OBJECTIVES:Exclusive enteral nutrition (EEN) is a well-established therapy for inducing remission in luminal Crohn's disease (CD), but its role in biologic-refractory patients remains unclear. This study aimed to evaluate the efficacy of EEN in biologic-refractory CD in adults and identify factors influencing treatment outcomes. METHODS:A single-center retrospective study was conducted on adult CD patients who received EEN between January 2021 and December 2024. Patients with active disease despite prior biologic therapy were included, along with a biologic-naïve subgroup for comparison. Clinical and laboratory data were analyzed, and remission rates were compared, stratified by the number of failed biologics. Logistic regression identified predictors of EEN efficacy. RESULTS:Among 224 patients, 94 were biologics-refractory, and 130 were biologics-naïve. Clinical remission at week 6 was achieved in 63.8% of biologic-refractory versus 73.8% of biologic-naïve patients (P = 0.11). Remission rates in patients failing one or two biologics were similar to biologic-naïve patients, but were significantly lower in those failing more than three biologics (P < 0.01). Multivariate analysis identified gastrointestinal bleeding (OR = 0.08; 95% [CI] = [0.03-1.20], P = 0.03) and failure of more than three biologics (OR = 0.11; 95% [CI] = [0.02-0.50], P < 0.01) as independent risk factors for nonremission. CONCLUSIONS:EEN is an effective salvage therapy for biologic-refractory CD in adults, but its efficacy diminishes with increased biologic failures. Additionally, active CD with gastrointestinal bleeding is associated with a lower likelihood of achieving clinical remission.

PURPOSE:Anastomotic recurrence after ileocolectomy for Crohn's disease may be related to the gut microbiota, but the role of mycobiota remains unclear. This study aimed to investigate associations between mucosal mycobiota at resection and early postoperative endoscopic recurrence, and assess their predictive potential. METHODS:We recruited 55 Crohn's disease patients undergoing bowel resection (October 2022-February 2024) with one-year endoscopic follow-up. Mucosal samples obtained during surgery underwent fungal internal transcribed spacer 1 sequencing to characterize the fungal communities. Multivariate analysis identified risk factors for early postoperative endoscopic recurrence. Predictive model performance was evaluated using receiver operating characteristic curve analysis. RESULTS:Twenty patients (36.4%) developed early postoperative endoscopic recurrence and were assigned to the recurrence group. Multivariate analysis identified preoperative low serum albumin level and elevated postoperative neutrophil-to-lymphocyte ratio as independent risk factors. The recurrence group exhibited an increased relative abundance of Basidiomycota, an elevated Basidiomycota/Ascomycota ratio, and heightened relative abundances of Malassezia restricta and Debaryomyces hansenii. A combined predictive model integrating three potential fungal biomarkers demonstrated superior predictive performance for early postoperative endoscopic recurrence. CONCLUSION:Early postoperative endoscopic recurrence in Crohn's disease is significantly associated with mucosal fungal dysbiosis during bowel resection. Integrating mycobial factors can more effectively predict early postoperative endoscopic recurrence.

Oral probiotics hold therapeutic potential for ulcerative colitis (UC), but their low bioavailability greatly limits clinical efficacy. Here, we designed a montmorillonite-Lactobacillus acidophilus biofilm (MLB) delivery strategy to enhance probiotic stability, intestinal adhesion, and therapeutic efficiency. MLB was prepared by inducing the clinically common strain Lactobacillus acidophilus to form biofilms on montmorillonite, an antidiarrheal agent widely used in clinics. The in vitro assays demonstrated that montmorillonite significantly promoted biofilm formation, thereby improving bacterial survival in gastrointestinal conditions and enhancing mucosal adhesion. In vivo, MLB showed superior efficacy in alleviating DSS-induced colitis compared with free bacteria or non-biofilm mixtures. Mechanistically, MLB remodeled gut microbiota composition and restored microbial bile acid metabolism through elevated bile salt hydrolase activity. This led to increased production of secondary bile acids, which in turn promoted anti-inflammatory macrophage polarization and facilitated inflammation resolution. Together, these findings demonstrate that MLB enhances the efficacy of oral probiotics by targeting the microbiota-bile acid-immune axis, representing a safe and practical approach for UC treatment.

