.03).Conjugated secondary bile acids were inversely associated with small intestine bacterial overgrowth(β=-1096.68,P=0.05).Fecal myeloperoxidase was associated with sulfated secondary bile acids(β=-0.40,P=0.04).Compared to 2-year-old children,the Bangladeshi infant’s serum had higher levels of unconjugated primary bile acids(65.23%vs 9.20%,P≤0.001)and lower levels of primary conjugated bile acids(0.69%vs 80.38%,P≤0.001).CONCLUSION Our data suggests an age-dependent defect in conjugation of primary bile acids in Bangladeshi children with compensatory hydrophilic shunting.Additionally,bile acid profiles are associated with intestinal overgrowth.展开更多
[Objectives]To explore the mechanism of action of Tongxieyaofang ultrafine granular powder in treating visceral hypersensitivity in rats with diarrhea-predominant irritable bowel syndrome(IBS-D)based on enteric glial ...[Objectives]To explore the mechanism of action of Tongxieyaofang ultrafine granular powder in treating visceral hypersensitivity in rats with diarrhea-predominant irritable bowel syndrome(IBS-D)based on enteric glial cells(EGCs).[Methods]Eighty-four healthy male Wistar rats of SPF grade were selected and randomly assigned to seven groups,each comprising 12 rats:a normal control group,a model control group,a traditional Tongxieyaofang granular powder group(4.060 g/kg),three Tongxieyaofang ultrafine granular powder groups at low,medium,and high doses(1.015,2.030,and 4.060 g/kg of raw drug,respectively),and a pinaverium bromide group(0.018 g/kg).With the exception of the normal control group,all other groups were subjected to an IBS-D visceral hypersensitivity sensitivity model in rats developed by the chronic water avoidance stress method.Three days post modeling,the rats received continuous oral gavage administration for 8 d.Following the treatment period,serum and colon tissue samples were collected from each group.The BDNF level in the serum was quantified using ELISA.Additionally,the protein expression levels of GFAP,BDNF,and TrkB in colon tissues were assessed via Western blot assay.[Results]Compared to the normal control group,the serum BDNF levels in the model control group were significantly elevated(P<0.01).In contrast,each treatment group exhibited a significant reduction in serum BDNF levels relative to the model control group(P<0.01).Furthermore,the protein expression levels of GFAP,BDNF,and TrkB in colon tissue were significantly higher in the model control group compared to the normal control group(P<0.05,P<0.01).Conversely,these protein expressions were significantly decreased in each treatment group compared to the model control group(P<0.05,P<0.01).[Conclusions]Tongxieyaofang ultrafine granular powder effectively alleviates visceral sensitivity in IBS-D rats and inhibits the activation of EGCs,speculating that its mechanism of action involves the suppression of abnormal EGC activation.展开更多
Clostridioides difficile(C.difficile)is the most common pathogen causing health care-associated infections.C.difficile TcdA and TcdB have been shown to activate enteric neurons;however,what population of these cells i...Clostridioides difficile(C.difficile)is the most common pathogen causing health care-associated infections.C.difficile TcdA and TcdB have been shown to activate enteric neurons;however,what population of these cells is more profoundly influenced and the mechanism underlying these effects remain unknown.AIM To characterize a specific population of TcdA-affected myenteric neurons and investigate the role of the P2X7 receptor in TcdA-induced ileal inflammation,cell death,and the changes in the enteric nervous system in mice.METHODS Swiss mice were used to model TcdA-induced ileitis in ileal loops exposed to TcdA(50μg/Loop)for 4 h.To investigate the role of the P2X7 receptor,Brilliant Blue G(50 mg/kg,i.p.),which is a nonspecific P2X7 receptor antagonist,or A438079(0.7μg/mouse,i.p.),which is a competitive P2X7 receptor antagonist,were injected one hour prior to TcdA challenge.Ileal samples were collected to analyze the expression of the P2X7 receptor(by quantitative real-time polymerase chain reaction and immunohistochemistry),the population of myenteric enteric neurons(immunofluorescence),histological damage,intestinal inflammation,cell death(terminal deoxynucleotidyltransferasemediated dUTP-biotin nick end labeling),neuronal loss,and S100B synthesis(immunohistochemistry).RESULTS TcdA upregulated(P<0.05)the expression of the P2X7 receptor gene in the ileal tissues,increasing the level of this receptor in myenteric neurons compared to that in control mice.Comparison with the control mice indicated that TcdA promoted(P<0.05)the loss of myenteric calretinin+(Calr)and choline acetyltransferase+neurons and increased the number of nitrergic+and Calr+neurons expressing the P2X7 receptor.Blockade of the P2X7 receptor decreased TcdAinduced intestinal damage,cytokine release[interleukin(IL)-1β,IL-6,IL-8,and tumor necrosis factor-α],cell death,enteric neuron loss,and S100B synthesis in the mouse ileum.CONCLUSION Our findings demonstrated that TcdA induced the upregulation of the P2X7 receptor,which promoted enteric neuron loss,S100B synthesis,tissue damage,inflammation,and cell death in the mouse ileum.These findings contribute to the future directions in understanding the mechanism involved in intestinal dysfunction reported in patients after C.difficile infection.展开更多
Through investigating ten recreational marine beaches in China, we aimed to detect the occurrence of human enteric viruses in coastal bathing beaches and find a correlationship, if any, between the presence of enteric...Through investigating ten recreational marine beaches in China, we aimed to detect the occurrence of human enteric viruses in coastal bathing beaches and find a correlationship, if any, between the presence of enteric viruses in surface seawater and the concentrations of fecal coliforms, the conventional indicator of fecal pollution. In this study, twenty seawater samples were assayed for fecal coliforms and human pathogenic enteric viruses （hepatitis A viruses, rotaviruses, polioviruses） analysis. Enteric viruses were detected by RT-PCR, in 20 sample sites, 5%, 40%, 40% were positive for the presence of human hepatitis A viruses, rotaviruses, polioviruses, respectively. Seven of 20 sites are suffering from severe fecal contamination, based on traditional plate counts of fecal coliform outnumbering the established thresholds for recreation. Additionally, statistical analysis presented that no correlation was found between bacterial indicators and viruses in surface seawaters. The data confirmed that indicator bacteria in water are not reflective of the presence of enteric viruses in marine waters. Thus, current recreational water quality standards of both bacterial and viral indices should be reevaluated.展开更多
Diabetes,commonly known for its metabolic effects,also critically affects the enteric nervous system(ENS),which is essential in regulating gastrointestinal(GI)motility,secretion,and absorption.The development of diabe...Diabetes,commonly known for its metabolic effects,also critically affects the enteric nervous system(ENS),which is essential in regulating gastrointestinal(GI)motility,secretion,and absorption.The development of diabetes-induced enteric neuropathy can lead to various GI dysfunctions,such as gastroparesis and irregular bowel habits,primarily due to disruptions in the function of neuronal and glial cells within the ENS,as well as oxidative stress and inflammation.This editorial explores the pathophysiological mechanisms underlying the development of enteric neuropathy in diabetic patients.Additionally,it discusses the latest advances in diagnostic approaches,emphasizing the need for early detection and intervention to mitigate GI complications in diabetic individuals.The editorial also reviews current and emerging therapeutic strategies,focusing on pharmacological treatments,dietary management,and potential neuromodulatory interventions.Ultimately,this editorial highlights the necessity of a multidisciplinary approach in managing enteric neuropathy in diabetes,aiming to enhance patient quality of life and address a frequently overlooked complication of this widespread disease.展开更多
