Umbilical cord mesenchymal stem cell exosomes alleviate necrotizing enterocolitis in neonatal mice by regulating intestinal epithelial cells autophagy

BACKGROUND Necrotizing enterocolitis(NEC)is a severe gastrointestinal disease that affects premature infants.Although mounting evidence supports the therapeutic effect of exosomes on NEC,the underlying mechanisms remain unclear.AIM To investigate the mechanisms underlying the regulation of inflammatory response and intestinal barrier function by umbilical cord mesenchymal stem cell(UCMSCs)exosomes,as well as their potential in alleviating NEC in neonatal mice.METHODS NEC was induced in 5-d-old C57BL/6 pups through hypoxia and gavage feeding of formula containing lipopolysaccharide(LPS),after which the mice received human UCMSC exosomes(hUCMSC-exos).The control mice were allowed to breastfeed with their dams.Ileal tissues were collected from the mice and analyzed by histopathology and immunoblotting.Colon tissues were collected from NEC neonates and analyzed by immunofluorescence.Molecular biology and cell culture approaches were employed to study the related mechanisms in intestinal epithelial cells.RESULTS We found that autophagy is overactivated in intestinal epithelial cells during NEC,resulting in reduced expression of tight junction proteins and an increased inflammatory response.The ability of hUCMSC-exos to ameliorate NEC in a mouse model was dependent on decreased intestinal autophagy.We also showed that hUCMSC-exos alleviate the inflammatory response and increase migration ability in intestinal epithelial cells induced by LPS.CONCLUSION These results contribute to a better understanding of the protective mechanisms of hUCMSC-exos against NEC and provide a new theoretical and experimental foundation for NEC treatment.These findings also enhance our understanding of the role of the autophagy mechanism in NEC,offering potential avenues for identifying new therapeutic targets.

Diagnostic significance of serum levels of serum amyloid A,procalcitonin,and high-mobility group box 1 in identifying necrotising enterocolitis in newborns

BACKGROUND Necrotising enterocolitis(NEC)is a critical gastrointestinal emergency affecting premature and low-birth-weight neonates.Serum amyloid A(SAA),procalcitonin(PCT),and high-mobility group box 1(HMGB1)have emerged as potential biomarkers for NEC due to their roles in inflammatory response,tissue damage,and immune regulation.AIM To evaluate the diagnostic value of SAA,PCT,and HMGB1 in the context of NEC in newborns.METHODS The study retrospectively analysed the clinical data of 48 newborns diagnosed with NEC and 50 healthy newborns admitted to the hospital.Clinical,radiological,and laboratory findings,including serum SAA,PCT,and HMGB1 Levels,were collected,and specific detection methods were used.The diagnostic value of the biomarkers was evaluated through statistical analysis,which was performed using chi-square test,t-test,correlation analysis,and receiver operating characteristic(ROC)analysis.RESULTS The study demonstrated significantly elevated levels of serum SAA,PCT,and HMGB1 Levels in newborns diagnosed with NEC compared with healthy controls.The correlation analysis indicated strong positive correlations among serum SAA,PCT,and HMGB1 Levels and the presence of NEC.ROC analysis revealed promising sensitivity and specificity for serum SAA,PCT,and HMGB1 Levels as potential diagnostic markers.The combined model of the three biomarkers demonstrating an extremely high area under the curve(0.908).CONCLUSION The diagnostic value of serum SAA,PCT,and HMGB1 Levels in NEC was highlighted.These biomarkers potentially improve the early detection,risk stratification,and clinical management of critical conditions.The findings suggest that these biomarkers may aid in timely intervention and the enhancement of outcomes for neonates affected by NEC.

Research Progress on the Etiology,Diagnosis and Treatment of Neonatal Necrotizing Enterocolitis

Necrotizing enterocolitis(NEC)is a leading cause of death from gastrointestinal disease in premature and low-birth-weight infants.Early detection of severely ischemic or necrotic bowel before perforation is rather difficult.New techniques including multi-omics contribute to better understanding its underlying mechanisms and discovering differe categories of biomarkers.Combination of clinical metrics such as seven components of metabolic derangement(CMD)may provide accurate assessment of its severity.Implementation of quality improvement initiatives including breast milk feeding actually lowers its incidence.