Background: Crohn’s disease (CD) has an evolving course and may progress to stricturing or penetrating complications, intestinal surgery, and treatment escalation. Existing models often rely on baseline or time-agnostic data, limiting risk assessment during routine follow-up. We developed and externally validated a time-updated model CD-ProFormer for prediction of CD progression using longitudinal electronic health records (EHRs). Methods: We assembled multicenter EHR cohorts: a development cohort from Peking Union Medical College Hospital (PUMCH) (761 patients; 11,984 visits) and external validation cohorts from Guizhou (74 patients; 510 visits) and Nanjing (271 patients; 3934 visits). Using each visit as index, CD-ProFormer, a time-aware Transformer that used EHR trajectories to predict 1-, 3-, and 5-year risks of behavior progression, CD-related intestinal surgery, and major medication initiation. Global SHAP, temporal SHAP, decision curve analysis, and representative cases assessed interpretability and clinical utility. Findings: CD-ProFormer showed strong internal discrimination for behavior progression, with AUROCs of 0.979, 0.951, and 0.910 at 1, 3, and 5 years; macro-area under the curve for first-progression time-window classification was 0.811. External validation remained acceptable, with AUROCs of 0.725–0.879 in Guizhou and 0.856–0.913 in Nanjing, consistently exceeding recurrent baselines. Performance for surgery and medication initiation was comparable to recurrent models and better than conventional models. Interpretation: In this prognostic study, CD-ProFormer enabled time-updated, horizon-specific prediction of CD behavior progression, with surgery and medication initiation assessed in parallel. These findings suggest that prognosis in CD can be updated at follow-up visits using routinely collected longitudinal data and may support risk stratification, monitoring intensity, and timely treatment planning.

BACKGROUND:Isolated small bowel Crohn's disease (ISBCD) is often associated with poorer clinical outcomes. This study aims to summarize the clinical characteristics of patients with ISBCD and to investigate the risk factors for surgical recurrence due to disease recurrence. METHODS:A retrospective study was conducted using a prospective database of Crohn's patients. Patients with ISBCD were screened and divided into stricturing and nonstricturing groups according to the Montreal classification behavior definition. The primary endpoint was reoperation due to postoperative recurrence of Crohn's disease. Other endpoints included intraoperative and postoperative outcomes, as well as clinical characteristics. Multivariable Cox regression analysis was used to assess the independent risk factors for surgical recurrence. RESULTS:From January 2017 to June 2024, totally 234 patients (135 in the stricturing group) were included. After propensity score matching, with 79 patients in each group. During the follow-up period (1-90 months), surgical recurrence rates were significantly higher in the stricturing group (11%) compared to the nonstricturing group (4%) (P = 0.04), this was confirmed in Kaplan-Meier curve with log-rank analysis (P = 0.04). No significant differences were observed in postoperative outcomes between the two groups. Variables with P < 0.1 in univariable analysis (stricturing behavior, smoking history, hypoalbuminemia, escalation, or conversion of biologic during follow-up) were incorporated into the multivariable Cox regression analysis, which demonstrated the stricturing behavior [hazard ratio (HR) 4.010; 95% confidence interval (CI) 1.024-15.704; P = 0.04] and the escalation or conversion of biologic agents (HR 6.453; 95% CI 1.906-21.844; P < 0.01) postoperatively were independent risk factors for surgical recurrence. CONCLUSION:The stricturing phenotype is associate with increased risk of operative surgical recurrence in patients with ISBCD. These patients should have a more active prophylactic strategy for the prevention of recurrence after surgery.

Conventional targeted therapies for inflammatory bowel disease (IBD) often rely on unstable biological recognition elements. While molecularly imprinted polymers (MIP) offer robust synthetic alternatives, their utility is limited by an "always-on" binding state: even weak non-specific adsorption can significantly compromise their target-binding capacity. We convert static MIP into reactive oxygen species (ROS)-activated therapeutic actuators by conjugating mannose to transferrin-imprinted MIP via a ROS-cleavable linker. The saccharide acts dually as a therapeutic agent and a protective cloak. It sterically blocks non-specific binding during intestinal transit. At inflammatory sites, elevated ROS levels (higher than in healthy tissue) trigger simultaneous mannose release and activation of high-affinity targeting. This enables precise MIP anchoring to the inflamed epithelium for physical barrier formation and localized microbiome modulation. In murine colitis models, this achieved mucosal healing, mitigated inflammation, and microbiota rebalancing using a mannose equivalent dose of 27.2 mg/kg/d, benchmarking against free mannose and non-responsive MIP controls. This work establishes a generalizable paradigm for targeted recognition and drug delivery in complex physiological environments, paving the way for intelligent, disease-responsive nanomedicines.

