Interplay between creeping fat and gut microbiota: A brand-new perspective on fecal microbiota transplantation in Crohn's disease

Inflammatory bowel disease,particularly Crohn's disease(CD),has been linked to modifications in mesenteric adipose tissue(MAT)and the phenomenon known as"creeping fat"(CrF).The presence of CrF is believed to serve as a predictor for early clinical recurrence following surgical intervention in patients with CD.Notably,the incorporation of the mesentery during ileocolic resection for CD has been correlated with a decrease in surgical recurrence,indicating the significant role of MAT in the pathogenesis of CD.While numerous studies have indicated that dysbiosis of the gut microbiota is a critical factor in the development of CD,the functional implications of translocated microbiota within the MAT of CD patients remain ambiguous.This manuscript commentary discusses a recent basic research conducted by Wu et al.In their study,intestinal bacteria from individuals were transplanted into CD model mice,revealing that fecal microbiota trans-plantation(FMT)from healthy donors alleviated CD symptoms,whereas FMT from CD patients exacerbated these symptoms.Importantly,FMT was found to affect intestinal permeability,barrier function,and the levels of proinflammatory factors and adipokines.Collectively,these findings suggest that targeting MAT and CrF may hold therapeutic potential for patients with CD.However,the study did not evaluate the composition of the intestinal microbiota of the donors or the subsequent alterations in the gut microbiota.Overall,the gut microbiota plays a crucial role in the histopathology of CD,and thus,targeting MAT and CrF may represent a promising avenue for treatment in this patient population.

Computed tomography enterography-based radiomics for assessing mucosal healing in patients with small bowel Crohn's disease

BACKGROUND Mucosal healing(MH)is the major therapeutic target for Crohn's disease(CD).As the most commonly involved intestinal segment,small bowel(SB)assessment is crucial for CD patients.Yet,it poses a significant challenge due to its limited accessibility through conventional endoscopic methods.AIM To establish a noninvasive radiomic model based on computed tomography enterography(CTE)for MH assessment in SBCD patients.METHODS Seventy-three patients diagnosed with SBCD were included and divided into a training cohort(n=55)and a test cohort(n=18).Radiomic features were obtained from CTE images to establish a radiomic model.Patient demographics were analysed to establish a clinical model.A radiomic-clinical nomogram was constructed by combining significant clinical and radiomic features.The diagnostic efficacy and clinical benefit were evaluated via receiver operating characteristic(ROC)curve analysis and decision curve analysis(DCA),respectively.RESULTS Of the 73 patients enrolled,25 patients achieved MH.The radiomic-clinical nomogram had an area under the ROC curve of 0.961(95%confidence interval:0.886-1.000)in the training cohort and 0.958(0.877-1.000)in the test cohort and provided superior clinical benefit to either the clinical or radiomic models alone,as demonstrated by DCA.CONCLUSION These results indicate that the CTE-based radiomic-clinical nomogram is a promising imaging biomarker for MH and serves as a potential noninvasive alternative to enteroscopy for MH assessment in SBCD patients.

Role of Candida species in pathogenesis, immune regulation, and prognostic tools for managing ulcerative colitis and Crohn's disease

The gut microbiome plays a key role in the pathogenesis and disease activity of inflammatory bowel disease(IBD).While research has focused on the bacterial microbiome,recent studies have shifted towards host genetics and host-fungal interactions.The mycobiota is a vital component of the gastrointestinal microbial community and plays a significant role in immune regulation.Among fungi,Candida species,particularly Candida albicans(C.albicans),have been extensively studied due to their dual role as gut commensals and invasive pathogens.Recent findings indicate that various strains of C.albicans exhibit consid-erable differences in virulence factors,impacting IBD's pathophysiology.Intestinal fungal dysbiosis and antifungal mucosal immunity may be associated to IBD,especially Crohn's disease(CD).This article discusses intestinal fungal dysbiosis and antifungal immunity in healthy individuals and CD patients.It discusses factors influencing the mycobiome's role in IBD pathogenesis and highlights significant contributions from the scientific community aimed at enhancing understanding of the mycobiome and encouraging further research and targeted intervention studies on specific fungal populations.Our article also provided insights into a recent study by Wu et al in the World Journal of Gastroenterology regarding the role of the gut microbiota in the pathogenesis of CD.

