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.

Calcium/calcimimetic via calcium-sensing receptor ameliorates cholera toxin-induced secretory diarrhea in mice

BACKGROUND Enterotoxins produce diarrhea through direct epithelial action and indirectly by activating the enteric nervous system.Calcium-sensing receptor(CaSR)inhibits both actions.The latter has been well documented in vitro but not in vivo.The hypothesis to be tested was that activating CaSR inhibits diarrhea in vivo.AIM To determine whether CaSR agonists ameliorate secretory diarrhea evoked by cholera toxin(CTX)in mice.METHODS CTX was given orally to C57BL/6 mice to induce diarrhea.Calcium and calci-mimetic R568 were used to activate CaSR.To maximize their local intestinal actions,calcium was administered luminally via oral rehydration solution(ORS),whereas R568 was applied serosally using an intraperitoneal route.To verify that their actions resulted from the intestine,effects were also examined on Cre-lox intestine-specific CaSR knockouts.Diarrhea outcome was measured biochemically by monitoring changes in fecal Cl-or clinically by assessing stool consistency and weight loss.RESULTS CTX induced secretory diarrhea,as evidenced by increases in fecal Cl-,stool consistency,and weight loss following CTX exposure,but did not alter CaSR,neither in content nor in function.Accordingly,calcium and R568 were each able to ameliorate diarrhea when applied to diseased intestines.Intestinal CaSR involvement is suggested by gene knockout experiments where the anti-diarrheal actions of R568 were lost in intestinal epithelial CaSR knockouts(villinCre/Casrflox/flox)and neuronal CaSR knockouts(nestinCre/Casrflox/flox).CONCLUSION Treatment of acute secretory diarrheas remains a global challenge.Despite advances in diarrhea research,few have been made in the realm of diarrhea therapeutics.ORS therapy has remained the standard of care,although it does not halt the losses of intestinal fluid and ions caused by pathogens.There is no cost-effective therapeutic for diarrhea.This and other studies suggest that adding calcium to ORS or using calcimimetics to activate intestinal CaSR might represent a novel approach for treating secretory diarrheal diseases.

Study of the roles of caspase-3 and nuclear factor kappa B in myenteric neurons in a P2X7 receptor knockout mouse model of ulcerative colitis

BACKGROUND The literature indicates that the enteric nervous system is affected in inflammatory bowel diseases(IBDs)and that the P2X7 receptor triggers neuronal death.However,the mechanism by which enteric neurons are lost in IBDs is unknown.AIM To study the role of the caspase-3 and nuclear factor kappa B(NF-κB)pathways in myenteric neurons in a P2X7 receptor knockout(KO)mouse model of IBDs.METHODS Forty male wild-type(WT)C57BL/6 and P2X7 receptor KO mice were euthanized 24 h or 4 d after colitis induction by 2,4,6-trinitrobenzene sulfonic acid(colitis group).Mice in the sham groups were injected with vehicle.The mice were divided into eight groups(n=5):The WT sham 24 h and 4 d groups,the WT colitis 24 h and 4 d groups,the KO sham 24 h and 4 d groups,and the KO colitis 24 h and 4 d groups.The disease activity index(DAI)was analyzed,the distal colon was collected for immunohistochemistry analyses,and immunofluorescence was performed to identify neurons immunoreactive(ir)for calretinin,P2X7 receptor,cleaved caspase-3,total caspase-3,phospho-NF-κB,and total NF-κB.We analyzed the number of calretinin-ir and P2X7 receptor-ir neurons per ganglion,the neuronal profile area(μm^(2)),and corrected total cell fluorescence(CTCF).RESULTS Cells double labeled for calretinin and P2X7 receptor,cleaved caspase-3,total caspase-3,phospho-NF-κB,or total NF-κB were observed in the WT colitis 24 h and 4 d groups.The number of calretinin-ir neurons per ganglion was decreased in the WT colitis 24 h and 4 d groups compared to the WT sham 24 h and 4 d groups,respectively(2.10±0.13 vs 3.33±0.17,P<0.001;2.92±0.12 vs 3.70±0.11,P<0.05),but was not significantly different between the KO groups.The calretinin-ir neuronal profile area was increased in the WT colitis 24 h group compared to the WT sham 24 h group(312.60±7.85 vs 278.41±6.65,P<0.05),and the nuclear profile area was decreased in the WT colitis 4 d group compared to the WT sham 4 d group(104.63±2.49 vs 117.41±1.14,P<0.01).The number of P2X7 receptor-ir neurons per ganglion was decreased in the WT colitis 24 h and 4 d groups compared to the WT sham 24 h and 4 d groups,respectively(19.49±0.35 vs 22.21±0.18,P<0.001;20.35±0.14 vs 22.75±0.51,P<0.001),and no P2X7 receptor-ir neurons were observed in the KO groups.Myenteric neurons showed ultrastructural changes in the WT colitis 24 h and 4 d groups and in the KO colitis 24 h group.The cleaved caspase-3 CTCF was increased in the WT colitis 24 h and 4 d groups compared to the WT sham 24 h and 4 d groups,respectively(485949±14140 vs 371371±16426,P<0.001;480381±11336 vs 378365±4053,P<0.001),but was not significantly different between the KO groups.The total caspase-3 CTCF,phospho-NF-κB CTCF,and total NF-κB CTCF were not significantly different among the groups.The DAI was recovered in the KO groups.Furthermore,we demonstrated that the absence of the P2X7 receptor attenuated inflammatory infiltration,tissue damage,collagen deposition,and the decrease in the number of goblet cells in the distal colon.CONCLUSION Ulcerative colitis affects myenteric neurons in WT mice but has a weaker effect in P2X7 receptor KO mice,and neuronal death may be associated with P2X7 receptor-mediated caspase-3 activation.The P2X7 receptor can be a therapeutic target for IBDs.