Experimental evidence indicates that chronic mechanical sub-occlusion of the intestine may damage the enteric nervous system （ENS）, although data in humans are lacking. We here describe the first case of enteric deg...Experimental evidence indicates that chronic mechanical sub-occlusion of the intestine may damage the enteric nervous system （ENS）, although data in humans are lacking. We here describe the first case of enteric degenerative neuropathy related to a congenital obstruction of the gut. A 3-year and 9-mo old girl began to complain of vomiting, abdominal distension, constipation with air-fluid levels at plane abdominal radiology. Her subsequent medical history was characterized by 3 operations： the first showed dilated duodeno-jejunal loops in the absence of occlusive lesions; the second （2 years later） was performed to obtain full-thickness biopsies of the dilated intestinal loops and revealed hyperganglionosis at histopathology; the third （9 years after the hyperganglionosis was identified） disclosed a Ladd＇s band which was removed and the associated gut malrotation was corrected. Repeated intraoperative full-thickness biopsies showed enteric degenerative neuropathy along with reduced interstitial cells of Cajal network in dilated loops above the obstruction and a normal neuromuscular layer below the Ladd＇s band. One year after the latest surgery the patient tolerated oral feeding and did well, suggesting that congenital （partial） mechanical obstruction of the small bowel in humans can evoke progressive adaptive changes of the ENS which are similar to those found in animal models of intestinal mechanical occlusion. Such ENS changes mimic neuronal abnormalities observed in intestinal pseudoobstruction.展开更多
Objective: Information regarding the development of the enteric nervous system(ENS) is important for understanding the functional abnormalities of the gut.Because fertilized chicken eggs provide easy access to embryos...Objective: Information regarding the development of the enteric nervous system(ENS) is important for understanding the functional abnormalities of the gut.Because fertilized chicken eggs provide easy access to embryos,chicken models have been widely used to study embryonic development of myenteric plexus;however,no study has been focused on the postnatal period.The aim of this study was to perform a qualitative and quantitative analysis of the nitrergic neurons in the myenteric plexus of developing chickens in the postnatal period.Methods: Whole-mount preparations of the myenteric plexus were made in 7-d,15-d,and 40-d old(adult) chickens of either sex(n=15).The myenteric plexus was studied after nicotinamide adenine dinucleotide phosphate diaphorase(NADPH-d) histochemistry using light microscopy,digital photography,and Image-Pro Plus 6.0 software.The numbers of positively stained neurons and ganglia were counted in the duodenum,jejunum,ileum,caecum,and colon in the different age groups.Data were expressed as mean±standard deviation(SD),and statistical analysis was performed using a one-way analysis of variance(ANOVA) test.Results: The positively stained neurons showed various morphologies and staining intensities,and formed bead-shaped and U-shaped arrangements in the myenteric plexus.The densities of neurons and ganglia increased with age.However,the number of positive neurons per ganglion increased.The number of NADPH-d-positive neurons was highest in the colon,followed by the ileum,the jejunum,the duodenum,and the caeca in all age groups.Conclusions: Developmental changes in the myenteric plexus of chickens continue in the postnatal period,indicating that the maturation process of the gastrointestinal function is gradual.In addition,no significant difference is happening among different intestinal segments during postnatal development,suggesting that the function of different intestinal segments had been determined after birth.展开更多
AIM: To evaluate the effects of protein deprivation on the myenteric plexus of the esophagus of weanling rats. METHODS: Pregnant female Wistar rats were divided into 2 groups: nourished (N),receiving normal diet,and u...AIM: To evaluate the effects of protein deprivation on the myenteric plexus of the esophagus of weanling rats. METHODS: Pregnant female Wistar rats were divided into 2 groups: nourished (N),receiving normal diet,and undernourished (D),receiving a protein-deprived diet,which continued after birth. At twenty-one days of age,13 esophagi from each group were submitted to light microscopy and morphometrical analysis employing the NADH diaphorase,NADPH diaphorase and acetylcholinesterase techniques. Three other esophagi from each group were evaluated with transmission electron microscopy (TEM). RESULTS: In both the NADH- and the NADPH-reactive mounts,the neurons of the N mounts were more intensely stained,while in the D esophagi only the larger neurons were reactive. Many myenteric neurons of N were intensely reactive for AChE activity but only a few neurons of D exhibited these aspects. Ultrastructural analysis revealed that the granular reticulum of N showed large numbers of ribosomes aligned on the outer surface of its regularly arranged membrane while the ribosomes of D were disposed in clusters. The chromatin was more homogeneously scattered inside the neuron nucleus of N as well as the granular component of the nucleolus was evidently more developed in this group. Statistically significant differences between N and D groups were detected in the total estimated number of neurons stained by the NADPH technique. CONCLUSION: The morphological and quantitative data shows that feeding with protein-deprived diet in 21-d old rats induces a delay in the development of the myenteric neurons of the esophagus.展开更多
In our previous study,we showed that with increasing time in culture,the growth characteristics of enteric neural crest-derived cells(ENCCs)change,and that the proliferation,migration and neural differentiation potent...In our previous study,we showed that with increasing time in culture,the growth characteristics of enteric neural crest-derived cells(ENCCs)change,and that the proliferation,migration and neural differentiation potential of these cells in vitro notably diminish.However,there are no studies on the developmental differences in these characteristics between fetal and early-postnatal stages in vitro or in vivo.In this study,we isolated fetal(embryonic day 14.5)and postnatal(postnatal day 2)ENCCs from the intestines of rats.Fetal ENCCs had greater maximum cross-sectional area of the neurospheres,stronger migration ability,and reduced apoptosis,compared with postnatal ENCCs.However,fetal and postnatal ENCCs had a similar differentiation ability.Fetal and postnatal ENCCs both survived after transplant into a rat model of Hirschsprung’s disease.In these rats with Hirschsprung’s disease,the number of ganglionic cells in the myenteric plexus was higher and the distal intestinal pressure change was greater in animals treated with fetal ENCCs compared with those treated with postnatal ENCCs.These findings suggest that,compared with postnatal ENCCs,fetal ENCCs exhibit higher survival and proliferation and migration abilities,and are therefore a more appropriate seed cell for the treatment of Hirschsprung’s disease.This study was approved by the Animal Ethics Committee of the Second Affiliated Hospital of Xi’an Jiaotong University(approval No.2016086)on March 3,2016.展开更多
AIM:To evaluate effects of preand postnatal protein deprivation and postnatal recovery on the myenteric plexus of the rat esophagus. METHODS: Three groups of young Wistar rats (aged 42 d) were studied: normalfed (N42)...AIM:To evaluate effects of preand postnatal protein deprivation and postnatal recovery on the myenteric plexus of the rat esophagus. METHODS: Three groups of young Wistar rats (aged 42 d) were studied: normalfed (N42), proteindeprived (D42), and proteinrecovered (R42). The myenteric neurons of their esophagi were evaluated by histochemical reactions for nicotinamide adenine dinucleotide (NADH), nitrergic neurons (NADPH)diaphorase and acetylcholinesterase (AChE), immunohistochemical reaction for vasoactive intestinal polypeptide (VIP), and ultrastructural analysis by transmission electron microscopy.RESULTS: The cytoplasms of large and medium neurons from the N42 and R42 groups were intensely reactive for NADH. Only a few large neurons from the D42 group exhibited this aspect. NADPH detected in the D42 group exhibited low reactivity. The AChE reactivity was diffuse in neurons from the D42 and R42 groups. The density of large and small varicosities detected by immunohistochemical staining of VIP was low in ganglia from the D42 group. In many neurons from the D42 group, the double membrane of the nuclear envelope and the perinuclear cisterna were not detectable. NADH and NADPH histochemistry revealed no group differences in the prof ile of nerve cell perikarya (ranging from 200 to 400 μm2).CONCLUSION: Protein deprivation causes a delay in neuronal maturation but postnatal recovery can almost completely restore the normal morphology of myenteric neurons.展开更多