BACKGROUND:The impact of anastomotic leak (AL) on long-term outcomes following resection for colorectal cancer (CRC) remains a subject of ongoing debate. Recent studies investigating this topic have reported discrepant findings. MATERIALS:Studies investigating the impact of AL on long-term oncological outcomes after CRC resection were identified from the electronic databases to perform meta-analysis. Meta-regression and subgroup analysis were performed to identify and adjust for confounders. RESULTS:A total of 56 studies were enrolled. Meta-analysis showed that AL was associated with an increased local recurrence (LR) in rectal cancer (HR = 2.06, 95% CI: 1.53-2.76, p < 0.001) but not colonic cancer (HR = 1.68, 95% CI: 0.62-4.53, p = 0.309). In contrast, AL was associated with an increased distant recurrence (DR) in colonic cancer (HR = 1.43, 95% CI 1.15-1.78, p = 0.001), but not rectal cancer (HR = 1.07, 95% CI: 0.82-1.39, p = 0.639). AL was associated with worse overall survival (OS) in both rectal (HR = 1.44, 95% CI: 1.23-1.68, p < 0.001) and colonic cancer (HR = 1.67, 95% CI: 1.33-2.09, p < 0.001), as well as lower cancer-specific survival (CSS) in rectal cancer (HR = 1.51, 95% CI: 1.10-2.08, p = 0.011). Additionally, AL was linked to decreased disease-free survival (DFS) in both rectal (HR = 1.56, 95% CI: 1.23-1.98, p < 0.001) and colonic cancer (HR = 1.66, 95% CI: 1.21-2.26, p = 0.002). CONCLUSION:AL has distinct impacts on recurrence patterns in colonic and rectal cancer, and is consistently linked to reduced long-term survival outcomes. These adverse effects may be attributable to interruption or delay of adjuvant therapy following AL.

BACKGROUND:Handsewn Kono-S anastomosis is safe and associated with a reduction in postoperative recurrence (POR) in Crohn disease (CD). This study aimed to investigate the advantages of stapled Kono-S anastomosis in patients with CD who underwent intestinal anastomosis. METHODS:Patients with CD who underwent intestinal anastomosis were reviewed via a prospectively maintained database. Patients who underwent conventional stapled side-to-side anastomosis were classified into the conventional group, and those who underwent stapled Kono-S anastomosis were classified into the Kono-S group. The primary endpoint was modified endoscopic recurrence (mER; ≥i2b). Other endpoints were endoscopic recurrence (ER; ≥i2); severe ER (i3 and i4); intra- and postoperative outcomes, including morbidity and hospital stay; and cross-sectional parameters. Multivariate logistic regression analysis was performed to assess the independent risk factors for mER. RESULTS:Between 2020 and 2023, 199 patients (63 in the Kono-S group) were included in this study. After matching the 63 patients in each group, the overall rates of mER, ER, and severe ER were 19.0%, 24.6%, and 8.7%, respectively. The mER, ER, and severe ER rates were lower in the Kono-S group than in the conventional group (12.7% vs 25.4% [P =.07], 20.6% vs 28.6% [P =.30], and 6.3% vs 11.1% [P =.34], respectively). Multivariate analysis indicated that stapled Kono-S anastomosis (odds ratio [OR], 0.35; 95% CI, 0.12-0.98; P =.047) was an independent protective factor for mER, whereas male gender (OR, 7.75; 95% CI, 1.50-40.00; P =.01) and BMI of <18.5 kg/m2 (OR, 3.27; 95% CI, 1.11-9.67; P =.03) were independent risk factors for mER. CONCLUSION:Stapled Kono-S anastomosis is safe for patients with CD. However, stapled Kono-S anastomosis may not be a protective factor against POR compared with conventional stapled side-to-side anastomosis.

INTRODUCTION:Anastomotic ulcers are common after ileocolonic resection in patients with Crohn's disease (CD). However, the endoscopic prognosis of isolated anastomotic lesions after treatment adjustment remains unclear. METHODS:We retrospectively included CD patients with anastomotic lesions who were referred to our center for ileocolonoscopy between 2020 and 2024. We conducted an initial evaluation of the impact of treatment adjustment on the endoscopic prognosis of anastomotic lesions. In addition, we analyzed the association between different adjustment strategies and endoscopic outcome. RESULTS:In total, 199 eligible CD patients with anastomotic lesions were included in our study. Treatment adjustment promoted mucosal healing (multivariable Cox hazard ratio [HR]: 2.376, 1.400-4.032, P = 0.001) and endoscopic improvement (multivariable Cox HR: 2.373, 1.596-3.530, P < 0.001). We also found that the endoscopic ulcer improvement of biologics to biologics switching was superior to that of nontreatment adjustment (Cox HR: 2.055, 1.212-3.482, P = 0.007). Cox regression analyses further confirmed that nonbiologics to biologics switching was associated with better endoscopic mucosal healing (Cox HR: 2.751, 1.494-5.063, P = 0.001) and ulcer improvement (Cox HR: 2.154, 1.322-3.509, P = 0.002). Regarding patients with insufficient trough levels of biologics, biologic optimization significantly improved endoscopic mucosal healing (Cox HR: 2.854, 1.345-6.053, P = 0.006) and endoscopic ulcer improvement (Cox HR: 2.344, 1.288-4.265, P = 0.005). DISCUSSION:Treatment adjustment contributed to the improvement of endoscopic prognosis in anastomotic lesions patients. Different adjustment strategies (biologics to biologics switching, nonbiologics to biologics switching, biologic optimization) similarly resulted in better endoscopic outcome.