Contribution of gut microbiota to the development of Crohn's disease:Insights gained from fecal microbiota transplantation studies in mice

We would like to present some new thoughts on the publication in the journalpublished in August 2024 in World Journal of Gastroenterology.We specificallyfocused on the alterations in the intestinal tract,mesenteric adipose tissue(MAT),and systemic inflammatory changes in mice following fecal flora transplantationinto a mouse model of Crohn's disease(CD).Accumulating evidence suggests thatthe occurrence of CD is influenced by environmental factors,host immune status,genetic susceptibility,and flora imbalance.One microbiota-based intervention,fecal microbiota transplantation,has emerged as a potential treatment option forCD.The MAT is considered a"second barrier"around the inflamed intestine.Theinteraction between gut microbes and inflammatory changes in MAT has attractedconsiderable interest.In the study under discussion,the authors transplantedfetal fecal microorganisms from patients with CD and clinically healthy donors,respectively,into 2,4,6-trinitrobenzene sulfonic acid-induced CD mice.Theresearch explored the complex interplay between MAT,creeping fat,inflammation,and intestinal flora in CD by evaluating intestinal and mesenteric lesions,along with the systemic inflammatory state in the mice.This article providesseveral important insights.First,the transplantation of intestinal flora holdssignificant potential as a therapeutic strategy for CD,offering hope for patientswith CD.Second,it presents a novel approach to the diagnosis and treatment ofCD:The inflammatory response in CD could potentially be assessed throughpathological or imaging changes in the MAT,and CD could be treated bytargeting the inflammation of the MAT.

Computed tomography-based radiomics combined with machine learning allows differentiation between primary intestinal lymphoma and Crohn's disease

BACKGROUND Due to similar clinical manifestations and imaging signs,differential diagnosis of primary intestinal lymphoma(PIL)and Crohn's disease(CD)is a challenge in clinical practice.AIM To investigate the ability of radiomics combined with machine learning methods to differentiate PIL from CD.METHODS We collected contrast-enhanced computed tomography(CECT)and clinical data from 120 patients form center 1.A total of 944 features were extracted singlephase images of CECT scans.Using the last absolute shrinkage and selection operator model,the best predictive radiographic features and clinical indications were screened.Data from 54 patients were collected at center 2 as an external validation set to verify the robustness of the model.The area under the receiver operating characteristic curve,accuracy,sensitivity and specificity were used for evaluation.RESULTS A total of five machine learning models were built to distinguish PIL from CD.Based on the results from the test group,most models performed well with a large area under the curve(AUC)(>0.850)and high accuracy(>0.900).The combined clinical and radiomics model(AUC=1.000,accuracy=1.000)was the best model among all models.CONCLUSION Based on machine learning,a model combining clinical data with radiologic features was constructed that can effectively differentiate PIL from CD.

Establishment of a surveillance program for anal cancer in Crohn's disease

This letter discusses the incidence of anal cancer among Crohn's disease(CD)-related malignancies.Patients with CD have been demonstrated to be at a higher risk of developing small bowel and colorectal cancers than healthy individuals.Although CD-associated anal cancer is relatively rare,patients with CD accom-panied by anal or perianal lesions are at increased risk of anal cancer.Addi-tionally,compared to ulcerative colitis,which is also an inflammatory disease,CD-related anal cancer is often detected at an advanced stage owing to the complexity of CD and is associated with a poor prognosis with frequent local recurrences.Therefore,the detection of early-stage cancer is crucial for improving the prognosis.However,the surveillance methods recommended for CD-related malignancies in the United States and Europe are similar to those for ulcerative colitis.They are not appropriate for detecting CD-related malignancies in the recto-anal region.Therefore,there is an urgent need for surveillance programs aimed at the early detection of malignant anorectal lesions in patients with CD.