Objective:To explore the relationship between climate variables and enteric fever in the city of Ahmedabad and report preliminary findings regarding the influence of El Nino Southern Oscillations and Indian Ocean Dipo...Objective:To explore the relationship between climate variables and enteric fever in the city of Ahmedabad and report preliminary findings regarding the influence of El Nino Southern Oscillations and Indian Ocean Dipole over enteric fever incidence.Method:A total of 29808 Widal positive enteric fever cases reported by the Ahmedabad Municipal Corporation and local climate data in 1985-2017 from Ahmedabad Meteorology Department were analysed.El Nino,La Nina,neutral and Indian Ocean Dipole years as reported by the National Oceanic and Atmospheric Administration for the same period were compared for the incidence of enteric fever.Results:Population-normalized average monthly enteric fever case rates were the highest for El Nino years(25.5),lower for La Nina years(20.5)and lowest for neutral years(17.6).A repeated measures ANOVA analysis showed no significant difference in case rates during the three yearly El Nino Southern Oscillations categories.However,visual profile plot of estimated marginal monthly means showed two distinct characteristics:an early rise and peaking of cases in the El Nino and La Nina years,and a much more restrained rise without conspicuous peaks in neutral years.Further analysis based on monthly El Nino Southern Oscillations categories was conducted to detect differences in median monthly case rates.Median case rates in strong and moderate El Nino months and strong La Nina months were significantly dissimilar from that during neutral months(P<0.001).Conclusions:El Nino Southern Oscillations events influence the incidence of enteric fever cases in Ahmedabad,and further investigation from more cities and towns is required.展开更多
Chronic alcohol abuse damages nearly every organ in the body. The harmful effects of ethanol on thebrain, the liver and the pancreas are well documented. Although chronic alcohol consumption causes serious impairments...Chronic alcohol abuse damages nearly every organ in the body. The harmful effects of ethanol on thebrain, the liver and the pancreas are well documented. Although chronic alcohol consumption causes serious impairments also in the gastrointestinal tract like altered motility, mucosal damage, impaired absorption of nu-trients and inflammation, the effects of chronically consumed ethanol on the enteric nervous system are less detailed. While the nitrergic myenteric neurons play an essential role in the regulation of gastrointestinal peristalsis, it was hypothesised, that these neurons are the first targets of consumed ethanol or its metabolites generated in the different gastrointestinal segments. To reinforce this hypothesis the effects of ethanol on the gastrointestinal tract was investigated in different rodent models with quantitative immunohistochemistry, in vivo and in vitro motility measurements, western blot analysis, evaluation of nitric oxide synthase enzyme activity and bio-imaging of nitric oxide synthesis. These results suggest that chronic alcohol consumption did not result significant neural loss, but primarily impaired the nitrergic pathways in gut region-dependent way leading to disturbed gastrointestinal motility. The gut segment-specific differences in the effects of chronic alcohol consumption highlight the significance the ethanol-induced neuronal microenvironment involving oxidative stress and intestinal microbiota.展开更多
BACKGROUND Cytokines are essential in autoimmune inflammatory processes that accompany type 1 diabetes.Tumor necrosis factor alpha plays a key role among others in modulating enteric neuroinflammation,however,it has a...BACKGROUND Cytokines are essential in autoimmune inflammatory processes that accompany type 1 diabetes.Tumor necrosis factor alpha plays a key role among others in modulating enteric neuroinflammation,however,it has a dual role in cell degeneration or survival depending on different TNFRs.In general,TNFR1 is believed to trigger apoptosis,while TNFR2 promotes cell regeneration.The importance of the neuronal microenvironment has been recently highlighted in gut region-specific diabetic enteric neuropathy,however,the expression and alterations of different TNFRs in the gastrointestinal tract has not been reported.AIM To investigate the TNFR1 and TNFR2 expression in myenteric ganglia and their environment in different intestinal segments of diabetic rats.METHODS Ten weeks after the onset of hyperglycemia,gut segments were taken from the duodenum,ileum and colon of streptozotocin-induced(60 mg/body weight kg i.p.)diabetic(n=17),insulin-treated diabetic(n=15)and sex-and age-matched control(n=15)rats.Myenteric plexus whole-mount preparations were prepared from different gut regions for TNFR1/HuCD or TNFR2/HuCD double-labeling fluorescent immunohistochemistry.TNFR1 and TNFR2 expression was evaluated by post-embedding immunogold electron microscopy on ultrathin sections of myenteric ganglia.TNFRs levels were measured by enzyme-linked immunosorbent assay in muscle/myenteric plexus-containing(MUSCLE-MP)tissue homogenates from different gut segments and experimental conditions.RESULTS A distinct region-dependent TNFRs expression was detected in controls.The density of TNFR1-labeling gold particles was lowest,while TNFR2 density was highest in duodenal ganglia and a decreased TNFRs expression from proximal to distal segments was observed in MUSCLE-MP homogenates.In diabetics,the TNFR2 density was only significantly altered in the duodenum with decrease in the ganglia(0.32±0.02 vs 0.45±0.04,P<0.05),while no significant changes in TNFR1 density was observed.In diabetic MUSCLE-MP homogenates,both TNFRs levels significantly decreased in the duodenum(TNFR1:4.06±0.65 vs 20.32±3.1,P<0.001;TNFR2:11.72±0.39 vs 15.91±1.04,P<0.01),which markedly influenced the TNFR2/TNFR1 proportion in both the ganglia and their muscular environment.Insulin treatment had controversial effects on TNFR expression.CONCLUSION Our findings show diabetes-related region-dependent changes in TNFR expression and suggest that TNFR2 is more affected than TNFR1 in myenteric ganglia in the duodenum of type 1 diabetic rats.展开更多
BACKGROUND Cholecystoenteric fistula(CEF)involves the formation of a spontaneous ano-malous tract between the gallbladder and the adjacent gastrointestinal tract.Chronic gallbladder inflammation can lead to tissue nec...BACKGROUND Cholecystoenteric fistula(CEF)involves the formation of a spontaneous ano-malous tract between the gallbladder and the adjacent gastrointestinal tract.Chronic gallbladder inflammation can lead to tissue necrosis,perforation,and fistulogenesis.The most prevalent cause of CEF is chronic cholelithiasis,which rarely results from malignancy.Because the symptoms and laboratory findings associated with CEF are nonspecific,the condition is often misdiagnosed,pre-senting a challenge to the surgeon when detected intraoperatively.Therefore,a preoperative diagnosis of CEF is crucial.We present the case of a 57-year-old male with advanced gallbladder cancer(GBC)who arrived at the emergency room with persistent vomiting,abdominal pain,and diarrhea.An abdominopelvic computed tomography scan revealed a contracted gallbladder with bubbles in the fundus connected to the second por-tion of the duodenum and transverse colon.We suspected that GBC had invaded the adjacent gastrointestinal tract through a cholecystoduodenal fistula(CDF)or a cholecystocolonic fistula(CCF).He underwent multiple examinations,including esophagogastroduodenoscopy,an upper gastrointestinal series,colo-noscopy,and magnetic resonance cholangiopancreatography;the results of these tests con-firmed a diagnosis of synchronous CDF and CCF.The patient underwent a Roux-en-Y gastrojejunostomy and loop ileostomy to address the severe adhesions that were previously observed to cover the second portion of the duodenum and hepatic flexure of the colon.His symptoms improved with supportive treatment while hospitalized.He initiated oral targeted therapy with lenvatinib for further anticancer treatment.CONCLUSION The combination of imaging and surgery can enhance preoperative diagnosis and alleviate symptoms in patients with GBC complicated by CEF.展开更多