Non-clostridium difficile induced pseudomembranous colitis

Pseudomembranous colitis is severe inflammation of the inner lining of the colon due to anoxia,ischemia,endothelial damage,and toxin production.The majority of cases of pseudomembranous colitis are due to Clostridium difficile.However,other causative pathogens and agents have been responsible for causing a similar pattern of injury to the bowel with the endoscopic appearance of yellow-white plaques and membranes on the mucosal surface of the colon.Common presenting symptoms and signs include crampy abdominal pain,nausea,watery diarrhea that can progress to bloody diarrhea,fever,leukocytosis,and dehydration.Negative testing for Clostridium difficile or failure to improve on treatment should prompt evaluation for other causes of pseudomembranous colitis.Bacterial infections other than Clostridium difficile,Viruses such as cytomegalovirus,parasitic infections,medications,drugs,chemicals,inflammatory diseases,and ischemia are other differential diagnoses to look out for in pseudomembranous colitis.Complications of pseudomembranous colitis include toxic megacolon,hypotension,colonic perforation with peritonitis,and septic shock with organ failure.Early diagnosis and treatment to prevent progression are important.The central perspective of this paper is to provide a concise review of the various etiologies for pseudomembranous colitis and management per prior literature.

Efficacy of peritoneal drainage in very-low-birth-weight neonates with Bell’s stage II necrotizing enterocolitis:A single-center retrospective study

BACKGROUND Currently,pediatric surgeons are challenged by a lack of consensus on the optimal management strategy(conservative or surgical)for children with Bell’s stage II necrotizing enterocolitis(NEC).AIM To evaluate the clinical efficacy of peritoneal drainage in very-low-birth-weight(VLBW)neonates with modified Bell’s stage II NEC.METHODS This was a retrospective analysis of 102 NEC(modified Bell’s stage II)neonates born with VLBW who were treated at the Fujian Children’s Hospital(Fujian Branch of Shanghai Children’s Medical Center)between January 2017 and January 2020;these included 24 cases in the peritoneal drainage group,36 cases in the exploratory laparotomy group,and 42 cases in the conservative treatment group.RESULTS The general characteristics were comparable in the three groups(P>0.05).Compared with conservative treatment,peritoneal drainage was associated with significantly shorter fasting time,abdominal distension relief time,fecal occult blood(OB)negative conversion time,and reduced hospital length of stay(HLOS)(P<0.05 for all).Despite some advantages of peritoneal drainage over conservative treatment in terms of cure,conversion to laparotomy,intestinal perforation,intestinal stenosis,and abdominal abscess rates,the differences were not statistically significant(P>0.05).Compared to exploratory laparotomy,the fecal OB negative conversion time was significantly shorter in the peritoneal drainage group(P<0.05);similarly,the exploratory laparotomy group showed longer fasting time,abdominal distension relief time,HLOS,and higher complication rate compared to peritoneal drainage group,but the between-group differences were not statistically significant(P>0.05).CONCLUSION Peritoneal drainage,an easy-to-operate procedure,can improve the clinical symptoms of VLBW neonates with Bell’s stage II NEC and help reduce the HLOS.

Localized pseudomembranous colitis in the cecum and ascending colon mimicking acute appendicitis

A 61-year-old male was admitted to our hospital due to right lower abdominal pain and watery diarrhea for 3 d.Beginning 3 wk before he arrived in our hospital,he took 3 rd-generation cephalosporin(cefixime) for 2 wk due to chronic left ear otitis media.Colonoscopic examination revealed yellowish patches of ulcerations and swelling covered with thick serosanguineous exudate in the cecum and ascending colon.After 7 d of oral metronidazole treatment,his symptoms completely disappeared.We report a case of localized pseudomembranous colitis in the cecum and ascending colon mimicking acute appendicitis associated with cefixime.

Pseudomembranous colitis associated with a triple therapy for Helicobacter pylori eradication

Helicobacter pylori(H.pylori)is one of the most common chronic bacterial infections in humans,affecting half of world’s population.Therapy for H.pylori infection has proven to be both effective and safe.The oneweek triple therapy including proton pump inhibitor,clarithromycin,and amoxicillin or metronidazole is still recommended as a first-line treatment to eradicate H.pylori infection in countries with low clarithromycin resistance.Generally,this therapy is well-tolerated,with only a few and usually minor side effects.However,rare but severe adverse effects such as pseudomembranous colitis have been reported,Clostridium difficile(C.difficile)infection being the main causative factor in all cases.We report the cases of two women who developed pseudomembranous colitis after a 1-wk triple therapy consisting of pantoprazole 20 mg bid,clarithromycin 500 mg bid,and amoxicillin 1 g bid to eradicate H.pylori infection.A limited colonoscopy showed typical appearance of pseudomembranous colitis,and the stool test for C.difficile toxins was positive.Rapid resolution of symptoms and negative C.difficile toxins were obtained in both patients with oral vancomycin.No relapse occurred during a four and eleven-month,respectively,follow up.These cases suggest that physicians should have a high index of suspicion for pseudomembranous colitis when evaluate patients with diarrhea following H.pylori eradication therapy.