Enteric nervous system and inflammatory bowel diseases:Correlated impacts and therapeutic approaches through the P2X7 receptor

The enteric nervous system(ENS)consists of thousands of small ganglia arranged in the submucosal and myenteric plexuses,which can be negatively affected by Crohn’s disease and ulcerative colitis-inflammatory bowel diseases(IBDs).IBDs are complex and multifactorial disorders characterized by chronic and recurrent inflammation of the intestine,and the symptoms of IBDs may include abdominal pain,diarrhea,rectal bleeding,and weight loss.The P2X7 receptor has become a promising therapeutic target for IBDs,especially owing to its wide expression and,in the case of other purinergic receptors,in both human and model animal enteric cells.However,little is known about the actual involvement between the activation of the P2X7 receptor and the cascade of subsequent events and how all these activities associated with chemical signals interfere with the functionality of the affected or treated intestine.In this review,an integrated view is provided,correlating the structural organization of the ENS and the effects of IBDs,focusing on cellular constituents and how therapeutic approaches through the P2X7 receptor can assist in both protection from damage and tissue preservation.

Morphological changes in interstitial cells of Cajal in the deep muscular plexus and enteric motor neurons of the intestine in rats with multiple organ dysfunction syndrome

BACKGROUND：Gastrointestinal motility dysfunction in multiple organ dysfunction syndrome （MODS） has been reported to be related to damage to interstitial cells of Cajal （ICC）. In the entedc nervous system, ICC and smooth muscle cells are connected in a network to form a special functional unit. Many gastrointestinal motility dysfunction diseases are associated with damage to this network.OBJECTIVE：To investigate the morphological changes of intestinal ICC, and to explore the mechanisms underlying gastrointestinal motility dysfunction in rats with MODS.DESIGN, TIME AND SE＇I-FING：The randomized, controlled, experiment was performed at the Central Laboratory of the First Affiliated Hospital of Dalian Medical University of China between June 2007 and March 2009.MATERIALS：Escherichia coli （E. colistrain O127 H6） and bovine serum albumin were purchased from Sigma, USA.METHODS：A total of 40 Wistar rats were equally and randomly divided into MODS group and control group. Suspension of E. coil strain O127 H6 containing BaSO4 and saline were sterilely injected into the abdominal cavity of rats in the MODS and control groups, respectively.MAIN OUTCOME MEASURES：Immunohistochemical double-staining and confocal laser scanning microscopy were used to observe the morphological changes in intestinal cholinergic nerves and ICC in the deep muscular plexus network. Electron microscopy was employed to evaluate the ultrastructural features of ICC in the deep muscular plexus of rats with MODS.RESULTS：Compared with the control group, the distributions and densities of cholinergic/nitrergic newes and ICC in the deep muscular plexus were significantly decreased in the MODS group （P 〈 0.01）. The enteric nerve-ICC network were disrupted.CONCLUSION：There is ultrastructural injury in the ICC in the deep muscular plexus and enteric nerves of the intestine in rats with MODS, which may be associated with the dysmotility of the gastrointestinal tract in MODS.

