Background and aims: The efficacy and underlying mechanisms of exclusive enteral nutrition (EEN) in adult patients with Crohn’s disease (CD) remain controversial. This study aimed to evaluate the role of EEN in adult patients with CD and to explore the mechanisms from the perspective of immunoregulation. Methods: This is a prospective, open-label pilot study. Active patients with CD were enrolled and prescribed an amino-acid-rich elemental diet for 12 weeks. Dynamic changes in immune cells, including neutrophils, monocytes, T cells and B cells, were detected by flow cytometry. Plasma cytokines were evaluated by ELISA. Results: Twenty adult patients with CD were enrolled. Among them, 1 discontinued treatment due to poor compliance, and 19 patients were included for final analysis. Clinical remission was achieved in 47.37% (9/19), 63.16% (12/19), and 73.68% (14/19) patients at weeks 4, 8, and 12, respectively. Endoscopic remission and transmural healing were achieved in 52.63% (10/19) and 15.79% (3/19) patients at week 12. Notably, there was no significant difference in clinical remission between week 4 and week 8 (p = 0.33) or week 12 (p = 0.09). Furthermore, we observed a rapid reconstitution of immunologic homeostasis as early as week 4. At week 4, both the frequency and activation of neutrophils and monocytes were decreased after EEN therapy. Significant decreases in Th17 cells and naïve B cells, increases in memory B cells, and regulatory B cells were also detected. These changes remained stable at weeks 8 and 12. Conclusions: EEN with an amino-acid-rich elemental diet orchestrated immunological balances and induces clinical remission in adult CD patients as early as week 4, suggesting a 4-week EEN therapy may be feasible and practicable in clinical practice.

The aim of this study was to (1) assess the independent factors affecting patients with postoperative intestinal fistula from Crohn disease (CD) by analyzing preoperative clinical data, (2) establish a nomogram prediction model for this condition based on these factors, and (3) validate this model and evaluate its accuracy. In this retrospective multicenter case-control study, the clinical data of 240 patients with CD admitted for surgical treatment between September 2019 and September 2021 at 3 centers were collected. Patients were randomly divided into a training set (168 patients) and a validation set (72 patients). Univariate analysis was performed for relevant factors, and statistically significant factors were then analyzed using multivariate logistic regression to determine the independent influencing factors. A nomogram model for predicting postoperative intestinal fistula in patients with CD was constructed and the accuracy of the model was evaluated using calibration curves. Univariate analysis showed that disease behavior, abdominal abscess, intestinal perforation, neutrophil-to-lymphocyte ratio, systemic immunoinflammatory index, and prognostic nutrition index were factors affecting postoperative intestinal fistula in patients with CD. Multivariate logistic regression analysis showed that neutrophil-to-lymphocyte ratio, prognostic nutrition index, disease behavior, and Crohn disease activity index score were independent influencing factors. After assessing the validation set, the area under the curve was 0.899, indicating good predictive accuracy of the nomogram model. The prediction model developed in this study can effectively predict the risk of postoperative intestinal fistula.

Ustekinumab (UST) is effective for Crohn's disease (CD) but has some limitations. Partial enteral nutrition (PEN) may be helpful for CD remission, yet its ability to augment UST efficacy remains undefined. This study assessed the value of PEN combined with UST as induction and maintenance therapy for CD. Patients with active CD who were treated with UST for over 52 weeks were included from three Inflammatory Bowel Disease centres in China during January 2021 to July 2023. Patients were divided into the UST + PEN group and the UST-alone group according to whether they were combined with PEN (taking enteral nutrition ≥900 kcal/day). Outcomes measured at week 24 (induction phase) and week 52 (maintenance phase) included nutritional/inflammatory markers, CD Activity Index (CDAI), Simple Endoscopic Score for CD (SES-CD), intestinal wall thickness, and blood flow (via intestinal ultrasound or computed tomography enterography). Deep remission, clinical, endoscopic, and radiological response/remission, plus intestinal/perianal complications, were compared using the propensity score weighting method. A total of 229 patients (157 UST-alone and 72 UST + PEN) were enrolled; median PEN intake was 1560 kcal/day (IQR: 900-1800 kcal/day) over a median of 180 days (IQR: 60-309 days). The UST + PEN group achieved a higher rate of clinical remission at week 24 and a superior rate of deep remission, clinical remission, endoscopic response, endoscopic remission, and radiologic response at week 52 (all p < 0.05). The combination therapy group had more benefits in improving intestinal stenosis and perianal disease (both p < 0.05). In addition, the UST + PEN group showed significant improvements in nutritional indicators (hemoglobin and albumin), along with reductions in inflammatory markers. Subgroup analyses further demonstrated the superiority of UST + PEN treatment in TNFi-naïve and TNFi-exposed patients with CD. Notably, a dose- and duration-dependent trend of PEN synergy was observed. Both treatments were well-tolerated with a comparable incidence of adverse events. The combination of PEN and UST significantly enhanced deep remission, and clinical, endoscopic, and radiologic outcomes. It also promoted the improvement of intestinal/perianal complications and improved the levels of inflammatory and nutritional indices in CD. PEN thus served as a valuable adjunct to UST (and potentially other IL-23 inhibitors) for optimizing outcomes, especially in refractory CD with penetrating or stenotic complications.