To the Editor: Patients with Crohn's disease (CD) often undergo bowel resection due to complications. Indeed, bowel resection is not a curative approach and has relatively high rates of postoperative complications and recurrence.[1] The 10-year risk of having a second resection after the first is 35%, although more recent studies suggest that this may have decreased to closer to 30%.[2] How to prevent postoperative recurrence (POR) has become a major concern. Studies have shown that mesalazine and azathioprine do not effectively prevent POR and biologics have a better preventive effect. The relative efficacies of different biologics remain controversial, suggesting that further trials are needed. This study aimed to evaluate the effectiveness of prophylactic therapy in preventing POR after intestinal surgery in patients with CD in a real-world setting and to compare vedolizumab, ustekinumab, and infliximab for effectiveness, which is currently a gap in China. This study retrospectively analyzed patients with CD treated at Jinling Hospital, Medical School of Nanjing University, from March 2021 to August 2023. Inclusion criteria were: (1) Meeting the diagnostic criteria for CD in the 2023 Chinese national clinical practice guideline on diagnosis and management of Crohn's disease;[1] (2) Undergoing intestinal surgery, including partial resection of the intestine, colon, and rectum; intestinal perforation repair surgery; stoma, etc.; (3) Undergoing biologics treatment according to the recommended dosage and modality within 6 months after surgery for at least 3 months. Exclusion criteria were: (1) Treatment limited to simple anal fistula surgery, appendectomy, or endoscopic dilatation; (2) missed visits or lack of clinical data. Ethical approval (No. 2022DZKY-048-02) and informed consent were obtained. The baseline clinical data were collected through the hospital's electronic medical record system. The primary outcome was clinical recurrence at the end of follow-up. Disease severity was assessed clinically by the Crohn's Disease Activity Index (CDAI), which defines clinical recurrence as a CDAI >150 and a CDAI increase of 100.[1] When a case relapsed, the treatment plan was changed according to the specific situation, including reoperation, switching to another biologic, co-administering immunosuppressants or hormones, re-induction, etc. The secondary outcome was the status of endoscopy recurrence. Endoscopic POR was considered with a Rutgeerts score ≥i2, and endoscopic remission with a Rutgeerts score 100 cm), esophagogastroduodenal lesions, young age at onset, and the need for steroid therapy at the initial disease onset.[1] In the present study, of the five examined risk factors, patients were more likely to have POR only with extensive lesions. In addition, cases requiring immunosuppressant therapy throughout the course of the disease were more likely to recur. The timing of immunosuppressant administration may be a relevant factor, and more severe or poorly controlled disease may require the use of immunosuppressants. This study analyzed the actual postoperative use of biologics in patients with CD, providing data for the efficacy of different biologics in the prevention of POR in China. The current study provided certain guidance and might be used as a reference for further clinical promotion and application. Since the definitions of clinical POR and Rutgeerts score have never been formally unified, all current diagnostic modalities had limitations.[5] Our findings get only a preliminary conclusion due to the lack of a control group treated with traditional medication. As this was an observational, non-interventional study, data on endoscopy were only available if it is deemed necessary by the patients' physician. Therefore, some of the endoscopic POR data are missing and the results may be affected by inconsistent evaluation time. In conclusion, this study demonstrated that biologics (vedolizumab, ustekinumab, and infliximab) could effectively prevent POR. Ustekinumab might show a better preventive efficacy than infliximab. Patients administered immunosuppressants or with extensive lesions are more likely to undergo clinical POR.