Advances in the research of intestinal fungi in Crohn's disease

This article reviews of the original research published by Wu et al in the World Journal of Gastroenterology,delving into the pivotal role of the gut microbiota in the pathogenesis of Crohn's disease(CD).Insights were gained from fecal microbiota transplantation(FMT)in mouse models,revealing the intricate interplay between the gut microbiota,mesenteric adipose tissue(MAT),and creeping fat.The study uncovered the characteristics of inflammation and fibrosis in the MAT and intestinal tissues of patients with CD;moreover,through the FMT mouse model,it observed the impact of samples from healthy patients and those with CD on symptoms.The pathogenesis of CD is complex,and its etiology remains unclear;however,it is widely believed that gut microbiota dysbiosis plays a significant role.Recently,with the development and application of next-generation sequen-cing technology,research on the role of fungi in the pathogenesis and chronicity of CD has deepened.This editorial serves as a supplement to the research by Wu et al who discussed advances related to the study of fungi in CD.

Advancing perioperative optimization in Crohn's disease surgery with machine learning predictions

This editorial offers commentary on the article which aimed to forecast the likelihood of short-term major postoperative complications(Clavien-Dindo grade≥III),including anastomotic fistula,intra-abdominal sepsis,bleeding,and intestinal obstruction within 30 days,as well as prolonged hospital stays follow-ing ileocecal resection in patients with Crohn’s disease(CD).This prediction re-lied on a machine learning(ML)model trained on a cohort that integrated a no-mogram predictive model derived from logistic regression analysis and a random forest(RF)model.Both the nomogram and RF showed good performance,with the RF model demonstrating superior predictive ability.Key variables identified as potentially critical include a preoperative CD activity index≥220,low preope-rative serum albumin levels,and prolonged operation duration.Applying ML ap-proaches to predict surgical recurrence have the potential to enhance patient risk stratification and facilitate the development of preoperative optimization strate-gies,ultimately aiming to improve post-surgical outcomes.However,there is still room for improvement,particularly by the inclusion of additional relevant clinical parameters,consideration of medical therapies,and potentially integrating mole-cular biomarkers in future research efforts.

Physician-dependent diagnosis delay in Crohn's disease:A pseudoproposition or not?

The challenge of diagnosis delay in inflammatory bowel disease(IBD)has emerged as a significant concern for both patients and healthcare professionals.The widely accepted notion that there is an extended time frame from the onset of symptoms to the definitive diagnosis is often attributed to the heterogeneity of IBD and the non-specificity of clinical manifestations.Specific to patients with Crohn’s disease,the issue of delayed diagnosis appears to be more pronounced across different regions globally.The intricate interplay of real-world factors has led to debates regarding the primary contributors to these diagnostic delays.Drawing a comparison solely between patients and physicians and implicating the latter as the predominant influence factor may fall into a simplistic either-or logical trap that may obscure the truth.This letter,grounded in published evidence,explores areas for improvement in a forthcoming paper within the field,hoping to pinpoint the culprit behind the diagnosis delay issue for IBD patients rather than simply attributing it to so-called“physician-dependent factors”.Our objective is to motivate healthcare providers and policymakers in relevant fields to reflect on strategies for addressing this problem to reduce diagnostic delays and enhance patient outcomes.

Small bowel adenocarcinoma and Crohn's disease: Any further ahead than 50 years ago?

This review of the literature on small bowel carcinoma associated with Crohn's disease specifically addresses the incidence, risk factors, and protective factors which have been identified. It also reviews the clinical presentation, the current modalities of diagnosis, the pathology, treatment, and surveillance. Finally, the prognosis and future direction are addressed. Our experience with small bowel adenocarcinoma in Crohn's disease is reported. Readers will be provided with a better understanding of this rare and often poorly recognized complication of Crohn's disease.