Slow transit constipation has been traditionally considered and classified as a functional disorder. However, clinical and manometric evidence has been accumulating that suggests how most of the motility alterations i...Slow transit constipation has been traditionally considered and classified as a functional disorder. However, clinical and manometric evidence has been accumulating that suggests how most of the motility alterations in STC might be considered of neuropathic type.In addition, further investigations showed that subtle alterations of the enteric nervous system, not evident to conventional histological examination, may be present in these patients. In the present article we will discuss these evidences, and will try to put them in relation with the abnormal motor function of the large bowel documented in this pathological condition.展开更多
Ulcerative colitis(UC) is a leading form of inflammatory bowel disease that involves chronic relapsing or progressive inflammation. As a significant proportion of UC patients treated with conventional therapies do not...Ulcerative colitis(UC) is a leading form of inflammatory bowel disease that involves chronic relapsing or progressive inflammation. As a significant proportion of UC patients treated with conventional therapies do not achieve remission, there is a pressing need for the development of more effective therapies. The human gut contains a large, diverse, and dynamic population of microorganisms, collectively referred to as the enteric microbiota. There is a symbiotic relationship between the human host and the enteric microbiota, which provides nutrition, protection against pathogenic organisms, and promotes immune homeostasis. An imbalance of the normal enteric microbiota composition(termed dysbiosis) underlies the pathogenesis of UC. A reduction of enteric microbiota diversity has been observed in UC patients, mainly affecting the butyrateproducing bacteria, such as Faecalibacterium prausnitzii, which can repress pro-inflammatory cytokines. Many studies have shown that enteric microbiota plays an important role in anti-inflammatory and immunoregulatory activities, which can benefit UC patients. Therefore, manipulation of the dysbiosis is an attractiveapproach for UC therapy.Various therapies targeting a restoration of the enteric microbiota have shown efficacy in treating patients with active and chronic forms of UC.Such therapies include fecal microbiota transplantation,probiotics,prebiotics,antibiotics,helminth therapy,and dietary polyphenols,all of which can alter the abundance and composition of the enteric microbiota.Although there have been many large,randomized controlled clinical trials assessing these treatments,the effectiveness and safety of these bacteria-driven therapies need further evaluation.This review focuses on the important role that the enteric microbiota plays in maintaining intestinal homeostasis and discusses new therapeutic strategies targeting the enteric microbiota for UC.展开更多
基金supported by the National Key R&D Program of China,No.2021YFC2501200(to PC).
文摘Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’s disease.In this review,we summarize the changes in short-chain fatty acid levels and the abundance of short-chain fatty acid-producing bacteria in various samples from patients with Parkinson’s disease,highlighting the critical role of gut homeostasis imbalance in the pathogenesis and progression of the disease.Focusing on the nervous system,we discuss the molecular mechanisms by which short-chain fatty acids influence the homeostasis of both the enteric nervous system and the central nervous system.We identify key processes,including the activation of G protein-coupled receptors and the inhibition of histone deacetylases by short-chain fatty acids.Importantly,structural or functional disruptions in the enteric nervous system mediated by these fatty acids may lead to abnormalα-synuclein expression and gastrointestinal dysmotility,which could serve as an initiating event in Parkinson’s disease.Furthermore,we propose that short-chain fatty acids help establish communication between the enteric nervous system and the central nervous system via the vagal nerve,immune circulation,and endocrine signaling.This communication may shed light on their potential role in the transmission ofα-synuclein from the gut to the brain.Finally,we elucidate novel treatment strategies for Parkinson’s disease that target short-chain fatty acids and examine the challenges associated with translating short-chain fatty acid-based therapies into clinical practice.In conclusion,this review emphasizes the pivotal role of short-chain fatty acids in regulating gut-brain axis integrity and their significance in the pathogenesis of Parkinson’s disease from the perspective of the nervous system.Moreover,it highlights the potential value of short-chain fatty acids in early intervention for Parkinson’s disease.Future research into the molecular mechanisms of short-chain fatty acids and their synergistic interactions with other gut metabolites is likely to advance the clinical translation of innovative short-chain fatty acid-based therapies for Parkinson’s disease.
基金supported by the National Natural Science Foundation of China(No.81700471 and No.82270583)the National Key Research and Development Program of China(No.2022YFC2504005)。
文摘Objective:Diabetes-induced gastrointestinal(GI)motility disorders are increasingly prevalent.Damage to the enteric nervous system(ENS),composed primarily of enteric neurons and glial cells,is an essential mechanism involved in these disorders.Although electroacupuncture(EA)has shown the potential to mitigate enteric neuronal loss,its mechanism is not fully understood.Additionally,the effects of EA on enteric glial cells have not been investigated.Enteric neural precursor cells(ENPCs)contribute to the structural and functional integrity of the ENS,yet whether EA enhances their differentiation into enteric neurons and glial cells remains unexplored.This study investigates whether EA promotes ENS repair through enhancing ENPC-derived neurogenesis and gliogenesis and elucidates the potential molecular mechanisms involved.Methods:Transgenic mice were used to trace Nestin+/nerve growth factor receptor(Ngfr)+ENPCs labeled with green fluorescent protein(GFP)in vivo.Mice were randomly divided into four groups:control,diabetes mellitus(DM),DM+sham EA,and DM+EA.The effects of EA on diabetic mice were evaluated by GI motility,ENS structure,and ENPC differentiation.Glial cell line-derived neurotrophic factor(GDNF)/Ret signaling was detected to clarify the underlying molecular mechanisms.Results:EA alleviated diabetes-induced GI motility disorders,as indicated by reduced whole gut transit time,shortened colonic bead expulsion time,and enhanced smooth muscle contractility.Furthermore,EA attenuated diabetes-induced losses of enteric neurons and glial cells,thereby restoring ENS integrity.Notably,EA reversed the diabetes-induced decrease in ENPCs and significantly increased the absolute number and the proportion of ENPC-derived enteric neurons.However,immunofluorescence analyses revealed no colocalization between EA-induced glial fibrillary acidic protein+glial cells and GFPlabeled ENPCs.Mechanistically,GDNF/Ret signaling was elevated in intestinal tissues and upregulated in ENPCs in EA-treated diabetic mice.Conclusion:EA facilitates ENS repair by promoting Nestin+/Ngfr+ENPC differentiation into enteric neurons via upregulation of GDNF/Ret signaling,and driving enteric gliogenesis from non-Nestin+/Ngfr+ENPCs.These findings highlight EA's role in ameliorating diabetes-induced GI dysmotility through ENPC-derived ENS restoration.