Colonic ulcerations may predict steroid-refractory course in patients with ipilimumab-mediated enterocolitis

AIM To investigate management of patients who develop ipilimumab-mediated enterocolitis, including association of endoscopic findings with steroid-refractory symptoms and utility of infliximab as second-line therapy.METHODS We retrospectively reviewed all patients at our centerwith metastatic melanoma who were treated with ipilimumab between March 2011 and May 2014. All patients received a standard regimen of intravenous ipilimumab 3 mg/kg every 3 wk for four doses or until therapy was stopped due to toxicity or disease progression. Basic demographic and clinical data were collected on all patients. For patients who developed grade 2 or worse diarrhea(increase of 4 bowel movements per day), additional data were collected regarding details of gastrointestinal symptoms, endoscopic findings and treatment course. Descriptive statistics were used.RESULTS A total of 114 patients were treated with ipilimumab during the study period and all were included. Sixteen patients(14%) developed ≥ grade 2 diarrhea. All patients were treated with high-dose corticosteroids(1-2 mg/kg prednisone daily or equivalent). Nine of 16 patients(56%) had ongoing diarrhea despite highdose steroids. Steroid-refractory patients received one dose of intravenous infliximab at 5 mg/kg, and all but one had brisk resolution of diarrhea. Fourteen of the patients underwent either colonoscopy or sigmoidoscopy with variable endoscopic findings, ranging from mild erythema to colonic ulcers. Among 8 patients with ulcers demonstrated by sigmoidoscopy or colonoscopy, 7 patients(88%) developed steroidrefractory symptoms requiring infliximab. With a median follow-up of 264 d, no major adverse events associated with prednisone or infliximab were reported.CONCLUSION In patients with ipilimumab-mediated enterocolitis, the presence of colonic ulcers on endoscopy was associated with a steroid-refractory course.

Induction of Necrotizing Enterocolitis in Non-Premature Sprague-Dawley Rats and the Effect of Administering Breast Milk-Isolated <i>Lactobacillus salivarius</i>LPLM-O1

Due to an increasing incidence of necrotizing enterocolitis (NEC), as well as its associated mortality and long-term complications seen in surviving patients, the main focus of research in NEC has shifted to the prevention and treatment of the disease. The hypothesis of this work is that the strain Lactobacillus salivarius LPLM-O1 can decrease the intestinal injuries in a model of induced NEC. 26 newborn Sprague-Dawley pups were used in this study and randomized in three groups: control group (n = 6), which were fed with infant formula (Similac NeosureTM, Abbott);probiotic group (n = 10), which were fed with the same infant formula but fortified with 109 colony-forming units (CFU) of Lactobacillus salivarius LPLM-O1, and the NEC-induced group (n = 10). Each group was fed with 100 μl of food formula every three hours, using a modified syringe. The probiotic and NEC groups were exposed to asphyxia- and cold-induced stress to develop experimental NEC. At the end of the experiment (96 hrs), animals were sacrificed, and their small intestines were carefully removed and evaluated for typical signs of NEC, microbiological count and histological analyses. The histological analysis of the NEC-induced group showed transmural necrosis (grade 4);in the probiotic group, the grade was comparatively lower (grade 2). Survival ratewas higher in the probiotic group (83%) than in the NEC-induced group (46%);however, the difference in not statistically significant (p = 0.14). Lactic acid bacteria counts were higher in the probiotic group than in the NEC-induced group (8.4 × 108 and 6.1 × 107 CFU/intestine tissue gram, respectively). According to these results, the model of artificial induction of NEC was effectively establishedin all pups, and the probiotic strain slightly decreases the injuries’ grade in newborn pups.