BACKGROUND:Ulcerative colitis (UC) patients undergoing ileal pouch anal anastomosis (IPAA) will potentially have abnormal pouch function, which seriously affects their quality of life. It is usually attributed to postoperative pouch structural complications. However, symptoms of poor pouch function also occur in patients with "normal pouch". Few objective tools have been used to evaluate the pouch function with non-optimal pouch physiology. AIM:To investigate the validity of dynamic magnetic resonance defecography (DMRD) and its relationship with pouch function in UC patients undergoing IPAA. METHODS:UC patients who had IPAA surgery were recruited. Patients with structural complications were excluded. Patients were assessed by questionnaires for pouch function including ileal pouch syndrome severity (IPSS) score. DMRD was performed at resting, raising, and defecation phase. The correlation between DMRD data and pouch function was investigated. Poor pouch function was defined as IPSS score >15. RESULTS:A total of 33 patients were included. The results showed that distance from anastomosis to pubococcygeal line (PCL) at rest phase was an independent risk factor for poor pouch function ([OR] 5.65, 95 % CI 1.02-31.16, P = 0.047). The length of cuff at raising phase was an independent risk factor for urgency ([OR] 12.55, 95 % CI 1.06-148.32, P = 0.045). In addition, M-line length-a reference for assessing pelvic floor descent (normal ≤2 cm)-during defecation was an independent risk factor for incomplete defecation ([OR] 2.47, 95 % CI 1.11-5.47, P = 0.027), while M-line length at rest was an independent risk factor for stool leakage ([OR] 10.16, 95 % CI 1.15-90.07, P = 0.037). CONCLUSIONS:Magnetic resonance defecography is a potentially useful imaging modality for evaluating pouch function. Our study presented a series of DMRD parameters for functional assessment and their association with defecation disorders during dynamic monitoring. Therefore, DMRD provides information, in addition to clinical parameters, in symptomatic pouch patients.

Although mechanical tension from luminal distension is a primary regulator of gut motility, we reveal a parallel chemosensory pathway wherein long-chain unsaturated free fatty acids (LUFFAs) from dietary or enterobacterial sources directly modulate gastrointestinal motor function. Using ex vivo and in vivo contractility assays in human and murine intestinal tissues, we found that LUFFAs, particularly Omega-3 fatty acids, suppressed spontaneous contractions and delayed intestinal transit in a double bond-dependent manner. Mechanistically, selective activation of free fatty acid receptor 1/4 (FFAR1/4) on nitrergic myenteric ganglia triggered a rise in intracellular calcium and nitric oxide release, inducing smooth muscle relaxation independent of epithelial signaling. Genetic ablation of Ffar4 in enteric neurons or defect in enteric nitrergic ganglia abolished LUFFAs-mediated motility suppression and ameliorated colonic dysmotility induced by pathologically elevated LUFFAs levels. Our findings establish nitrergic ganglia as critical chemosensors translating dietary or enterobacterial lipid signals into gut motor responses.

Ulcerative colitis (UC) is a severe inflammatory bowel disease affecting millions of people worldwide, but the factors driving the condition are poorly understood. In tissue samples from individuals with UC, we found that macrophages were depleted from areas of the colon that did not yet exhibit overt epithelial inflammation. We hypothesized that toxins produced by bacteria could impair macrophages and that this could promote wider inflammation. We isolated a variant of Aeromonas genus from stool samples from UC patients, which we termed macrophage-toxic bacteria (MTB), because aerolysin secreted by MTB caused macrophage death. MTB colonized mice under pathogenic conditions and triggered colitis. Antibodies against aerolysin alleviated colitis induced by Aeromonas in mice. In a cohort, UC patients more frequently tested positive for Aeromonas than healthy controls did.