文摘Rationale:Enteric fever is a major public health problem in developing and underdeveloped counties.Extraintestinal manifestations in typhoid are estimated in 27%cases and are associated with severe and complicated diseases.Patients concerns:We report three cases of enteric fever with rare extra intestinal manifestations.Diagnoses:Enteric fever with acute motor-sensory axonal neuropathy,enteric fever with myocarditis,and enteric fever with splenic vein thrombosis.Interventions:All patients were treated with antibiotics.Additionally,Patient 1 was treated with桇immunoglobulin;Patient 2 was treated with vasopressors and anti-cardiac remodeling drugs like ramipril and metoprolol;Patient 3 was treated with anticoagulation with low molecular weight heparin.Outcomes:All patients improved clinically and were followed up on outpatient.Lessons:The diagnosis of enteric fever is challenging and there is an urgent need for prompt-targeted management for better outcomes.Especially in endemic zones and in non-endemic zones as a disease of emporiatric significance.
基金Supported by the Fundamental Research Funds for the Central Universities of Central South University,No.2024XQLH027.
文摘BACKGROUND Colonic anastomotic leakage(AL)remains a feared complication of colorectal surgery.Usually,a defunctioning stoma or a proximal colostomy is performed to reduce the AL rate but cannot completely prevent AL.Moreover,defunctioning colostomy is associated with high morbidity.This study assessed the feasibility of completely preventing colonic AL using total enteric flow diversion without a defunctioning stoma in a pig model of colonic AL.AIM To determine the feasibility of preventing colonic AL via total enteric flow diversion in pigs.METHODS A total of 14 pigs underwent surgery to create colon anaesthesia with severe defects for establishing the AL model.The pigs were then randomized into the control group(n=7),which received no further therapy,and a diversion group(n=7),which underwent placement of a modified ileostomy tube to divert the enteric contents from the colon externally.The general condition,serum Creactive protein level,white blood cell count,5-day incidence of colon AL,and development of abdominal abscesses were evaluated.RESULTS A modified ileostomy tube with a balloon was placed and pressurized to 20 kPa at a distance of 10-20 cm proximal to the ileocecal valve,effectively obstructing the intestine without causing injury and efficiently diverting the enteric contents.In the diversion group,no cases of peritonitis or abscess were observed.In contrast,all pigs in the control group developed either abdominal abscesses or peritonitis.CONCLUSION Instead of ileostomy or colostomy,the total enteric flow diversion technique with the placement of a modified ileostomy tube and balloon in the ileum can effectively or completely prevent colon AL.
基金Supported by Children’s Hospital Foundation at VCU,No.1K23HD097282(to Donowitz JR)National Institutes of Health,No.5R01AI043596(to Donowitz JR)+6 种基金Bill and Melinda Gates Foundation,No.OPP1017093VA Merit Award,No.1I01BX005730VA ShEEP Grants,No.1 IS1 BX004777-01National Institutes of Health Grant,No.2R56DK115377-05A1PIDS Summer Research Scholars AwardVCU SOM Dean’s Summer Research Fellowshipand Research Career Scientist Award from the Department of Veterans Affairs,No.IK6BX004477.
文摘BACKGROUND Environmental enteric dysfunction(EED)is a subclinical condition caused by fecal-oral contamination leading to enteric inflammation and dysbiosis.Bile acids serve to facilitate lipid digestion and absorption,regulate metabolic pathways associated with childhood growth and inflammation,and may be affected by EED.AIM To investigate bile acid metabolism in Bangladeshi children with EED and its association with growth impairment.METHODS We conducted a cross-sectional study of 100 Bangladeshi infants(aged 6-9 months)and quantified serum and fecal bile acids using LC-MS/MS.We compared profiles to a control group of 6 American children(6-12 months)and 80 older Bangladeshi children(aged 2 years).RESULTS Bangladeshi infants had higher levels of plasma unconjugated primary(65.23%vs 44.25%,P=0.003)and sulfated primary bile acids(12.98%vs<0.001%,P=0.01),with lower primary conjugated bile acids(0.69%vs 2.74%,P≤0.001)compared to American children.Stool unconjugated primary bile acids were inversely associated with weight-for-age[regression coefficient(β)=-0.01,P=0.01]and height-for-age Z scores(β=-0.01,P=0.03).Conjugated secondary bile acids were inversely associated with small intestine bacterial overgrowth(β=-1096.68,P=0.05).Fecal myeloperoxidase was associated with sulfated secondary bile acids(β=-0.40,P=0.04).Compared to 2-year-old children,the Bangladeshi infant’s serum had higher levels of unconjugated primary bile acids(65.23%vs 9.20%,P≤0.001)and lower levels of primary conjugated bile acids(0.69%vs 80.38%,P≤0.001).CONCLUSION Our data suggests an age-dependent defect in conjugation of primary bile acids in Bangladeshi children with compensatory hydrophilic shunting.Additionally,bile acid profiles are associated with intestinal overgrowth.
基金Supported by Science and Technology Plan Project of Zhongshan City(2022B1126).
文摘[Objectives]To explore the mechanism of action of Tongxieyaofang ultrafine granular powder in treating visceral hypersensitivity in rats with diarrhea-predominant irritable bowel syndrome(IBS-D)based on enteric glial cells(EGCs).[Methods]Eighty-four healthy male Wistar rats of SPF grade were selected and randomly assigned to seven groups,each comprising 12 rats:a normal control group,a model control group,a traditional Tongxieyaofang granular powder group(4.060 g/kg),three Tongxieyaofang ultrafine granular powder groups at low,medium,and high doses(1.015,2.030,and 4.060 g/kg of raw drug,respectively),and a pinaverium bromide group(0.018 g/kg).With the exception of the normal control group,all other groups were subjected to an IBS-D visceral hypersensitivity sensitivity model in rats developed by the chronic water avoidance stress method.Three days post modeling,the rats received continuous oral gavage administration for 8 d.Following the treatment period,serum and colon tissue samples were collected from each group.The BDNF level in the serum was quantified using ELISA.Additionally,the protein expression levels of GFAP,BDNF,and TrkB in colon tissues were assessed via Western blot assay.[Results]Compared to the normal control group,the serum BDNF levels in the model control group were significantly elevated(P<0.01).In contrast,each treatment group exhibited a significant reduction in serum BDNF levels relative to the model control group(P<0.01).Furthermore,the protein expression levels of GFAP,BDNF,and TrkB in colon tissue were significantly higher in the model control group compared to the normal control group(P<0.05,P<0.01).Conversely,these protein expressions were significantly decreased in each treatment group compared to the model control group(P<0.05,P<0.01).[Conclusions]Tongxieyaofang ultrafine granular powder effectively alleviates visceral sensitivity in IBS-D rats and inhibits the activation of EGCs,speculating that its mechanism of action involves the suppression of abnormal EGC activation.
基金Supported by PRONEX CNPq/FUNCAP,No.PR2-0101-00060.01.00/15Sao Paulo Research Foundation(FAPESP),No.2014/25927-2 and No.2018/07862-1.