Role of LPS/CD14/TLR4-mediated inflammation in necrotizing enterocolitis:Pathogenesis and therapeutic implications

AIM:To establish the roles of lipopolysaccharide (LPS)/CD14/toll-like receptor 4 (TLR4)-mediated inflammation in a rat model of human necrotizing enterocolitis (NEC).METHODS: Six pairs of intestinal samples from human NEC were collected before and after recovery for histological and molecular analysis of inflammatory cytokines and signaling components. In the rat NEC model, we isolated 10-cm jejunum segments and divided them into six groups (n=6) for sham operation, treatment with LPS, bowel distension, combined bowel distension and LPS stimulation, and two therapeutic groups. The potential eff icacy of a recombinant CD18 peptide and a monoclonal CD14 antibody was evaluated in the latter two groups. The serum and tissue levels of several inflammatory mediators were quantified by real-time polymerase chain reaction, ELISA and immunoblotting.RESULTS: Human acute phase NEC tissues displayed significant increases (P<0.05) in levels of TLR4, CD14, myeloid differentiation protein (MD)-2, tumor necrosis factor (TNF)-α and nuclear factor-κB when compared to those after recovery. The histological and inflammatory picture of human NEC was reproduced in rats that were treated with combined bowel distension and LPS, but not in the sham-operated and other control rats. Serum levels of interleukin-6 and TNF-α were also elevated. The NEC pathology was attenuated by treating the NEC rats with a monoclonal CD14 antibody or an LPS-neutralizing peptide.CONCLUSION:LPS and distension are required to produce the histological and inflammatory features of NEC. A potential treatment option is blocking LPS activation and leukocyte infi ltration.

Necrotizing enterocolitis: A multifactorial disease with no cure

Necrotizing enterocolitis is an inflammatory bowel disease of neonates with significant morbidity and mortality in preterm infants. Due to the multifactorial nature o the disease and limitations in disease models, early diagnosis remains challenging and the pathogenesis elusive. Although preterm birth, hypoxic-ischemic events formula feeding, and abnormal bacteria colonization are established risk factors, the role of genetics and vasoactive/inflammatory mediators is unclear Consequently, treatments do not target the specific underlying disease processes and are symptomatic and surgically invasive. Breast-feeding is the most effective preventative measure. Recent advances in the prevention of necrotizing enterocolitis have focused on bioactive nutrients and trophic factors in human milk. Developmen of new disease models including the aspect of prematurity that consistently predisposes neonates to the disease with multiple risk factors will improve our understanding of the pathogenesis and lead to discovery of innovative therapeutics.

Neutropenic enterocolitis

Neutropenic colitis is a severe condition usually affecting immunocompromised patients. Its exact pathogenesis is not completely understood. The main elements in disease onset appear to be intestinal mucosal injury together with neutropenia and the weakened immune system of the afflicted patients. These initial conditions lead to intestinal edema, engorged vessels, and a disrupted mucosal surface, which becomes more vulnerable to bacterial intramural invasion. Chemotherapeutic agents can cause direct mucosal injury (mucositis) or can predispose to distension and necrosis, thereby altering intestinal motility. This article aims to review current concepts regarding neutropenic colitis&#x02019; pathogenesis, diagnosis, and management.

Pseudomembranous colitis presenting as acute colonic obstruction without diarrhea in a patient with gastric Burkitt lymphoma

Pseudomembranous colitis (PMC) usually manifests asfever and diarrhea in hospitalized patients treated withsystemic antibiotics. We described a case of PMC withintestinal obstruction but without diarrhea. A 60-yearold man was hospitalized for chemotherapy for the treatment of Burkitt lymphoma of the stomach. The patient became febrile and complained of crampy abdominal pain during the post-chemotherapy nadir. Plain abdominal radiography showed some intestinal gas and niveau. Because stool cytotoxin assay for clostridium difficile was positive and colon fiberscopic examination showed a pseudomembrane at the left side of the colon,and a diagnosis of PMC was made. Treatment with intracolonic vancomycin administration by colonoscopy and nasoileus tube was successful. Physicians should take into account the possibility of bowel obstruction due to PMC occurring in patients undergoing chemotherapy and perform emergency colonoscopy examination of suspected cases.