BACKGROUND:Sarcopenic obesity is associated with poor prognosis in many diseases, but its role in postoperative complications in IBD remains unclear. OBJECTIVE:To investigate the association of sarcopenic obesity with major complication risk in patients with IBD who underwent bowel resection surgery. DESIGN:Retrospective cohort analysis. SETTINGS:Single tertiary care center. PATIENTS:Patients with IBD who underwent abdominal surgery between January 2019 and December 2023 were included. Skeletal muscle mass and visceral adipose tissue were evaluated by preoperative CT at the level of the third lumbar vertebra (L3) to define sarcopenia and obesity. Patients were classified into 1 of 4 body composition groups according to the presence or absence of sarcopenia and obesity. MAIN OUTCOME MEASURES:Major postoperative complications within 30 days. RESULTS:A total of 274 patients were included. Body composition was classified as sarcopenic nonobesity in 121 patients (44.2%), nonsarcopenic nonobesity in 85 patients (31.0%), nonsarcopenic obesity in 34 patients (12.4%), and sarcopenic obesity in 34 patients (12.4%). A similar percentage of minor complications occurred in the 4 groups. However, patients with sarcopenic obesity had a significantly greater rate of major complications (52.9%) than those with nonsarcopenic obesity (28.1%), sarcopenic nonobesity (20.6%), and nonsarcopenic nonobesity (8.2%, p < 0.001). Multivariate analysis identified sarcopenic obesity as a significant risk factor for major complications (OR 14.10; 95% CI, 3.02-65.8; p < 0.001) in patients with IBD undergoing bowel resection surgery. In addition, current smokers, a change in the level of C-reactive protein (postoperative day 5 - postoperative day 1) >0 mg/L, preoperative enteral nutrition therapy, and a preoperative albumin level >35 g/L were also confirmed as independent risk factors for major complications. Moreover, nomogram models were constructed for patients with Crohn's disease and patients with ulcerative colitis to better predict the risk of major complications. LIMITATIONS:This was a single-center retrospective study. CONCLUSIONS:Sarcopenic obesity was identified as a significant risk factor for major complications in patients with IBD undergoing bowel resection surgery. See Video Abstract . IMPACTO DE LA OBESIDAD SARCOPNICA EN LOS RESULTADOS POSOPERATORIOS DE PACIENTES CON ENFERMEDAD INFLAMATORIA INTESTINAL SOMETIDOS A CIRUGA DE RESECCIN INTESTINAL UN ESTUDIO DE COHORTE RETROSPECTIVO:ANTECEDENTES:La obesidad sarcopénica se asocia con un mal pronóstico en muchas enfermedades, pero su papel en las complicaciones posoperatorias en la EII sigue sin estar claro.OBJETIVO:Investigar la asociación de la obesidad sarcopénica con el riesgo de complicaciones graves en pacientes con EII sometidos a cirugía de resección intestinal.DISEÑO:Análisis retrospectivo de cohortes de pacientes con EII sometidos a cirugía abdominal entre enero de 2019 y diciembre de 2023.ENTORNO:Centro único de atención terciaria.PACIENTES:Se evaluó la masa muscular esquelética y el tejido adiposo visceral mediante tomografía computarizada preoperatoria a la altura de la tercera vértebra lumbar (L3) para definir la sarcopenia y la obesidad. Los pacientes se clasificaron en uno de cuatro grupos de composición corporal según la presencia o ausencia de sarcopenia y obesidad.PRINCIPALES MEDIDAS DE RESULTADO:Complicaciones postoperatorias graves en 30 días.RESULTADOS:La composición corporal se clasificó como sarcopénica-no obesa en 121 pacientes (44,2 %), no sarcopénica-no obesa en 85 pacientes (31,0 %), no sarcopénica-obesa en 34 pacientes (12,4 %) y sarcopénica-obesa en 34 pacientes (12,4 %). Se produjo un porcentaje similar de complicaciones menores en los 4 grupos. Sin embargo, los pacientes con obesidad sarcopénica tuvieron una tasa significativamente mayor de complicaciones graves (52,9 %) que los pacientes con obesidad no sarcopénica (28,1 %), sarcopenia sin obesidad (20,6 %) y no sarcopenia sin obesidad (8,2 %, p < 0,001). El análisis multivariante identificó la obesidad sarcopénica como un factor de riesgo significativo de complicaciones graves (OR, 14,10; IC del 95 %: 3,02-65,8, p < 0,001) en pacientes con EII sometidos a cirugía de resección intestinal. Además, se confirmó que ser fumador actual, tener una △CRP (día 5 postoperatorio - día 1 postoperatorio) >0 mg/L, recibir terapia de nutrición enteral preoperatoria y tener un Alb >35 g/L preoperatorio también eran factores independientes de complicaciones graves. Además, se construyeron modelos nomográficos para pacientes con EC y CU, respectivamente, con el fin de predecir mejor el riesgo de complicaciones graves.LIMITACIONES:Se trata de un estudio retrospectivo realizado en un único centro.CONCLUSIONES:Se identificó la obesidad sarcopénica como un factor de riesgo significativo de complicaciones graves en pacientes con EII sometidos a cirugía de resección intestinal. ( AI-generated translation ).

ZAKα-driven ribotoxic stress response (RSR) has been shown to trigger diverse biological effects. Nevertheless, its role in the pathogenesis of ulcerative colitis (UC) remained unclear. This study aimed to determine the role of ZAKα in the development of UC. Our study found that ZAKα expression was significantly increased in colonic epithelium of UC patients and DSS-colitis mouse models. Moreover, the expression level of ZAKα mRNA showed a positive correlation with disease activity. In the colitis model, Vemurafenib, the ZAKα inhibitor, treatment reduced colonic inflammation and ameliorated intestinal mucosal barrier damage, while Anisomycin, the RSR agonist, showed the opposite effect. In vitro experiments demonstrated that Anisomycin induced pyroptosis instead of apoptosis in C26 cell line. Western blot analysis revealed that Anisomycin triggered pyroptosis via the Caspase-11/GSDMD pathway. Further animal studies confirmed that Vemurafenib downregulated this pathway, reducing colonic epithelial cell pyroptosis. Finally, blocking Caspase-11 reduced severity of DSS-induced colitis in Anisomycin-treated mice. In all, ZAKα seems to play a crucial role in the pathogenesis of colitis, as it promotes pyroptosis in colonic epithelial cells and exacerbates colitis in part by upregulating the Caspase-11/GSDMD axis. ZAKα, the key kinase driving the ribotoxic stress response (RSR), is highly expressed in colonic epithelium of UC patients, and the activation of ZAKα can upregulate the Caspase-11/GSDMD pathway to induce pyroptosis in colonic epithelial cells.