文摘Clostridioides difficile(C.difficile)is the most common pathogen causing health care-associated infections.C.difficile TcdA and TcdB have been shown to activate enteric neurons;however,what population of these cells is more profoundly influenced and the mechanism underlying these effects remain unknown.AIM To characterize a specific population of TcdA-affected myenteric neurons and investigate the role of the P2X7 receptor in TcdA-induced ileal inflammation,cell death,and the changes in the enteric nervous system in mice.METHODS Swiss mice were used to model TcdA-induced ileitis in ileal loops exposed to TcdA(50μg/Loop)for 4 h.To investigate the role of the P2X7 receptor,Brilliant Blue G(50 mg/kg,i.p.),which is a nonspecific P2X7 receptor antagonist,or A438079(0.7μg/mouse,i.p.),which is a competitive P2X7 receptor antagonist,were injected one hour prior to TcdA challenge.Ileal samples were collected to analyze the expression of the P2X7 receptor(by quantitative real-time polymerase chain reaction and immunohistochemistry),the population of myenteric enteric neurons(immunofluorescence),histological damage,intestinal inflammation,cell death(terminal deoxynucleotidyltransferasemediated dUTP-biotin nick end labeling),neuronal loss,and S100B synthesis(immunohistochemistry).RESULTS TcdA upregulated(P<0.05)the expression of the P2X7 receptor gene in the ileal tissues,increasing the level of this receptor in myenteric neurons compared to that in control mice.Comparison with the control mice indicated that TcdA promoted(P<0.05)the loss of myenteric calretinin+(Calr)and choline acetyltransferase+neurons and increased the number of nitrergic+and Calr+neurons expressing the P2X7 receptor.Blockade of the P2X7 receptor decreased TcdAinduced intestinal damage,cytokine release[interleukin(IL)-1β,IL-6,IL-8,and tumor necrosis factor-α],cell death,enteric neuron loss,and S100B synthesis in the mouse ileum.CONCLUSION Our findings demonstrated that TcdA induced the upregulation of the P2X7 receptor,which promoted enteric neuron loss,S100B synthesis,tissue damage,inflammation,and cell death in the mouse ileum.These findings contribute to the future directions in understanding the mechanism involved in intestinal dysfunction reported in patients after C.difficile infection.
基金provided by the National High Technology Research and Development Program("863"Program)of China,grant no.2006AA09Z162the National Key Scientific and Technological Project,grant no.908-01-ZH3
文摘Through investigating ten recreational marine beaches in China, we aimed to detect the occurrence of human enteric viruses in coastal bathing beaches and find a correlationship, if any, between the presence of enteric viruses in surface seawater and the concentrations of fecal coliforms, the conventional indicator of fecal pollution. In this study, twenty seawater samples were assayed for fecal coliforms and human pathogenic enteric viruses （hepatitis A viruses, rotaviruses, polioviruses） analysis. Enteric viruses were detected by RT-PCR, in 20 sample sites, 5%, 40%, 40% were positive for the presence of human hepatitis A viruses, rotaviruses, polioviruses, respectively. Seven of 20 sites are suffering from severe fecal contamination, based on traditional plate counts of fecal coliform outnumbering the established thresholds for recreation. Additionally, statistical analysis presented that no correlation was found between bacterial indicators and viruses in surface seawaters. The data confirmed that indicator bacteria in water are not reflective of the presence of enteric viruses in marine waters. Thus, current recreational water quality standards of both bacterial and viral indices should be reevaluated.
文摘Diabetes,commonly known for its metabolic effects,also critically affects the enteric nervous system(ENS),which is essential in regulating gastrointestinal(GI)motility,secretion,and absorption.The development of diabetes-induced enteric neuropathy can lead to various GI dysfunctions,such as gastroparesis and irregular bowel habits,primarily due to disruptions in the function of neuronal and glial cells within the ENS,as well as oxidative stress and inflammation.This editorial explores the pathophysiological mechanisms underlying the development of enteric neuropathy in diabetic patients.Additionally,it discusses the latest advances in diagnostic approaches,emphasizing the need for early detection and intervention to mitigate GI complications in diabetic individuals.The editorial also reviews current and emerging therapeutic strategies,focusing on pharmacological treatments,dietary management,and potential neuromodulatory interventions.Ultimately,this editorial highlights the necessity of a multidisciplinary approach in managing enteric neuropathy in diabetes,aiming to enhance patient quality of life and address a frequently overlooked complication of this widespread disease.
基金Supported by the Italian Ministry of Education, University and Research (CCOFIN Project No. 2004062155 to RDeG,2004055120 to GB and 2003064378 to RDeG, GB and VS)
文摘Experimental evidence indicates that chronic mechanical sub-occlusion of the intestine may damage the enteric nervous system （ENS）, although data in humans are lacking. We here describe the first case of enteric degenerative neuropathy related to a congenital obstruction of the gut. A 3-year and 9-mo old girl began to complain of vomiting, abdominal distension, constipation with air-fluid levels at plane abdominal radiology. Her subsequent medical history was characterized by 3 operations： the first showed dilated duodeno-jejunal loops in the absence of occlusive lesions; the second （2 years later） was performed to obtain full-thickness biopsies of the dilated intestinal loops and revealed hyperganglionosis at histopathology; the third （9 years after the hyperganglionosis was identified） disclosed a Ladd＇s band which was removed and the associated gut malrotation was corrected. Repeated intraoperative full-thickness biopsies showed enteric degenerative neuropathy along with reduced interstitial cells of Cajal network in dilated loops above the obstruction and a normal neuromuscular layer below the Ladd＇s band. One year after the latest surgery the patient tolerated oral feeding and did well, suggesting that congenital （partial） mechanical obstruction of the small bowel in humans can evoke progressive adaptive changes of the ENS which are similar to those found in animal models of intestinal mechanical occlusion. Such ENS changes mimic neuronal abnormalities observed in intestinal pseudoobstruction.
基金Project supported by the National Natural Science Foundation of China(Nos.31172282 and 31272521)the Priority Academic Program Development of Jiangsu Higher Education Institutionsthe Natural Science Foundation of Jiangsu Province for Youths(No.BK20130681),China
文摘Objective: Information regarding the development of the enteric nervous system(ENS) is important for understanding the functional abnormalities of the gut.Because fertilized chicken eggs provide easy access to embryos,chicken models have been widely used to study embryonic development of myenteric plexus;however,no study has been focused on the postnatal period.The aim of this study was to perform a qualitative and quantitative analysis of the nitrergic neurons in the myenteric plexus of developing chickens in the postnatal period.Methods: Whole-mount preparations of the myenteric plexus were made in 7-d,15-d,and 40-d old(adult) chickens of either sex(n=15).The myenteric plexus was studied after nicotinamide adenine dinucleotide phosphate diaphorase(NADPH-d) histochemistry using light microscopy,digital photography,and Image-Pro Plus 6.0 software.The numbers of positively stained neurons and ganglia were counted in the duodenum,jejunum,ileum,caecum,and colon in the different age groups.Data were expressed as mean±standard deviation(SD),and statistical analysis was performed using a one-way analysis of variance(ANOVA) test.Results: The positively stained neurons showed various morphologies and staining intensities,and formed bead-shaped and U-shaped arrangements in the myenteric plexus.The densities of neurons and ganglia increased with age.However,the number of positive neurons per ganglion increased.The number of NADPH-d-positive neurons was highest in the colon,followed by the ileum,the jejunum,the duodenum,and the caeca in all age groups.Conclusions: Developmental changes in the myenteric plexus of chickens continue in the postnatal period,indicating that the maturation process of the gastrointestinal function is gradual.In addition,no significant difference is happening among different intestinal segments during postnatal development,suggesting that the function of different intestinal segments had been determined after birth.