Enteric glia mediate neuronal outgrowth through release of neurotrophic factors

Previous studies have shown that transplanted enteric glia enhance axonal regeneration, reduce tissue damage, and promote functional recovery following spinal cord injury. However, the mechanisms by which enteric glia mediate these beneficial effects are unknown. Neurotrophic factors can promote neuronal differentiation, survival and neurite extension. We hypothesized that enteric glia may exert their protective effects against spinal cord injury partially through the secretion of neurotrophic factors. In the present study, we demonstrated that primary enteric glia cells release nerve growth factor, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor over time with their concentrations reaching approximately 250, 100 and 50 pg/mL of culture medium respectively after 48 hours. The biological relevance of this secretion was assessed by incubating dissociated dorsal root ganglion neuronal cultures in enteric glia-conditioned medium with and/or without neutralizing antibodies to each of these proteins and evaluating the differences in neurite growth. We discovered that conditioned medium enhances neurite outgrowth in dorsal root ganglion neurons. Even though there was no detectable amount of neurotrophin-3 secretion using ELISA analysis, the neurite outgrowth effect can be attenuated by the antibody-mediated neutralization of each of the aforementioned neurotrophic factors. Therefore, enteric glia secrete nerve growth factor, brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor and neurotrophin-3 into their surrounding environment in concentrations that can cause a biological effect.

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.

The crosstalk between enteric nervous system and immune system in intestinal development,homeostasis and diseases

The gut is the largest digestive and absorptive organ,which is essential for induction of mucosal and systemic immune responses,and maintenance of metabolic-immune homeostasis.The intestinal components contain the epithelium,stromal cells,immune cells,and enteric nervous system(ENS),as well as the outers,such as gut microbiota,metabolites,and nutrients.The dyshomeostasis of intestinal microenvironment induces abnormal intestinal development and functions,even colon diseases including dysplasia,inflammation and tumor.Several recent studies have identified that ENS plays a crucial role in maintaining the immune homeostasis of gastrointestinal(GI)microenvironment.The crosstalk between ENS and immune cells,mainly macrophages,T cells,and innate lymphoid cells(ILCs),has been found to exert important regulatory roles in intestinal tissue programming,homeostasis,function,and inflammation.In this review,we mainly summarize the critical roles of the interactions between ENS and immune cells in intestinal homeostasis during intestinal development and diseases progression,to provide theoretical bases and ideas for the exploration of immunotherapy for gastrointestinal diseases with the ENS as potential novel targets.

Transient receptor potential vanilloid 1-immunoreactive signals in murine enteric glial cells

AIM To investigate the possible involvement of transient receptor potential vanilloid 1(TRPV1) in maturation of enteric glial cells(EGCs).METHODS Immunohistochemical and immunocytochemical techniques were used to analyze EGC markers in myenteric plexus(MP) as well as cultured MP cells and EGCs using TRPV1 knockout(KO) mice.RESULTS We detected TRPV1-immunoreactive signals in EGC in the MP of wild-type(WT) but not KO mice. Expression of glial fibrillary acidic protein(GFAP) immunoreactive signals was lower at postnatal day(PD) 6 in KO mice, though the difference was not clear at PD 13 and PD 21. When MP cells were isolated and cultured from isolated longitudinal muscle-MP preparation from WT and KO mice, the yield of KO EGC was lower than that of WT EGC, while the yield of KO and WT smooth muscle cells showed no difference. Addition of BCTC, a TRPV1 antagonist, to enriched EGC culture resulted in a decrease in the protein ratio of GFAP to S100 B, another EGC/astrocyte-specific marker. CONCLUSION These results address the possibility that TRPV1 may be involved in the maturation of EGC, though further studies are necessary to validate this possibility.