Pediatric stricturing Crohn's disease

Crohn’s disease(CD)is a chronic inflammatory disease of the digestive tract.The incidence of pediatric CD is increasing and is currently 2.5-11.4 per 100000 world-wide.Notably,approximately 25%of children with CD develop stricturing CD(SCD)that requires intervention.Symptomatic stricturing diseases refractory to pharmacological management frequently require non-pharmacological interventions.Non-pharmacological therapeutic strategies include endoscopic balloon dilatation,stricturoplasty,and surgical resection of the strictured seg-ment.However,strictures tend to recur postoperatively regardless of treatment modality.The lifetime risk of surgery in patients with childhood SCD remains at 50%-90%.Thus,new and emerging strategies,advanced diagnostic tools,and minimally invasive approaches are under investigation to improve the outcomes and overall quality of life of pediatric patients with SCD.

Impact of different anastomosis methods on post-recurrence after intestinal resection for Crohn's disease:A meta-analysis

BACKGROUND Crohn's disease(CD)is a chronic inflammatory disease of the gastrointestinal tract,often requiring intestinal resection as a common treatment.However,recurrence after surgery is common.The anastomotic configuration after bowel resection appears to be associated with the recurrence of CD.Previous studies have suggested that the Kono-S anastomosis may help to reduce the recurrence rate.However,the results remain controversial.Therefore,evidence-based evidence is needed to prove the advantages of Kono-S anastomosis.AIM To measure the influence of anastomosis techniques on the long-term relapse rate of CD by conducting a meta-analysis.METHODS PubMed,Scopus,and Cochrane Library were searched until October 8,2023.Patients who underwent intestinal resection due to CD were included.The intervention measures included Kono-S anastomosis,whereas the control group received traditional anastomosis such as end-to-end,end-to-side,and side-to-side anastomosis.Only randomized clinical trials and observational studies were included.The primary outcome measures were hospital stay post-surgery,overall postoperative complication incidence,the proportion of Clavien-Dindo grade IIIa or higher,overall postoperative recurrence rate,and Rutgeerts score.RESULTS From 2011 to 2023,six articles met the inclusion and exclusion criteria.The results indicated that Kono-S anastomosis can reduce the hospital stay post-surgery of patients with CD[MD=-0.26,95%CI:-0.42 to-0.10,P=0.002]than other traditional anastomosis methods.Compared to other traditional anastomosis methods,Kono-S anastomosis can significantly reduce the total recurrence rate[MD=0.40,95%CI:0.17 to 0.98,P=0.05]and postoperative Rutgeerts score[MD=-0.81,95%CI:-0.96 to-0.66,P<0.001]in patients with CD.However,there is no significant disparity in the overall occurrence of postoperative complications and the proportion of Clavien-Dindo≥IIIa.CONCLUSION Kono-S anastomosis has the potential to expedite the recuperation of CD and diminish relapse hazards;however,additional larger trials are necessary to authenticate its effectiveness.

Fecal microbiota transplantation cured epilepsy in a case with Crohn's disease: The first report

Fecal microbiota transplantation(FMT)is a promising strategy that involves reconstruction of gut microbiota.Recently,it has been considered as a treatment of Crohn’s disease(CD)and certain neurological diseases.Here,to the best of our knowledge,we report the first case that used FMT to achieve remission of intestinal and neurological symptoms in a girl with CD and a 17-year history of epilepsy.During the 20 mo of follow-up,FMT has proved its efficacy in preventing relapse of seizures after withdrawing the antiepileptic drugs.Furthermore,this finding highlights the role of microbiota-gut-brain axis and inspires a novel treatment for epilepsy through remodeling gut microbiota.

Randomized controlled trial: Moxibustion and acupuncture for the treatment of Crohn's disease

AIM: To evaluate the clinical efficacy and safety of acupuncture and moxibustion for the treatment of active Crohn&#x02019;s disease (CD).