文摘AIM: To evaluate the effects of protein deprivation on the myenteric plexus of the esophagus of weanling rats. METHODS: Pregnant female Wistar rats were divided into 2 groups: nourished (N),receiving normal diet,and undernourished (D),receiving a protein-deprived diet,which continued after birth. At twenty-one days of age,13 esophagi from each group were submitted to light microscopy and morphometrical analysis employing the NADH diaphorase,NADPH diaphorase and acetylcholinesterase techniques. Three other esophagi from each group were evaluated with transmission electron microscopy (TEM). RESULTS: In both the NADH- and the NADPH-reactive mounts,the neurons of the N mounts were more intensely stained,while in the D esophagi only the larger neurons were reactive. Many myenteric neurons of N were intensely reactive for AChE activity but only a few neurons of D exhibited these aspects. Ultrastructural analysis revealed that the granular reticulum of N showed large numbers of ribosomes aligned on the outer surface of its regularly arranged membrane while the ribosomes of D were disposed in clusters. The chromatin was more homogeneously scattered inside the neuron nucleus of N as well as the granular component of the nucleolus was evidently more developed in this group. Statistically significant differences between N and D groups were detected in the total estimated number of neurons stained by the NADPH technique. CONCLUSION: The morphological and quantitative data shows that feeding with protein-deprived diet in 21-d old rats induces a delay in the development of the myenteric neurons of the esophagus.
基金supported by the National Natural Science Foundation of China,Nos.82071692(to HY),81741096(to HY),81770513(to YG),81270435(to WKP)Shaanxi Youth Science and Technology Project of China,No.2019KJXX-044(to HY)+1 种基金the National Natural Science Foundation of Shaanxi Province of China,No.2020JM-407(to HY)Fund Project of the Second Affiliated Hospital,Xi’an Jiaotong University No.RC(XM)201703(to HY).
文摘In our previous study,we showed that with increasing time in culture,the growth characteristics of enteric neural crest-derived cells(ENCCs)change,and that the proliferation,migration and neural differentiation potential of these cells in vitro notably diminish.However,there are no studies on the developmental differences in these characteristics between fetal and early-postnatal stages in vitro or in vivo.In this study,we isolated fetal(embryonic day 14.5)and postnatal(postnatal day 2)ENCCs from the intestines of rats.Fetal ENCCs had greater maximum cross-sectional area of the neurospheres,stronger migration ability,and reduced apoptosis,compared with postnatal ENCCs.However,fetal and postnatal ENCCs had a similar differentiation ability.Fetal and postnatal ENCCs both survived after transplant into a rat model of Hirschsprung’s disease.In these rats with Hirschsprung’s disease,the number of ganglionic cells in the myenteric plexus was higher and the distal intestinal pressure change was greater in animals treated with fetal ENCCs compared with those treated with postnatal ENCCs.These findings suggest that,compared with postnatal ENCCs,fetal ENCCs exhibit higher survival and proliferation and migration abilities,and are therefore a more appropriate seed cell for the treatment of Hirschsprung’s disease.This study was approved by the Animal Ethics Committee of the Second Affiliated Hospital of Xi’an Jiaotong University(approval No.2016086)on March 3,2016.
基金Supported by Conselho Nacional de Desenvolvimento Cientifico e Tecnologico - CNPq and FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo) grant, No. 04/00746-3
文摘AIM:To evaluate effects of preand postnatal protein deprivation and postnatal recovery on the myenteric plexus of the rat esophagus. METHODS: Three groups of young Wistar rats (aged 42 d) were studied: normalfed (N42), proteindeprived (D42), and proteinrecovered (R42). The myenteric neurons of their esophagi were evaluated by histochemical reactions for nicotinamide adenine dinucleotide (NADH), nitrergic neurons (NADPH)diaphorase and acetylcholinesterase (AChE), immunohistochemical reaction for vasoactive intestinal polypeptide (VIP), and ultrastructural analysis by transmission electron microscopy.RESULTS: The cytoplasms of large and medium neurons from the N42 and R42 groups were intensely reactive for NADH. Only a few large neurons from the D42 group exhibited this aspect. NADPH detected in the D42 group exhibited low reactivity. The AChE reactivity was diffuse in neurons from the D42 and R42 groups. The density of large and small varicosities detected by immunohistochemical staining of VIP was low in ganglia from the D42 group. In many neurons from the D42 group, the double membrane of the nuclear envelope and the perinuclear cisterna were not detectable. NADH and NADPH histochemistry revealed no group differences in the prof ile of nerve cell perikarya (ranging from 200 to 400 μm2).CONCLUSION: Protein deprivation causes a delay in neuronal maturation but postnatal recovery can almost completely restore the normal morphology of myenteric neurons.
基金funded by Public Health Research Initiative(PHRI)Research grant awarded by PHFI with the financial support of Department of Science and Technology(No.PHRI LN0019).
文摘Objective:To explore the relationship between climate variables and enteric fever in the city of Ahmedabad and report preliminary findings regarding the influence of El Nino Southern Oscillations and Indian Ocean Dipole over enteric fever incidence.Method:A total of 29808 Widal positive enteric fever cases reported by the Ahmedabad Municipal Corporation and local climate data in 1985-2017 from Ahmedabad Meteorology Department were analysed.El Nino,La Nina,neutral and Indian Ocean Dipole years as reported by the National Oceanic and Atmospheric Administration for the same period were compared for the incidence of enteric fever.Results:Population-normalized average monthly enteric fever case rates were the highest for El Nino years(25.5),lower for La Nina years(20.5)and lowest for neutral years(17.6).A repeated measures ANOVA analysis showed no significant difference in case rates during the three yearly El Nino Southern Oscillations categories.However,visual profile plot of estimated marginal monthly means showed two distinct characteristics:an early rise and peaking of cases in the El Nino and La Nina years,and a much more restrained rise without conspicuous peaks in neutral years.Further analysis based on monthly El Nino Southern Oscillations categories was conducted to detect differences in median monthly case rates.Median case rates in strong and moderate El Nino months and strong La Nina months were significantly dissimilar from that during neutral months(P<0.001).Conclusions:El Nino Southern Oscillations events influence the incidence of enteric fever cases in Ahmedabad,and further investigation from more cities and towns is required.
基金Supported by The János Bolyai Research Scholarship of the Hungarian Academy of Sciences(Mária Bagyánszki)by the Hungarian Scientific Research Fund,OTKA grant PD 108309(Nikolett Bódi)
文摘Chronic alcohol abuse damages nearly every organ in the body. The harmful effects of ethanol on thebrain, the liver and the pancreas are well documented. Although chronic alcohol consumption causes serious impairments also in the gastrointestinal tract like altered motility, mucosal damage, impaired absorption of nu-trients and inflammation, the effects of chronically consumed ethanol on the enteric nervous system are less detailed. While the nitrergic myenteric neurons play an essential role in the regulation of gastrointestinal peristalsis, it was hypothesised, that these neurons are the first targets of consumed ethanol or its metabolites generated in the different gastrointestinal segments. To reinforce this hypothesis the effects of ethanol on the gastrointestinal tract was investigated in different rodent models with quantitative immunohistochemistry, in vivo and in vitro motility measurements, western blot analysis, evaluation of nitric oxide synthase enzyme activity and bio-imaging of nitric oxide synthesis. These results suggest that chronic alcohol consumption did not result significant neural loss, but primarily impaired the nitrergic pathways in gut region-dependent way leading to disturbed gastrointestinal motility. The gut segment-specific differences in the effects of chronic alcohol consumption highlight the significance the ethanol-induced neuronal microenvironment involving oxidative stress and intestinal microbiota.