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.

Ex vivo effect of vascular wall stromal cells secretome on enteric ganglia

BACKGROUND Mesenchymal stromal cell(MSC)-based therapy is currently under study to treat inflammatory bowel diseases.MSC bioactive products could represent a valid alternative to overcome issues associated with systemic whole-cell therapies.However,MSC anti-inflammatory mechanisms differ between rodents and humans,impairing the reliability of preclinical models.AIM To evaluate the effect of conditioned medium(CM)derived from porcine vascular wall MSCs(pVW-MSCs)on survival and differentiation of porcine and guinea pig enteric ganglia exposed to lipopolysaccharide(LPS).METHODS Primary cultures of enteric ganglia were obtained by mechanic and enzymatic digestion of ileum resections from guinea pigs(Cavia porcellus)(GPEG)and pigs(Suus scrofa)(PEG).pVW-MSCs were derived by enzymatic digestion from vascular wall resections of porcine aorta and tested by immunoflowcytometry for MSC immune profile.Enteric ganglia were treated with increasing concentrations of LPS,CM derived by pVW-MSCs or a combination of CM and LPS 1μg/mL.Cell count and morphometric analysis of HuD positive neurons and glial fibrillary acidic protein positive glial cells were performed by immunofluorecent staining of cultured ganglia.RESULTS PEG showed a higher number of neurons compared to GPEG.Overall,CM exerted a protective role on LPS-treated enteric ganglia.CM in combination with LPS increased the number of glial cells per ganglion in both cultures evoking glial cells differentiation in porcine cultures.CONCLUSION These findings suggest an immunomodulating activity of pVW-MSCs mediators on the enteric nervous system in inflammatory conditions.

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.

Toxoplasma gondii causes death and plastic alteration in the jejunal myenteric plexus

AIM:To assess the effects of ME-49 Toxoplasma gondii(T.gondii) strain infection on the myenteric plexus and external muscle of the jejunum in rats.METHODS:Thirty rats were distributed into two groups:the control group(CG)(n = 15) received 1 m L of saline solution orally, and the infected group(IG)(n=15)inoculated with 1 m L of saline solution containing500 oocysts of M-49 T.gondii strain orally.After 36 d of infection,the rats were euthanized.Infection with T.gondii was confirmed by blood samples collected from all rats at the beginning and end of the experiment.The jejunum of five animals was removed and submitted to routine histological processing(paraffin)for analysis of external muscle thickness.The remaining jejunum from the others animals was used to analyze the general population and the NADH-diaphorase,VIPergic and nitrergic subpopulations of myenteric neurons;and the enteric glial cells(S100-IR).RESULTS:Serological analysis showed that animals from the IG were infected with the parasite.Hypertrophy affecting jejunal muscle thickness was observed in the IG rats(77.02±42.71)in relation to the CG(51.40±12.34),P<0.05.In addition,31.2%of the total number of myenteric neurons died(CG:39839.3±5362.3;IG:26766.6±2177.6;P<0.05);hyperplasia of nitrergic myenteric neurons was observed(CG:7959.0±1290.4;IG:10893.0±1156.3;P<0.05);general hypertrophy of the cell body in the remaining myenteric neurons was noted[CG:232.5(187.2-286.0);IG:248.2(204.4-293.0);P<0.05];hypertrophy of the smallest varicosities containing VIP neurotransmitter was seen(CG:0.46±0.10;IG:0.80±0.16;P<0.05)and a reduction of 25.3%in enteric glia cells(CG:12.64±1.27;IG:10.09±2.10;P<0.05)was observed in the infected rats.CONCLUSION:It was concluded that infection with oocysts of ME-49 T.gondii strain caused quantitative and plastic alterations in the myenteric plexus of the jejunum in rats.