Prevention of necrotizing enterocolitis in premature infants——an updated review

Necrotizing enterocolitis(NEC) is among the most common and devastating diseases encountered in premature infants, yet the true etiology continues to be poorly understood despite decades of research. Recently, gut bacterial dysbiosis has been proposed as a risk factor for the development of NEC. Based on this theory, several best clinical practices designed to reduce the risk of NEC have been proposed and/or implemented. This review summarizes the results of recent clinical trials and meta-analyses that support some of the existing clinical practices for reducing the risk of NEC in premature infants. It is evident that human milk feeding can reduce the incidence of NEC. While most of the studies demonstrated that probiotic supplementation can significantly reduce the incidence of NEC in premature infants, there are still some concerns regarding the quality, safety, optimal dosage, and treatment duration of probiotic preparations. Antibiotic prophylaxis does not reduce the incidence of NEC, and prolonged initial empirical use of antibiotics might in fact increase the risk of NEC for high-risk premature infants. Lastly, standardized feeding protocols are strongly recommended, both for prevention of postnatal growth restriction and NEC.

New Frontiers of Necrotizing Enterocolitis: From Pathophysiology to Treatment

Necrotizing enterocolitis [NEC] is an inflammatory disease of intestine largely occuring in preterm infants with a wide range of damage from minimal injury limited to mucosa to extensive necrosis of bowel wall and perforation. Despite advancements in neonatal care, mortality remains high [30% - 50%] and controversy still persists with regards to the most appropriate management of neonates with necrotizing enterocolitis. The main factors thought to be involved in the pathogenesis of NEC are: relatively hyper-reactive state of premature intestine, enteral feeding and bacterial colonization. In this review, we discuss current knowledge about the epidemiology, pathophysiology, imaging, medical and surgical management of necrotizing enterocolitis and describe novel strategies for prevention and treatment.

Application of prolonging small feeding volumes early in life to prevent of necrotizing enterocolitis in very low birth weight preterm infants

Objective:To study the effects of prolonging small feeding volumes early in life on the incidence of necrotizing enterocolitis(NEC)in very low birth weight(VLBW)preterm infants.Methods:A total of 128 VLBW infants who could not be breastfed were assigned into the experimental group(63 cases)and the control group(65 cases)using a random number table.The experiment group was fed 12 mL/(kg·d)on day 1 which was increased to 24 mL/(kg·d)for the first 10 study days.The control group was fed 12 mL/(kg·d)for the first 14e48 hours.Then,the feeding volume increased by 24-36 mL/(kg·d)up to 140e160 mL/(kg·d)and maintained until the 10th day after birth.The incidence of feeding intolerance and NEC,duration of hospitalization,time to full enteral feedings,incidence of intrahepatic cholestasis,and the levels of gastrin and motilin in serum were assessed.Results:The incidence of feeding intolerance was significantly lower in the experimental group compared with the control group(15.87% vs.33.84%).There was a significant reduction in the incidence of NEC between the experimental and control groups(7.9% vs.16% in the control group).Conclusion:A protocol that prolongs small feeding volumes early in life can reduce the incidence and severity of NEC,but still warrants further study.

Ischemic enterocolitis examined by colonoscopy and selective angiography

AIM: To study the value of colonoscopy and selective angiography in diagnosing ischemic enterocolitis.METHODS: Among the 16 cases under study, 10 cases had hypertension and a history of coronary artery disease (one was hospitalized for sub-ventricular-wall infarction). The blood pressure of 10 of the 16 cases ranged from 13.9-23.8 to 13.3-14.6 kPa (170-180/100-110 mmHg). Two cases had chronic auricular fibrillation, and in four cases, a cardiogram showed left-front branch conduction block. Sixteen patients were examined by colonoscopy. Among them, 14 cases had a long course of angiocardiac disease, and were further examined by selective mesenteric inferior angiography.RESULTS: The colonoscopy revealed local mucous hyperemia edema and blood on contact. Lesions were found in the sigmoid colon in four cases, in the descending colon in eight cases and in splenic flexure in four cases, which suggests that the lesion always appeared in the left part of colon. There were different degrees of inflammatory cell infiltration, submucous bleeding, edema, fibro-embolism and hemosiderosis by biopsy in the 16 patients whose membranes affect part of the enteral wall. Of the 14 patients examined by mesenteric inferior angiography, 3 cases showed mesenteric amphraxis inferior and formation of collateral circulation. There were different degrees of stenosis in the other 11 subjects' mesenteric inferior cavities which grew slim and their branches were stenotic, so the radiographic image was not complete and the ends of some branches even cannot be seen. CONCLUSION: The colonoscopy and the selective mesenteric inferior angiography are both helpful in the diagnosis of ischemic enterocolitis.