基金Supported by Hungarian National Research,Development and Innovation Fund Projects,No.GINOP-2.3.3-15-2016-00006Hungarian NKFIH Fund Project,No.FK131789(to Bódi N)+2 种基金János Bolyai Research Scholarship of the Hungarian Academy of Sciences(to Bódi N)ÚNKP-21-5-New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research,Development and Innovation Fund(to Bódi N)Gedeon Richter Plc Centenary Foundation(to Bódi N).
文摘BACKGROUND Cytokines are essential in autoimmune inflammatory processes that accompany type 1 diabetes.Tumor necrosis factor alpha plays a key role among others in modulating enteric neuroinflammation,however,it has a dual role in cell degeneration or survival depending on different TNFRs.In general,TNFR1 is believed to trigger apoptosis,while TNFR2 promotes cell regeneration.The importance of the neuronal microenvironment has been recently highlighted in gut region-specific diabetic enteric neuropathy,however,the expression and alterations of different TNFRs in the gastrointestinal tract has not been reported.AIM To investigate the TNFR1 and TNFR2 expression in myenteric ganglia and their environment in different intestinal segments of diabetic rats.METHODS Ten weeks after the onset of hyperglycemia,gut segments were taken from the duodenum,ileum and colon of streptozotocin-induced(60 mg/body weight kg i.p.)diabetic(n=17),insulin-treated diabetic(n=15)and sex-and age-matched control(n=15)rats.Myenteric plexus whole-mount preparations were prepared from different gut regions for TNFR1/HuCD or TNFR2/HuCD double-labeling fluorescent immunohistochemistry.TNFR1 and TNFR2 expression was evaluated by post-embedding immunogold electron microscopy on ultrathin sections of myenteric ganglia.TNFRs levels were measured by enzyme-linked immunosorbent assay in muscle/myenteric plexus-containing(MUSCLE-MP)tissue homogenates from different gut segments and experimental conditions.RESULTS A distinct region-dependent TNFRs expression was detected in controls.The density of TNFR1-labeling gold particles was lowest,while TNFR2 density was highest in duodenal ganglia and a decreased TNFRs expression from proximal to distal segments was observed in MUSCLE-MP homogenates.In diabetics,the TNFR2 density was only significantly altered in the duodenum with decrease in the ganglia(0.32±0.02 vs 0.45±0.04,P<0.05),while no significant changes in TNFR1 density was observed.In diabetic MUSCLE-MP homogenates,both TNFRs levels significantly decreased in the duodenum(TNFR1:4.06±0.65 vs 20.32±3.1,P<0.001;TNFR2:11.72±0.39 vs 15.91±1.04,P<0.01),which markedly influenced the TNFR2/TNFR1 proportion in both the ganglia and their muscular environment.Insulin treatment had controversial effects on TNFR expression.CONCLUSION Our findings show diabetes-related region-dependent changes in TNFR expression and suggest that TNFR2 is more affected than TNFR1 in myenteric ganglia in the duodenum of type 1 diabetic rats.
文摘BACKGROUND Cholecystoenteric fistula(CEF)involves the formation of a spontaneous ano-malous tract between the gallbladder and the adjacent gastrointestinal tract.Chronic gallbladder inflammation can lead to tissue necrosis,perforation,and fistulogenesis.The most prevalent cause of CEF is chronic cholelithiasis,which rarely results from malignancy.Because the symptoms and laboratory findings associated with CEF are nonspecific,the condition is often misdiagnosed,pre-senting a challenge to the surgeon when detected intraoperatively.Therefore,a preoperative diagnosis of CEF is crucial.We present the case of a 57-year-old male with advanced gallbladder cancer(GBC)who arrived at the emergency room with persistent vomiting,abdominal pain,and diarrhea.An abdominopelvic computed tomography scan revealed a contracted gallbladder with bubbles in the fundus connected to the second por-tion of the duodenum and transverse colon.We suspected that GBC had invaded the adjacent gastrointestinal tract through a cholecystoduodenal fistula(CDF)or a cholecystocolonic fistula(CCF).He underwent multiple examinations,including esophagogastroduodenoscopy,an upper gastrointestinal series,colo-noscopy,and magnetic resonance cholangiopancreatography;the results of these tests con-firmed a diagnosis of synchronous CDF and CCF.The patient underwent a Roux-en-Y gastrojejunostomy and loop ileostomy to address the severe adhesions that were previously observed to cover the second portion of the duodenum and hepatic flexure of the colon.His symptoms improved with supportive treatment while hospitalized.He initiated oral targeted therapy with lenvatinib for further anticancer treatment.CONCLUSION The combination of imaging and surgery can enhance preoperative diagnosis and alleviate symptoms in patients with GBC complicated by CEF.
文摘Slow transit constipation has been traditionally considered and classified as a functional disorder. However, clinical and manometric evidence has been accumulating that suggests how most of the motility alterations in STC might be considered of neuropathic type.In addition, further investigations showed that subtle alterations of the enteric nervous system, not evident to conventional histological examination, may be present in these patients. In the present article we will discuss these evidences, and will try to put them in relation with the abnormal motor function of the large bowel documented in this pathological condition.
文摘Ulcerative colitis(UC) is a leading form of inflammatory bowel disease that involves chronic relapsing or progressive inflammation. As a significant proportion of UC patients treated with conventional therapies do not achieve remission, there is a pressing need for the development of more effective therapies. The human gut contains a large, diverse, and dynamic population of microorganisms, collectively referred to as the enteric microbiota. There is a symbiotic relationship between the human host and the enteric microbiota, which provides nutrition, protection against pathogenic organisms, and promotes immune homeostasis. An imbalance of the normal enteric microbiota composition(termed dysbiosis) underlies the pathogenesis of UC. A reduction of enteric microbiota diversity has been observed in UC patients, mainly affecting the butyrateproducing bacteria, such as Faecalibacterium prausnitzii, which can repress pro-inflammatory cytokines. Many studies have shown that enteric microbiota plays an important role in anti-inflammatory and immunoregulatory activities, which can benefit UC patients. Therefore, manipulation of the dysbiosis is an attractiveapproach for UC therapy.Various therapies targeting a restoration of the enteric microbiota have shown efficacy in treating patients with active and chronic forms of UC.Such therapies include fecal microbiota transplantation,probiotics,prebiotics,antibiotics,helminth therapy,and dietary polyphenols,all of which can alter the abundance and composition of the enteric microbiota.Although there have been many large,randomized controlled clinical trials assessing these treatments,the effectiveness and safety of these bacteria-driven therapies need further evaluation.This review focuses on the important role that the enteric microbiota plays in maintaining intestinal homeostasis and discusses new therapeutic strategies targeting the enteric microbiota for UC.
