Preoperative exclusive enteral nutrition (EEN) improves nutritional status, reduces intestinal inflammation, and likely improves surgical outcomes. Crohn\'s disease exclusion diet with partial enteral nutrition (CDED) also reduces intestinal inflammation but its safety preoperatively is unknown. This single-blinded, multicentre, randomised controlled trial of three preoperative nutritional therapies aimed to assess the feasibility of recruiting and retaining patients and collecting primary and secondary effectiveness outcomes. Adults undergoing elective Crohn\'s disease surgery with a body mass index (BMI) > 18.5 kg/m2 and without significant weight loss were eligible to participate. Patients were randomly assigned to six weeks of preoperative EEN, CDED, or standard care. Feasibility, nutritional, radiological, and surgical outcomes were recorded. Over 18 months, 48 patients were screened, 17 (35%) were randomised, and 13/17 (76%) patients were retained in the intervention phase. It was feasible to collect primary and secondary effectiveness data; at day 30, three patients had Clavien Dindo Grade 2 complications, and 10 had no complications. Nutritional therapy adherence of patients retained in the study was high. Recruitment and retention of patients who need elective Crohn\'s disease surgery for preoperative nutritional therapy is possible, although a shorter duration may improve EEN completion. The impact on surgical outcomes should be assessed in a larger study.

BACKGROUND: Exclusive enteral nutrition (EEN) is an effective treatment for active Crohn\'s disease (CD). This study explored the immunostimulatory potential of a cell-free fecal filtrate and related this with changes in the fecal microbiota and metabolites in children with active CD undertaking treatment with EEN.
METHODS: Production of tumor necrosis factor α (TNFα) from peripheral blood mononuclear cells was measured following their stimulation with cell-free fecal slurries from children with CD, before, during, and at completion of EEN. The metabolomic profile of the feces used was quantified using proton nuclear magnetic resonance and their microbiota composition with 16S ribosomal RNA sequencing.
RESULTS: Following treatment with EEN, 8 (72%) of 11 patients demonstrated a reduction in fecal calprotectin (FC) >50% and were subsequently labeled FC responders. In this subgroup, TNFα production from peripheral blood mononuclear cells was reduced during EEN (P = .008) and reached levels like healthy control subjects. In parallel to these changes, the fecal concentrations of acetate, butyrate, propionate, choline, and uracil significantly decreased in FC responders, and p-cresol significantly increased. At EEN completion, TNFα production from peripheral blood mononuclear cells was positively correlated with butyrate (rho = 0.70; P = .016). Microbiota structure (β diversity) was influenced by EEN treatment, and a total of 28 microbial taxa changed significantly in fecal calprotectin responders. At EEN completion, TNFα production positively correlated with the abundance of fiber fermenters from Lachnospiraceae_UCG-004 and Faecalibacterium prausnitzii and negatively with Hungatella and Eisenbergiella tayi.
CONCLUSIONS: This study offers proof-of concept data to suggest that the efficacy of EEN may result from modulation of diet-dependent microbes and their products that cause inflammation in patients with CD.
Treatment of active Crohn’s disease with exclusive enteral nutrition diminishes the proinflammatory potential of fecal microbial components, hence suggesting a mechanism of action involving modulation of diet-dependent microbes and their products that cause gut inflammation.

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Bevezetés: A kizárólagos enteralis táplálás az elsőként választandó indukciós kezelés gyermekkori, kis kockázatú, luminalis Crohn-betegségben. A Magyar Gyermekkori Gyulladásos Bélbetegség Regiszter adatai alapján ezt a terápiát egyre több centrumban alkalmazzák. Nemzetközi felmérések szerint a kizárólagos enteralis táplálás gyakorlati megvalósítása igen eltérő az egyes centrumokban. Célkitűzés: Vizsgálatunk célja a kizárólagos enteralis táplálás hazai gyakorlatának és az ezzel kapcsolatos nehézségeknek a felmérése volt. Módszer: Online kérdőív alkalmazásával mértük fel a kizárólagos enteralis táplálás gyakorlatát. A 26 kérdésből álló kérdőívet 34 gyermek-gasztroenterológusnak küldtük el. Eredmények: A kérdőívet 21-en (62%) töltötték ki, és a kitöltők minden kérdésre válaszoltak. A válaszadó kollégák több mint fele (57%) mindig kizárólagos enteralis táplálást javasol indukciós kezelésként frissen diagnosztizált Crohn-beteg gyermekeknek. A válaszolók 66,7%-a Crohn-betegek számára fejlesztett, speciális tápszert alkalmaz (66,7%), és többségük a tápszer mellett csak víz fogyasztását engedélyezi (61,9%). Néhányan jóváhagyják keménycukorka, rágógumi vagy tiszta folyadék fogyasztását. Negyedük alkalmaz szondatáplálást oralis intolerancia esetén. Relapsus esetén a megkérdezettek 50%-a javasol ismételten kizárólagos enteralis táplálást. A válaszadók 62%-át segíti dietetikus a munkája során. Következtetés: Összességében elmondható, hogy a hazai gyermek-gasztroenterológusok a nemzetközi gyakorlathoz hasonló arányban, az aktuális ajánlásokat követve alkalmazzák a kizárólagos enteralis táplálást Crohn-betegségben. Orv Hetil. 2024; 165(26): 1002–1009.