Small intestine-rectal fistulas are a rare and complex complication in Crohn’s disease, posing significant diagnostic and management challenges. This study aims to investigate their distinctive features and evaluates surgical outcomes. We conducted a retrospective analysis of Crohn’s disease patients with small intestine-rectal fistulas who underwent surgery from January 2019 to March 2023. Data on disease characteristics, postoperative quality of life, and functional outcomes were collected. A total of 92 patients were included, predominantly male (75

BACKGROUND:Pouchitis is the most common complication after IPAA for ulcerative colitis. The protective effect of tryptophan metabolites on the mucosal barrier may be effective for treating pouchitis. The role of tryptophan metabolites on pouchitis remained unclear. OBJECTIVE:We aimed to establish a murine model of dextran sulfate sodium-induced pouchitis to examine the roles of tryptophan metabolites in its pathogenesis. DESIGN:This is a study that combines clinical patient data and animal research. A total of 22 patients were enrolled: 5 patients with familial adenomatous polyposis after IPAA, 8 patients with ulcerative colitis after IPAA with pouchitis, and 9 patients with ulcerative colitis after IPAA with normal pouch. The demographic data and fecal samples of patients were collected. Male C57BL/6 mice were purchased from a licensed breeder and underwent IPAA to establish a murine model of the pouch. The blood, feces, and tissues of mice were collected. SETTINGS:This study was performed in an academic medical center in China. INTERVENTIONS:The demographic data of patients were observationally collected. The mice that underwent IPAA were divided into a control group that received a chow diet and 5 study groups: 1) dextran sulfate sodium, 2) 6-formylindolo[3,2-b] carbazole + dextran sulfate sodium, 3) high tryptophan diet + dextran sulfate sodium, 4) CH-223191 + dextran sulfate sodium, and 5) indole-3-carboxaldehyde + dextran sulfate sodium. Animals were euthanized after receiving dextran sulfate sodium for 7 days. MAIN OUTCOME MEASURES:Fecal tryptophan metabolite level and microbiome composition, the severity of pouchitis, intestinal mucosal barrier function, and activation of the aryl hydrocarbon receptor-interleukin 22 pathway were assessed. RESULTS:Patients with pouchitis had lower fecal microbial diversity and indole-3-acetic acid levels. In the murine pouchitis model, high tryptophan diet increased fecal levels of 3-indoleglyoxylic acid, indole-3-aldehyde, and indole. A high tryptophan diet and intraperitoneal aryl hydrocarbon receptor ligand 6-formylindolo[3,2-b] carbazole injection alleviated pouchitis. Tryptophan metabolites improved pouch mucosal barriers. Aryl hydrocarbon receptor inhibitors exacerbated experimental pouchitis and disrupted the mucosal barrier; however, the aryl hydrocarbon receptor ligand indole-3-carboxaldehyde reversed this effect. LIMITATIONS:This study was limited by a small human sample size and lacked an aryl hydrocarbon receptor knockout mouse model. CONCLUSIONS:A high tryptophan diet and aryl hydrocarbon receptor ligand alleviated dextran sulfate sodium-induced pouchitis in a murine IPAA model, which might be achieved through regulating epithelial tight junctions and promoting goblet cell differentiation, as well as maintaining the integrity and function of the mucosal barrier. This study provides a rationale for the clinical application of aryl hydrocarbon receptor ligands in the treatment of pouchitis. See Video Abstract . LOS METABOLITOS DEL TRIPTFANO MEJORAN LA BARRERA DE LA MUCOSA INTESTINAL A TRAVS DE LA VA DEL RECEPTOR DE HIDROCARBUROS ARILOINTERLEUCINA EN LA RESERVORITIS INDUCIDA POR SULFATO DE SODIO Y DEXTRANO EN MODELO MURINO:ANTECEDENTES:La reservoritis es la complicación más frecuente después de la anastomosis del reservorio ileal con el ano en la colitis ulcerosa. El efecto protector de los metabolitos del triptófano sobre la barrera mucosa puede ser un método eficaz para tratar la reservoritis. El papel de los metabolitos del triptófano en la reservoritis sigue sin estar claro.OBJETIVO:Nuestro objetivo era establecer un modelo murino de reservoritis inducida por sulfato de dextrano sódico para examinar el papel de los metabolitos del triptófano en su patogenia.DISEÑO:Este es un estudio que combina datos clínicos de pacientes