Mucin 1 and interleukin-11 protein expression and inflammatory reactions in the intestinal mucosa of necrotizing enterocolitis children after surgery

BACKGROUND Necrotizing enterocolitis(NEC)of the newborn is a frequently occurring clinical disease in infants.The mortality rate of NEC in premature infants is as high as 50%,and the morbidity rate is on the rise.NEC has already caused serious impacts on newborn survival and poses serious threats to both children and families.AIM To investigate the expression and significance of mucin 1(MUC1)and interleukin-11(IL-11)in the intestinal mucosa of infants with neonatal NEC after surgery.METHODS Forty-eight postoperative intestinal mucosal specimens from children with NEC(NEC group)and twenty-two intestinal mucosal specimens from children with congenital intestinal atresia(control group)were collected in our hospital.Immunohistochemical staining and Western blot analysis were used to examine the protein expression of MUC-1 and IL-11 in the two groups.The serum levels of tumor necrosis factor-α(TNF-α)and IL-1βin the two groups were measured by enzyme-linked immunosorbent assay,and the relationship between MUC-1 and IL-11 protein expression and serum TNF-αand IL-1βlevels was analyzed by the linear correlation method.RESULTS The protein expression of MUC-1 and IL-11 in the NEC group was significantly lower than that in the control group,and the difference was statistically significant(P<0.05).The levels of serum TNF-αand IL-1βin the NEC group were significantly higher than those in the control group(P<0.05).The protein expression of MUC-1 and IL-11 in the NEC group negatively correlated with serum TNF-αand IL-1βlevels(P<0.05).There was a significant negative correlation between the protein expression of MUC-1 and IL-11 and the levels of serum TNF-αand IL-1βin the NEC group.CONCLUSION The protein expression of MUC1 and IL-11 in the intestinal mucosa of children with NEC is significantly downregulated after surgery.This downregulation may be involved in the pathogenesis of this disease and has a certain correlation with inflammatory response factors in children with NEC.

Neonatal necrotizing enterocolitis caused by umbilical arterial catheter-associated abdominal aortic embolism:A case report

BACKGROUND Reports of necrotizing enterocolitis(NEC)caused by umbilical arterial catheter(UAC)-associated abdominal aortic embolism in neonates are rare.Herein,we report the case of an extremely low birth weight(ELBW)infant with NEC caused by UAC-associated abdominal aortic embolism.CASE SUMMARY A female infant,aged 21 min and weighing 830 g at 28+6 wk of gestational age,was referred to our hospital because of premature birth and shallow breathing.The patient was diagnosed with ELBW,neonatal respiratory distress syndrome,neonatal intrauterine infection,and neonatal asphyxia.Umbilical arterial and venous catheters were inserted on the day after birth and were removed 9 d later,according to the doctor’s plan.Within 48 h after extubation,the patient’s manifestations included poor responsiveness,heart rate range of 175-185/min,and currant jelly stool.Therefore,we considered a diagnosis of NEC.To determine the cause,we used B-mode ultrasound,which revealed a partial abdominal aortic embolism(2 cm×0.3 cm)and abdominal effusion.The patient was treated with nil per os,gastrointestinal decompression,anti-infective therapy,blood transfusion,and low-molecular-weight heparin sodium q12h for anticoagulant therapy(from May 20 to June 1,the dosage of low-molecular-weight heparin sodium was adjusted according to the anti-Xa activity during treatment).On the 67th day after admission,the patient fully recovered and was discharged.CONCLUSION The abdominal aortic thrombosis in this patient was considered to be catheter related,which requires immediate treatment once diagnosed.The choice of treatment should be determined according to the location of the thrombus and the patient’s condition.

Hirschsprung's disease associated enterocolitis:A comprehensive review

Hirschsprung’s disease(HSCR)is a congenital disorder characterized by failure of the neural crest cells to migrate and populate the distal bowel during gestation affecting different lengths of intestine leading to a distal functional obstruction.Surgical treatment is needed to correct HSCR once the diagnosis is confirmed by demonstrating the absence of ganglion cells or aganglionosis of the affected bowel segment.Hirschsprung’s disease associated enterocolitis(HAEC)is an inflammatory complication associated with HSCR that can present either in the pre-or postoperative period and associated with increased morbidity and mortality.The pathogenesis of HAEC remains poorly understood,but intestinal dysmotility,dysbiosis and impaired mucosal defense and intestinal barrier function appear to play a significant role.There is no clear definition for HAEC,but the diagnosis is primarily clinical,and treatment is guided based on severity.Here,we aim to provide a comprehensive review of the clinical presentation,etiology,pathophysiology,and current therapeutic options for HAEC.