Achieving optimal nutritional status in patients with penetrating Crohn\'s disease is crucial in preparing for surgical resection. However, there is a dearth of literature comparing the efficacy of total parenteral nutrition (TPN) v. exclusive enteral nutrition (EEN) in optimising postoperative outcomes. Hence, we conducted a case-matched study to assess the impact of preoperative EEN v. TPN on the incidence of postoperative adverse outcomes, encompassing overall postoperative morbidity and stoma formation, among penetrating Crohn\'s disease patients undergoing bowel surgery. From 1 December 2012 to 1 December 2021, a retrospective study was conducted at a tertiary centre to enrol consecutive patients with penetrating Crohn\'s disease who underwent surgical resection. Propensity score matching was utilised to compare the incidence of postoperative adverse outcomes. Furthermore, univariate and multivariate logistic regression analyses were conducted to identify the risk factors associated with adverse outcomes. The study included 510 patients meeting the criteria. Among them, 101 patients in the TPN group showed significant improvements in laboratory indicators at the time of surgery compared with pre-optimisation levels. After matching, TPN increased the occurrence of postoperative adverse outcomes (92·2 % v. 64·1 %, P = 0·001) when compared with the EEN group. In the multivariate analysis, TPN showed a significantly higher OR for adverse outcomes than EEN (OR = 4·241; 95 % CI 1·567-11·478; P = 0·004). The study revealed that penetrating Crohn\'s disease patients who were able to fulfil their nutritional requirements through EEN exhibited superior nutritional and surgical outcomes in comparison with those who received TPN.

Ustekinumab is an effective therapy for adult Crohn\'s disease (CD), but data in paediatric CD patients are scarce. The aim of the study was to describe the real-life effectiveness and safety of ustekinumab in paediatric CD. This is a multicentre review of children with Crohn\'s disease treated with ustekinumab. The aim of our study was to describe the effectiveness and safety of ustekinumab in paediatric real-life practice. This is a study of the Paediatric IBD (inflammatory bowel disease) Porto group of ESPGHAN. Corticosteroid (CS)- and exclusive enteral nutrition (EEN)-free remission, defined as weighted Paediatric Crohn\'s Disease Activity Index (wPCDAI) < 12.5, and physician global assessment (PGA) were determined at weeks 12 and 52. A total of 101 children were included at a median age of 15.4 years (IQR 12.7-17.2) with a median follow-up of 7.4 months (IQR 5.6-11.8). Ninety-nine percent had received prior anti-TNF, 63% ≥ 2 anti-TNFα therapies and 22% vedolizumab. Baseline median wPCDAI was 39 (IQR 25-57.5) (71 (70%) patients with moderate-severe activity). Weeks 12 and 52 CS- and EEN-free remission were both 40.5%. Clinical response at week 6, iv induction route and older age at onset of ustekinumab treatment were predictive factors associated with clinical remission at week 12. Seven minor adverse events probably related to ustekinumab were reported. One patient died from an unrelated cause.    Conclusion: Our results suggest that ustekinumab is effective and safe in children with chronically active or refractory CD. What is Known: • Ustekinumab is an effective therapy for adult moderate to severe Crohn\'s disease (CD). • Off-label use of ustekinumab in children is increasing especially in anti-TNF refractory CD. What is New: • Is the largest cohort of real-world use of ustekinumab in paediatric CD to date. • Clinical response at week 6, iv induction and older age at onset of ustekinumab were predictive factors associated with clinical response at week 12.

OBJECTIVE: Although biologics were prescribed to achieve and maintain clinical remission of active Crohn\'s disease (CD), almost half of patients experienced a loss of response or intolerance. Here, we investigated the efficacy of combined treatment of biologics and 16-weeks exclusive enteral nutrition (EEN) in moderate-to-severe CD patients with small intestine lesions.
METHODS: This was a real-world, multicenter retrospective study, from October 2016 to March 2023, medical records of patients registered at three IBD centers were reviewed for patients with ileal or ileocolonic CD in moderate-to-severe activity. All patients received treatment of biologics with concomitant 16-week EEN (BioEEN) or biologics alone (Bio). The clinical outcomes and endoscopic outcomes were assessed at week 16 and 52.
RESULTS: There was no statistically significant difference between Bio (97 patients) and BioEEN group (100 patients) at baseline for demographic and clinical characteristics. Compared to treatment with biologics alone, patients with BioEEN treatment achieved higher rates of clinical response (95.0% vs. 66.0%), clinical remission (87.0% vs. 52.6%), endoscopic response (91.4% vs. 47.4%) including mucosal healing (85.7% vs. 23.7%) at week 16. The superiority of BioEEN sustained in maintenance, with 84.7% (vs. 49.1%) clinical response, 77.8% (vs. 38.6%) clinical remission, 69.2% (vs. 32.6%) endoscopic response and 51.9% (vs. 18.6%) mucosal healing at week 52.
CONCLUSIONS: Combined treatment of biologics and 16-week EEN was an efficient therapeutic strategy with affirmative effectiveness for small intestine diseases of active CD.