Factors affecting recurrence after surgery for Crohn's disease

Although in Crohn's disease post-operative recurrence is common, the determinants of disease recurrence remain speculative. The aim of this study was to examine factors affecting post-operative recurrence of Crohn's disease. A Medline-based literature review was carried out. The following factors were investigated: age at onset of disease, sex, family history of Crohn's disease,smoking, duration of Crohn's disease before surgery,prophylactic medical treatment (corticosteroids, 5-amino salicylic acid [5-ASA] and immunosuppressants),anatomical site of involvement, indication for surgery (perforating or non-perforating disease), length of resected bowel, anast-omotic technique, presence of granuloma in the specimen, involvement of disease at the resection margin, blood transfusions and postoperative complications. Smoking significantly increases the risk of recurrence (risk is approximately twice as high), especially in women and heavy smokers. Quitting smoking reduces the post-operative recurrence rate. A number of studies have shown a higher risk when the duration of the disease before surgery was short. There were, however, different definitions of 'short' among the studies. Prophylactic cortic-osteroids therapy is not effective in reducing the post-operative recurrence. A number of randomized controlled trials offered evidence of the efficacy of 5-ASA (mesalazine) in reducing post-operative recurrence. Recently, the thera-peutic efficacy of immunosuppressive drugs (azathioprine and 6-mercaptopurine) in the prevention of post-operative recurrence has been investigated and several studies have reported that these drugs might help prevent the recurrence. Further clinical trials would be necessary to evaluate the prophylactic efficacy of immunosuppressants.Several studies showed a higher recurrence rate in patients with perforating disease than in those with non-perforating disease. However, evidence for differing recurrence rates in perforating and non-perforating diseases is inconclusive.A number of retrospective studies reported that a stapled functional end-to-end anastomosis was associated with a lower recurrence rate compared with other types of anastomosis. However, prospective randomized studies would be necessary to draw a definite conclusion. Many studies found no difference in the recurrence rates between patients with radical resection and non-radical resection. Therefore, minimal surgery including strictureplasty has been justified in the management of Crohn's disease. In this review, the following factors do not seem to be predictive of post-operative recurrence:age at onset of disease, sex, family history of Crohn's disease, anatomical site of disease, length of resected bowel, presence of granuloma in the specimen, blood transfusions and post-operative complications. The most significant factor affecting post-operative recurrence of Crohn's disease is smoking. Smoking significantly increases the risk of recurrence. A short disease duration before surgery seems, albeit to a very minor degree, to be associated with a higher recurrence rate. 5-ASA has been shown with some degree of confidence to lead to a lower recurrence rate. The prophylactic efficacy of immunosuppressive drugs should be assessed in future.A wider anastomotic technique after resection may reduce the post-operative recurrence rate, though this should be investigated with prospective randomized controlled trials.

Toll-like receptor 4 and NOD2/CARD15 mutations in Hungarian patients with Crohn's disease: Phenotype-genotype correlations