Structure of the myenteric plexus in normal and diseased human ileum analyzed by X-ray virtual histology slices

BACKGROUND The enteric nervous system(ENS)is situated along the entire gastrointestinal tract and is divided into myenteric and submucosal plexuses in the small and large intestines.The ENS consists of neurons,glial cells,and nerves assembled into ganglia,surrounded by telocytes,interstitial cells of Cajal,and connective tissue.Owing to the complex spatial organization of several interconnections with nerve fascicles,the ENS is difficult to examine in conventional histological sections of 3-5μm.AIM To examine human ileum full-thickness biopsies using X-ray phase-contrast nanotomography without prior staining to visualize the ENS.METHODS Six patients were diagnosed with gastrointestinal dysmotility and neuropathy based on routine clinical and histopathological examinations.As controls,fullthickness biopsies were collected from healthy resection ileal regions after hemicolectomy for right colon malignancy.From the paraffin blocks,4-μm thick sections were prepared and stained with hematoxylin and eosin for localization of the myenteric ganglia under a light microscope.A 1-mm punch biopsy(up to 1 cm in length)centered on the myenteric plexus was taken and placed into a Kapton®tube for mounting in the subsequent investigation.X-ray phase-contrast tomography was performed using two custom-designed laboratory setups with micrometer resolution for overview scanning.Subsequently,selected regions of interest were scanned at a synchrotron-based end-station,and high-resolution slices were reported.In total,more than 6000 virtual slices were analyzed from nine samples.RESULTS In the overview scans,the general architecture and quality of the samples were studied,and the myenteric plexus was localized.High-resolution scans revealed details,including the ganglia,interganglional nerve fascicles,and surrounding tissue.The ganglia were irregular in shape and contained neurons and glial cells.Spindle-shaped cells with very thin cellular projections could be observed on the surface of the ganglia,which appeared to build a network.In the patients,there were no alterations in the general architecture of the myenteric ganglia.Nevertheless,several pathological changes were observed,including vacuolar degeneration,autophagic activity,the appearance of sequestosomes,chromatolysis,and apoptosis.Furthermore,possible expulsion of pyknotic neurons and defects in the covering cellular network could be observed in serial slices.These changes partly corresponded to previous light microscopy findings.CONCLUSION The analysis of serial virtual slices could provide new information that cannot be obtained by classical light microscopy.The advantages,disadvantages,and future possibilities of this method are also discussed.

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.

Downregulation of metabotropic glutamate receptors mGluR5 and glutamate transporter EAAC1 in the myenteric plexus of the diabetic rat ileum

Objective： To study the morphologic abnormalities of the myenteric plexus in diabetic rats and to explore the mechanism of their effect on gastrointestinal motility. Methods： Forty rats were randomly divided into a diabetic group and a control group, Gastric emptying and small intestine transit rates were measured and histologic and molecular changes in glutamatergic nerves in the ileal myenteric plexus were observed, mGluR5 receptor and EAAC1 transporter changes in the diabetic rats were studied using fluorescence immunohistochemistry and RT-PCR. Results：Eighteen weeks after the establishment of the diabetic rats model, gastric emptying and small intestine transit rates were found to be significantly delayed in the diabetic group when compared with the control group. The density of glutamatergic ganglia and neurons in the ileal myenterie plexus were significantly decreased in the diabetic group when compared with control group（P 〈 0.05） and the mGluR5 receptors and EAAC1 transporters were downregulated in the diabetic rats（P 〈 0.05）. Conclusion： Decreased glutamatergic enteric ganglia and neurons and decreased mGluR5 receptors and EAAC1 transporters in the intestinal myenteric plexus is one of the mechanisms of diabetic gastroenteropathy in rats.