Crohn\'s disease (CD) is an inflammatory bowel disease. Previous research has explored the impact of diet on CD, as specific dietary components can influence gut microbiota and immune responses, contributing to damage in the gastrointestinal tract. The Crohn\'s Disease Exclusion Diet (CDED) is based on an exclusion diet; it is a recent dietary approach that is often used alongside partial enteral nutrition (PEN) and aims to induce disease remission by excluding certain dietary components. This study assesses the current evidence for the effectiveness of the CDED + PEN in achieving remission in both children and adults with active CD. Our systematic review followed PRISMA recommendations and was registered in PROSPERO with CRD number 42022335076. The searched databases were PubMed/MEDLINE, Cochrane Library, Scopus, and Web of Science. The included studies were analyzed using Rayyan software, and the risk of bias was assessed with Cochrane RevMan 5.0 software. The primary assessed outcome was clinical remission, evaluated with validated questionnaire scores such as PCDAI, CDAI, or HBI. All analyzed papers yielded promising results. Notably, the CDED + PEN demonstrated better tolerance than exclusive enteral nutrition (EEN), resulting in higher adherence rates. Therefore, the CDED + PEN appears to be a viable alternative for induction remission in active disease for both children and adults with CD.

Predicting response to exclusive enteral nutrition (EEN) in active Crohn\'s disease (CD) could lead to therapy personalization and pretreatment optimization.
This study aimed to explore the ability of pretreatment parameters to predict fecal calprotectin (FCal) levels at EEN completion in a prospective study in children with CD.
In children with active CD, clinical parameters, dietary intake, cytokines, inflammation-related blood proteomics, and diet-related metabolites, metabolomics and microbiota in feces, were measured before initiation of 8 wk of EEN. Prediction of FCal levels at EEN completion was performed using machine learning. Data are presented with medians (IQR).
Of 37 patients recruited, 15 responded (FCal < 250 μg/g) to EEN (responders) and 22 did not (nonresponders). Clinical and immunological parameters were not associated with response to EEN. Responders had lesser (μmol/g) butyrate [responders: 13.2 (8.63-18.4) compared with nonresponders: 22.3 (12.0-32.0); P = 0.03], acetate [responders: 49.9 (46.4-68.4) compared with nonresponders: 70.4 (57.0-95.5); P = 0.027], phenylacetate [responders: 0.175 (0.013-0.611) compared with nonresponders: 0.943 (0.438-1.35); P = 0.021], and a higher microbiota richness [315 (269-347) compared with nonresponders: 243 (205-297); P = 0.015] in feces than nonresponders. Responders consumed (portions/1000 kcal/d) more confectionery products [responders: 0.55 (0.38-0.72) compared with nonresponders: 0.19 (0.01-0.38); P = 0.045]. A multicomponent model using fecal parameters, dietary data, and clinical and immunological parameters predicted response to EEN with 78% accuracy (sensitivity: 80%; specificity: 77%; positive predictive value: 71%; negative predictive value: 85%). Higher taxon abundance from Ruminococcaceae, Lachnospiraceae, and Bacteroides and phenylacetate, butyrate, and acetate were the most influential variables in predicting lack of response to EEN.
We identify microbial signals and diet-related metabolites in feces, which could comprise targets for pretreatment optimization and personalized nutritional therapy in pediatric CD.

OBJECTIVE: To investigate the association between disease location and segmental mucosal healing (SMH) following exclusive enteral nutrition (EEN) in children with Crohn\'s disease (CD).
METHODS: Treatment-naive pediatric patients with endoscopically active CD treated with EEN alone as induction therapy were retrospectively enrolled from January 1, 2017 to June 30, 2022. The simple endoscopic score for CD (SES-CD) was employed to score disease activity in the upper gastrointestinal (GI) tract (esophagus, stomach, duodenum), rectum, left colon, transverse colon, right colon, and terminal ileum. While the Lewis score assessed that of the small bowel from the jejunum to the proximal ileum (except the terminal ileum). The variation in the total scores for each segment and SES-CD subscores for each ileocolonic segment from baseline to 1 year after EEN therapy and the segmental endoscopic outcomes and potential predictors associated with SMH for the segments scored by SES-CD were evaluated.
RESULTS: Overall, 82 children with CD were enrolled. Except for the upper GI segment, scores in other segments declined significantly from baseline to EEN completion (all P < 0.001). We analyzed 486 segments (79, 80, 81, 82, 82 and 82 from upper GI tract, terminal ileum, right colon, transverse colon, left colon, and rectum) and found that the segmental SES-CD at baseline (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.55-0.70, P < 0.001) and upper GI location (OR 0.25, 95% CI 0.11-0.55, P = 0.001) were associated with SMH at EEN completion.
CONCLUSIONS: Disease location of the upper GI segment in pediatric CD was associated with SMH following EEN therapy.