AIM: To determine common NOD2/CARD15 mutations and TLR4 D299G polymorphism in Hungarian patients with CD. METHODS: A total of 527 unrelated patients with CD (male/female: 265/262, age: 37.1 (SD 7.6) years) and 200 healthy subjects were included. DNA was screened for possible NOD2/CARD15 mutations by denaturing high-performance liquid chromatography (confirmed by direct sequencing). TLR4 D299G was tested by PCR-RFLP. RESULTS: NOD2/CARD15 mutations were found in 185 patients (35.1%) and in 33 controls (16.5%,P<0.0001). SNP8/R702W (10.8% vs 6%, P= 0.02), SNP13/3020insC (19.4% vs 5%, P<0.0001) and exon4 R703C (2.1% vs 0%, P= 0.02) mutations were more frequent in CD, while the frequency of SNP12/G908R was not increased. The frequency of TLR4 D299G was not different (CD: 9.9% vs controls: 12.0%). Variant NOD2/CARD15 allele was associated with an increased risk for CD (ORhet=1.71, 95%CI=1.12-2.6, P= 0.0001, ORtwo-risk alleles = 25.2, 95%CI =4.37- ,P<0.0001), early disease onset (carrier: 26.4 years vs non-carrier: 29.8 years, P=0.0006), ileal disease (81.9% (?) 69.5%, OR = 1.99, 95%CI = 1.29-3.08, P= 0.02, presence of NOD2/CARD15 and TLR4: 86.7% vs 64.8%), stricturing behavior (OR = 1.69,95%CI = 1.13-2.55, P= 0.026) and increased need for resection (OR=1.71, 95%CI: 1.13-2.62, P= 0.01), but not with duration, extra-intestinal manifestations, familial disease or smoking. TLR4 exhibited a modifier effect: age of onset in wt/TLR4 D299G carriers: 27.4 years vs NOD2mut/TLR D299G: 23 years (P = 0.06), in NOD2mut/wt: 26.7 years. CONCLUSION: These results confirm that variant NOD2/ CARD15 (R702W, R703C and 3020insC) alleles are associated with earlier disease onset, ileal disease, stricturing disease behavior in Hungarian CD patients. In contrast, although the frequency of TLR4 D299G polymorphism was not different from controls, NOD2/TLR4 mutation carriers tended to present at earlier age.

Circulating miR-125a but not miR-125b is decreased in active disease status and negatively correlates with disease severity as well as inflammatory cytokines in patients with Crohn's disease

AIM To determine the association of circulating mi R-125 a/b expression with the risk and disease severity of Crohn's disease(CD), and with inflammatory cytokines.METHODS Plasma samples were collected from patients with active CD(A-CD), or CD in remission(R-CD) and from healthy controls(HCs). The levels of the inflammatory cytokines interleukin-17(IL-17), tumour necrosis factor-α(TNF-α), and interferon-γ(IFN-γ) were measured by enzyme-linked immunosorbent assay. The expression of mi R-125 a/b was assessed by quantitative polymerase chain reaction(q PCR).RESULTS Twenty-nine A-CD patients, 37 R-CD patients, and 37 HCs were included in the study. Plasma mi R-125 a expression was decreased in A-CD patients comparedwith that in R-CD patients(P < 0.001) and HCs(P < 0.001). mi R-125 a expression levels enabled the differentiation of A-CD from R-CD patients [area under curve(AUC) = 0.854] and from HCs(AUC = 0.780), whereas mi R-125 b expression did not. mi R-125 a was negatively correlated with C-reaction protein(CRP)(P = 0.017), erythrocyte sedimentation rate(ESR)(P = 0.026), Crohn's disease activity index(CDAI)(P = 0.003), IL-17(P = 0.015), and TNF-α(P = 0.004) in A-CD patients. Furthermore, mi R-125 a was negatively associated with CRP(P = 0.038) and CDAI(P = 0.021) in R-CD patients. Regarding mi R-125 b, no association with CRP, CDAI, IL-17, TNF-α, or IFN-γ was found in A-CD or in R-CD patients. mi R-125 a levels gradually increased in A-CD patients who achieved clinical remission(P = 0.009) after 3-mo treatment, whereas they remained unchanged among patients who failed to achieve remission. No changes in mi R-125 b expression were detected in remission or non-remission patients after treatment. CONCLUSION Circulating mi R-125 a but not mi R-125 b is decreased in patients with active disease status and negatively correlates with disease severity and inflammatory cytokines in patients with CD.