Analyzing the Prebiotic Potential of Glucosamine for Targeting the Gut Microbiome Health

Recognizing the composition and modulation of the microbiome, a viable therapeutic tool for multi-targeted therapy is a new strategy that has recently been explored. Glucosamine (GS) is being studied for its prebiotic potential in addition to being the most abundant and naturally occurring amino monosaccharide. The current study focuses on glucosamine’s prebiotic potential by assessing the stability of various GS concentrations (1% - 5%) in the gastrointestinal tract (GIT) and its ability to be fermented by the gut microbiota. The results showed that GS stimulated the most growth in L. acidophilus even after a longer incubation time than B. bifidum and L. acidophilus growth was concentration-dependent, with maximum growth at 3% with a simultaneous decrease in pH (5.6 - 1.7). The decrease in GS concentration with time also represented the growth of bacterial species, demonstrating the species’ utilization of GS. Furthermore, at 3%, GS also represented the prebiotic index of 1.9. In addition, the concentration of GS in various simulated GIT fluids was estimated in both fast and fed conditions to examine GS stability at various levels in the gut. The results showed that GS remained unaffected and non-digestible in all of the simulated GIT fluids (salivary, gastric, intestinal, and colonic), but there was a slight decrease in GS concentration (2.8%) in the fasted state of gastric fluid due to low pH levels (1.6). As a result, the findings are conclusive and suggest that GS possesses prebiotic properties.

贲门癌根治性全胃切除术后Roux-en-Y滞留综合征的研究

目的分析贲门癌全胃切除术后Roux-en-Y滞留综合征发生的原因及其防治。方法回顾性分析57例贲门癌根治性全胃切除术后发生Roux-en-Y滞留综合征患者的临床资料。结果 57例患者中51例获得随访,其中8例出现明显的胃肠道症状:2例出现单纯的恶心、呕吐;3例出现腹痛、腹胀,进食后症状加重;3例出现腹痛、腹胀同时伴恶心、呕吐。7例证实为Roux-en-Y滞留综合征,1例为肿瘤复发。术后Roux-en-Y滞留综合征发病率为13.7%(7/51),7例患者均行保守治疗。结论 Roux-en-Y滞留综合征的发生与Roux肠袢的长度及是否全胃切除有关,术后早期应用肠内营养剂及低剂量红霉素可预防其发生。

改良胆肠Warren吻合术202例疗效观察

目的 比较改良胆肠Warren吻合术较胆肠Roux-en-Y吻合术的优越性.方法 2004-05～2013-10在本院外科住院的202例患者,其中胆肠Roux-en-Y吻合术病例123例,改良胆肠Warren吻合术病例79例,观察患者术后胆道感染的发生率和再手术率.结果 术后随访180例,随访率89.1％;随访时间3～70月,平均35.6±19.3月.胆肠Roux-en-Y吻合术后胆道感染率11.1％,再手术率5.6％;改良胆肠Warren吻合术后胆道感染率5.6％,再手术率1.4％,两组间差异有统计学意义（P＜0.05）.结论 改良胆肠Warren吻合术术后的胆道感染率较胆肠Roux-en-Y吻合术明显减少,且手术操作简便、省时,术后并发症少,值得推广.

The Gut Brain Connection

The gut-brain connection is a bidirectional communication system that links the gut microbiome to the central nervous system (CNS). The gut-brain axis communicates through a variety of mechanisms, including the release of hormones, neurotransmitters, and cytokines. These signaling molecules can travel from the gut to the brain and vice versa, influencing various physiological and cognitive functions. Emerging therapeutic strategies targeting the gut-brain connection include probiotics, prebiotics, and faecal microbiota transplantation (FMT). Probiotics are live microorganisms that are similar to the beneficial bacteria that are naturally found in the gut. Prebiotics are non-digestible fibers that feed the beneficial bacteria in the gut. FMT is a procedure in which faecal matter from a healthy donor is transplanted into the gut of a person with a diseased microbiome. Probiotics, prebiotics, and FMT have been shown to be effective in treating a variety of gastrointestinal disorders, and there is growing evidence that they may also be effective in treating neurological and psychiatric disorders. This review explores the emerging field of the gut-brain connection, focusing on the communication pathways between the gut microbiome and the central nervous system. We summarize the potential roles of gut dysbiosis in various neurological and psychiatric disorders. Additionally, we discuss potential therapeutic strategies, research limitations, and future directions in this exciting area of research. More research is needed to fully understand the mechanisms underlying the gut-brain connection and to develop safe and effective therapies that target this pathway. However, the findings to date are promising, and there is the potential to revolutionize the way we diagnose and treat a variety of neurological and psychiatric disorders.