Enteric neuropathy in diabetes:Implications for gastrointestinal function

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.

Porcine enteric alphacoronavirus infection increases lipid droplet accumulation to facilitate the virus replication

Coronaviruses are widely transmissible between humans and animals, causing diseases of varying severity. Porcine enteric alphacoronavirus(PEAV) is a newly-discovered pathogenic porcine enteric coronavirus in recent years, which causes watery diarrhea in newborn piglets. The host inflammatory responses to PEAV and its metabolic regulation mechanisms remain unclear, and no antiviral studies have been reported. Therefore, we investigated the pathogenic mechanism and antiviral drugs of PEAV. The transcriptomic analysis of PEAV-infected host cells revealed that PEAV could upregulate lipid metabolism pathways. In lipid metabolism, steady-state energy processes, which can be mediated by lipid droplets(LDs), are the main functions of organelles. LDs are also important in viral infection and inflammation. In infected cells, PEAV increased LD accumulation, upregulated NF-κB signaling, promoted the production of the inflammatory cytokines IL-1β and IL-8, and induced cell death. Inhibiting LD accumulation with a DGAT-1 inhibitor significantly inhibited PEAV replication, downregulated the NF-κB signaling pathway, reduced the production of IL-1β and IL-8, and inhibited cell death. The NF-κB signaling pathway inhibitor BAY11-7082 significantly inhibited LD accumulation and PEAV replication. Metformin hydrochloride also exerted anti-PEAV effects and significantly inhibited LD accumulation, downregulated the NF-κB signaling pathway, reduced the production of IL-1β and IL-8, and inhibited cell death. LD accumulation in the lipid metabolism pathway therefore plays an important role in the replication and pathogenesis of PEAV, and metformin hydrochloride inhibits LD accumulation and the inflammatory response to exert anti-PEAV activity and reducing pathological injury. These findings contribute new targets for developing treatments for PEAV infections.

Prevalence of Enteric Pathogens Associated with Infections among Table Egg Consumers in Some Primary Health Establishments in the Center Region of Cameroon

Method: In Cameroon limited data are available regarding the prevalence of enteric bacteria associated with table egg consuming infections. As such, a situational-based study was performed in patients with complains of stomach disorders after egg consumption. Data related to sociodemographic characteristics and other factors were collected using a structured based questionnaire. Stool culture of utmost importance in stomach disorders patients and serum were collected for typhoid serological test. Results: A total of 207 participants took part in the survey, Results indicated nontyphoidal Salmonella infections were highest in the 3 areas of study with Mfoundi (73.44%) having the highest level of infection compared to other bacterial infection. other enteric bacteria associated to this infection were E. coli serotype 157, Aeromonas, Citrobacter freundii, Enterobacter cloaca and typhi salmonella. Meanwhile salmonelosis caused by typhic salmonella had highest prevalence in the Lekie Division (13.11%) as a result of poor hygienic practices associated with the conservation and preparation of eggs, Stool culture was observed to detect more positive cases in the diagnosis of typhoid fever than Widal test, but with no statistically significant (p > 0.05) difference between the stool culture and Widal test in the 3 areas of study. Conclusion: this study revealed that egg consumers are pruned to enteric bacterial and salmonella infections depending on how and where egg is consumed.

Phytochemical screening and antibacterial activities of Momordica charantia and Vernonia amygdalina extracts on some selected enteric isolates