Mycobacterium avium subspecies paratuberculosis causes Crohn's disease in some inflammatory bowel disease patients

Crohn’s disease(CD)is a chronic inflammatory condition that plagues millions all over the world.This debilitating bowel disease can start in early childhood and continue into late adulthood.Signs and symptoms are usually many and multiple tests are often required for the diagnosis and confirmation of this disease.However,little is still understood about the cause(s)of CD.As a result,several theories have been proposed over the years.One theory in particular is that Mycobacterium avium subspecies paratuberculosis(MAP)is intimately linked to the etiology of CD.This fastidious bacterium also known to cause Johne’s disease in cattle has infected the intestines of animals for years.It is believed that due to the thick,waxy cell wall of MAP it is able to survive the process of pasteurization as well as chemical processes seen in irrigation purification systems.Subsequently meat,dairy products and water serve as key vehicles in the transmission of MAP infection to humans(from farm to fork)who have a genetic predisposition,thus leading to the development of CD.The challenges faced in culturing this bacterium from CD are many.Examples include its extreme slow growth,lack of cell wall,low abundance,and its mycobactin dependency.In this review article,data from 60 studies showing the detection and isolation of MAP by PCR and culture techniques have been reviewed.Although this review may not be 100%comprehensive of all studies,clearly the majority of the studies overwhelmingly and definitively support the role of MAP in at least30%-50%of CD patients.It is very possible that lack of detection of MAP from some CD patients may be due to the absence of MAP role in these patients.The latter statement is conditional on utilization of methodology appropriate for detection of human MAP strains.Ultimately,stratification of CD and inflammatory bowel disease patients for the presence or absence of MAP is necessary for appropriate and effective treatment which may lead to a cure.

Ephrin-B2 is differentially expressed in the intestinal epithelium in Crohn's disease and contributes to accelerated epithelial wound healing in vitro

AIM:Eph receptor tyrosine kinases and their membrane bound receptor-like ligands, the ephrins, represent a bi-directional cell-cell contact signaling system that directs epithelial movements in development. The meaning of this system in the adult human gut is unknown. We investigated the Eph/ephrin mRNA expression in the intestinal epithelium of healthy controls and patients with inflammatory bowel disease (IBD). METHODS: mRNA expression profiles of all Eph/ephrin family members in normal small intestine and colon were established by real-time RT-PCR. In addition, differential expression in IBD was investigated by cDNA array technology, and validated by both real-time RT-PCR and immunohistochemistry. Potential effects of enhanced EphB/ephrin-B signaling were analyzed in an in vitro IEC-6 cell scratch wound model. RESULTS: Human adult intestinal mucosa exhibits a complex pattern of Eph receptors and ephrins. Beside the known prominent co-expression of EphA2 and ephrinAl, we found abundantly co-expressed EphB2 and ephrin-B1/2. Interestingly, cDNA array data, validated by real-time PCR and immunohistochemistry, showed upregulation of ephrin-B2 in both perilesional and lesional intestinal epithelial cells of IBD patients, suggesting a role in epithelial homeostasis. Stimulation of ephrin-B signaling in ephrin- B1/2 expressing rat IEC-6-cells with recombinant EphB1-Fc resulted in a significant dose-dependent acceleration of wound closure. Furthermore, fluorescence microscopy showed that EphB1-Fc induced coordinated migration of wound edge cells is associated with enhanced formation of lamellipodial protrusions into the wound, increased actin stress fiber assembly and production of laminin at the wound edge. CONCLUSION: EphB/ephrin-B signaling might represent a novel protective mechanism that promotes intestinal epithelial wound healing, with potential impact on epithelial restitution in IBD.

Treatment of peri-anal fistula in Crohn's disease

Anal fistulas are a common manifestation of Crohn's disease(CD). The first manifestation of the disease is often in the peri-anal region, which can occur years before a diagnosis, particularly in CD affecting the colon and rectum. The treatment of peri-anal fistulas is difficult and always multidisciplinary. The European guidelines recommend combined surgical and medical treatment with biologic drugs to achieve best results. Several different surgical techniques are currently em-ployed. However, at the moment, none of these tech-niques appear superior to the others in terms of healing rate. Surgery is always indicated to treat symptomatic, simple, low intersphincteric fistulas refractory to medi-cal therapy and those causing disabling symptoms. Ut-most attention should be paid to correcting the balance between eradication of the fistula and the preservationof fecal continence.