e investigación animal. Se inscribieron un total de 22 pacientes: 5 con poliposis adenomatosa familiar después de un reservorio ileal, ocho pacientes con colitis ulcerosa después de un reservorio ileal que desarrollaron reservoritis y 9 pacientes con colitis ulcerosa después de un reservorio ileal que no presentaron reservoritis. Se recogieron los datos demográficos y las muestras fecales de los pacientes. Se adquirieron ratones macho C57BL/6 de un criador autorizado y se les realizó un reservorio ileal para establecer un modelo murino del reservorio. Se recogieron sangre, heces y tejidos de los ratones.CONFIGURACIÓN:Este estudio se realizó en un centro médico académico en China.INTERVENCIONES:Los datos demográficos de los pacientes se recogieron de forma observacional. Los ratones sometidos a un reservorio ileal se dividieron en seis grupos: grupo de control con dieta normal, sulfato de dextrano sódico, 6-formilindolo[3,2-b] carbazol + sulfato de dextrano sódico, dieta rica en triptófano + sulfato de dextrano sódico, CH-223191 + sulfato de dextrano sódico, indol-3-carboxaldehído + sulfato de dextrano sódico. Los animales fueron sacrificados después de la administración de sulfato de dextrano sódico durante 7 días.PRINCIPALES MEDIDAS DE RESULTADOS:Se evaluaron los niveles de metabolitos de triptófano y la composición del microbioma fecal, la gravedad de la reservoritis, la función de barrera de la mucosa intestinal y la activación de la vía del receptor de hidrocarburos de arilo-interleucina 22.RESULTADOS:Los pacientes con reservoritis tenían una menor diversidad microbiana fecal y niveles de ácido indol-3-acético. En el modelo de reservoritis murino, la dieta rica en triptófano aumentó los niveles fecales de ácido 3-indolglioxílico, indol-3-aldehído e indol. Una dieta rica en triptófano y una inyección intraperitoneal del ligando del receptor de hidrocarburos de arilo 6-formilindolo[3,2-b] carbazol aliviaron la reservoritis. Los metabolitos de triptófano mejoraron las barreras de la mucosa de la reservoritis. Los inhibidores del receptor de hidrocarburos de arilo exacerbaron la reservoritis experimental y alteraron la barrera mucosa; sin embargo, el ligando del receptor de hidrocarburos de arilo indol-3-carboxaldehído revirtió este efecto.LIMITACIONES:Este estudio estuvo limitado por el pequeño tamaño de la muestra humana y la falta de un modelo de ratón con deficiencia del receptor de hidrocarburos arílicos.CONCLUSIONES:Una dieta rica en triptófano y un ligando del receptor de hidrocarburos arílicos aliviaron la reservoritis inducida por sulfato de dextrano sódico en un modelo murino de anastomosis de reservorio ileo-anal, lo que podría deberse a la regulación de las uniones estrechas epiteliales y la promoción de la diferenciación de las células caliciformes, así como al mantenimiento de la integridad y la función de la barrera mucosa. Este estudio proporciona una justificación para la aplicación clínica de los ligandos del receptor de hidrocarburos arílicos en el tratamiento de la reservoritis. (Traducción-Dr. Felipe Bellolio ).

The colonic mucus layer plays a critical role in maintaining the integrity of the colonic mucosal barrier, serving as the primary defense against colonic microorganisms. Predominantly composed of mucin 2 (MUC2), a glycosylation-rich protein, the mucus layer forms a gel-like coating that covers the colonic epithelium surface. This layer provides a habitat for intestinal microorganisms, which can utilize mucin glycans present in the mucus layer as a sustainable source of nutrients. Additionally, metabolites produced by the microbiota during the metabolism of mucus glycans have a profound impact on host health. Under normal conditions, the production and consumption of mucus maintain a dynamic balance. However, several studies have demonstrated that certain factors, such as dietary fiber deficiency, can enhance the metabolism of mucus glycans by gut bacteria, thereby disturbing this balance and weakening the mucus barrier function of the mucus layer. To better understand the occurrence and development of colon-related diseases, it is crucial to investigate the complex metabolic patterns of mucus glycosylation by intestinal microorganisms. Our objective was to comprehensively review these patterns in order to clarify the effects of mucus layer glycan metabolism by intestinal microorganisms on the host.