Background:This research focuses on herbal medicine,an ancient healthcare practice,exploring the antibacterial attributes of fresh and dried leaf extracts from Momordica charantia(commonly known as Bitter melon)and Vernonia amygdalina(Bitter leaf).The study specifically investigates their effects on different bacterial strains associated with gastroenteritis.Methods:Four enteric bacterial isolates-Klebsiella pneumoniae,Salmonella typhi,Escherichia coli,and Proteus mirabilis-were obtained from the Medical Laboratory Unit at Babcock University Teaching Hospital in Ilishan-Remo,Ogun State.Phytochemical screening and antibacterial testing were conducted using standard biochemical techniques and the Punch-hole agar diffusion method,respectively.Results:Qualitative phytochemical screening of the plant extracts revealed the presence of flavonoids,glycosides,and saponin in both plants,excluding terpenoids.Alkaloids were identified only in Vernonia amygdalina.Despite these phytochemicals,neither plant displayed inhibitory effects on the tested bacterial isolates(Escherichia coli,Proteus mirabilis,Klebsiella pneumoniae,and Salmonella typhi)when tested individually or in combination.Intriguingly,combining the fresh and dried leaf extracts of Momordica charantia and Vernonia amygdalina with a standard drug resulted in smaller mean zone diameters of inhibition(Escherichia coli range:14 mm–16 mm,Proteus mirabilis range:31 mm–35 mm,Klebsiella pneumoniae range:13 mm–22 mm,and Salmonella typhi range:35 mm–38 mm)compared to the drug tested alone(16 mm–45 mm).Conclusion:Despite previous indications of antibacterial properties in various extracts of V.amygdalina and M.charantia leaves,our study presents contradictory results,prompting the need for further investigation despite the presence of significant phytochemicals.

Global burden of enteric infections related foodborne diseases,1990-2021:findings from the Global Burden of Disease Study 2021

Background:Understanding the global burden of enteric infections is crucial for prioritizing control strategies for foodborne and waterborne diseases.This study aimed to assess the global burden of enteric infections in 2021 and identify risk factors from One Health aspects.Methods:Leveraging the Global Burden of Disease(GBD)2021 database,the incidence,disability-adjusted life years(DALYs),and deaths of enteric infections and the subtypes were estimated,including diarrheal diseases,typhoid and paratyphoid fever,invasive non-typhoidal Salmonella(iNTS)infections,and other intestinal infectious diseases.The estimates were quantified by absolute number,age-standardized incidence rate(ASIR),agestandardized mortality rate(ASMR)and age-standardized DALY rate with 95%uncertainty intervals(UIs).Thirteen pathogens and three risk factors associated with diarrheal diseases were analyzed.Results:In 2021,the global age-standardized DALY rate of enteric infections was 1020.15 per 100,000 popultion(95%UI:822.70-1259.39 per 100,000 population)with an estimated annual percentage change(EAPC)of-4.11%(95%confidence interval:-4.31%to-3.90%)in 1990-2021.A larger burden was observed in regions with lower socio-demographic index(SDI)levels.Diarrheal disease was the most serious subtype with Western Sub-Saharan Africa exhibiting the highest age-standardized DALY rate(2769.81 per 100,000 population,95%UI:1976.80-3674.41 per 100,000 population).Children under 5 and adults over 65 years suffered more from diarrheal diseases with the former experiencing the highest global age-standardized DALY rate(9382.46 per 100,000 population,95%UI:6771.76-13,075.12 per 100,000 population).Rotavirus remained the leading cause of diarrheal diseases despite a cross-year decline in the observed age-standardized DALY rate.Unsafe water,sanitation,and handwashing contributed most to the disease burden.Conclusion:The reduced burden of enteric infections suggested the effectiveness of previous control strategies;however,more efforts should be made in vulnerable regions and populations through a One Health approach.

Protocol for detection of pathogenic enteric RNA viruses by regular monitoring of environmental samples from wastewater treatment plants using droplet digital PCR

Background:The present comprehensive protocol is focused on the detection of pathogenic enteric RNA viruses,explicitly focusing on norovirus genogroup II(GII),astrovirus,rotavirus,Aichi virus,sapovirus,hepatitis A and E viruses in wastewater treatment plants through droplet digital PCR(ddPCR).Enteric viruses are of significant public health concern,as they are the leading cause of diseases like gastroenteritis.Regular monitoring of environmental samples,particularly from wastewater treatment plants,is crucial for early detection and control of these viruses.This research aims to improve the understanding of the prevalence and dynamics of enteric viruses in urban India and will serve as a model for similar studies in other regions.Our protocol's objective is to establish a novel ddPCRbased methodology for the detection and molecular characterization of enteric viruses present in wastewater samples sourced from Bhopal,India.Our assay is capable of accurately quantifying virus concentrations without standard curves,minimizing extensive optimization,and enhancing sensitivity and precision,especially for low-abundance targets.Methods:The study involves fortnightly collecting and analyzing samples from nine wastewater treatment plants over two years,ensuring comprehensive coverage and consistent data.Our study innovatively applies ddPCR to simultaneously detect and quantify enteric viruses in wastewater,a more advanced technique.Additionally,we will employ next-generation sequencing for detailed viral genome identification in samples tested positive for pathogenic viruses.Conclusion:This study will aid in understanding these viruses’genetic diversity and mutation rates,which is crucial for developing tailored intervention strategies.The findings will be instrumental in shaping public health responses and improving epidemiological surveillance,especially in localities heaving sewage networks.

Nursing Experience of Early Application of Nasoenteric Tube for Enteral Nutrition in Critically Ill ICU Patients

Objective:To investigate the effective nursing measures of early application of nasoenteric tube for enteral nutrition in critically ill patients in ICU,and to summarize the nursing experience.Methods:The study was carried out in June 2023–November 2023.62 samples of ICU critically ill patients were selected,all of whom used enteral nutrition by mesenteric tube and were grouped into an observation group(n=31)and a control group(n=31)by using the numerical table randomization method.The patients in the control group were basic nursing interventions,and the patients in the observation group were comprehensive quality care,comparing the nutritional indexes,complication rates,and nursing satisfaction between the two groups.Results:All nutritional indicators of the observation group were higher than those of the control group after nursing intervention(P<0.05);the complication rate of the observation group was lower than that of the control group(P<0.05);the nursing satisfaction of the observation group was higher than that of the control group(P<0.05).Conclusion:Comprehensive quality nursing care during the early application of a gastroenteric tube for enteral nutrition in critically ill patients in the ICU can improve nutritional indexes,reduce the incidence of complications and improve nursing satisfaction.

P2X7 receptor blockade decreases inflammation,apoptosis,and enteric neuron loss during Clostridioides difficile toxin A-induced ileitis in mice

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.

Investigation of fecal coliform and typical enteric virus in representative beaches of China

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.

Enteric neuropathology of congenital intestinal obstruction:A case report

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.

Effects of combined pre- and post-natal protein deprivation on the myenteric plexus of the esophagus of weanling rats:A histochemical,quantitative and ultrastructural study

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.

Phenotypic and functional comparison of rat enteric neural crest-derived cells during fetal and earlypostnatal stages

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.

Effects of perinatal protein deprivation and recovery on esophageal myenteric plexus

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.

Effect of El Nino Southern Oscillations on the incidence of enteric fever in Ahmedabad,India from 1985 to 2017

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.

Gut region-dependent alterations of nitrergic myenteric neurons after chronic alcohol consumption

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.

Gut region-specific TNFR expression:TNFR2 is more affected than TNFR1 in duodenal myenteric ganglia of diabetic rats

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.

Cholecystoenteric fistula in a patient with advanced gallbladder cancer: A case report and review of literature

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.

Slow transit constipation: A functional disorder becomes an enteric neuropathy

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.

Enteric microbiota leads to new therapeutic strategies for ulcerative colitis

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.

Diabetes-related alterations in the enteric nervous system and its microenvironment

Gastric intestinal symptoms common among diabetic patients are often caused by intestinal motility abnormalities related to enteric neuropathy. It has recently been demonstrated that the nitrergic subpopulation of myenteric neurons are especially susceptible to the development of diabetic neuropathy. Additionally, different susceptibility of nitrergic neurons located in different intestinal segments to diabetic damage and their different levels of responsiveness to insulin treatment have been revealed. These findings indicate the importance of the neuronal microenvironment in the pathogenesis of diabetic nitrergic neuropathy. The main focus of this review therefore was to summarize recent advances related to the diabetes-related selective nitrergic neuropathy and associated motility disturbances. Special attention was given to the findings on capillary endothelium and enteric glial cells. Growing evidence indicates that capillary endothelium adjacent to the myenteric ganglia and enteric glial cells surrounding them are determinative in establishing the ganglionic microenvironment. Additionally, recent advances in the development of new strategies to improve glycemic control in type 1 and type 2 diabetes mellitus are also considered in this review. Finally, looking to the future, the recent and promising results of metagenomics for the characterization of the gut microbiome in health and disease such as diabetes are highlighted.