Background: Growth impairment and poor nutritional status are recognized complications of pediatric inflammatory bowel disease (IBD), yet data specific to ulcerative colitis (UC) are limited. This systematic review aims to provide an overview of current knowledge on growth, nutritional status, and body composition in children and adolescents with UC. Methods: A systematic literature search was performed up to August 2025. Studies including patients aged 5-22 years with confirmed UC were reviewed. Results related to growth, nutritional status, and body composition were narratively synthesized to summarize findings. Results: Fifteen studies with 1575 patients with UC met inclusion criteria, comprising 5 prospective, 5 cross-sectional, and 5 retrospective designs. Although the included studies were conducted in broader IBD cohorts, only UC-specific outcomes were reported. The data were limited by sample size, heterogeneity in patient characteristics, outcome definitions, and assessment methods. The majority of patients had prolonged disease with remission or mild activity. Growth failure prevalence ranged from 7% to 36%, with weight deficits being more common than height deficits. Undernutrition affected up to 25% of patients, with variability across studies. Overweight and obesity were also observed, though most studies showed no significant differences between UC patients and controls. Only five very small studies assessed body composition, reporting inconsistent findings regarding reductions in lean body mass. Conclusions: Growth impairment and poor nutritional status can occur in children and adolescents with UC. Larger, standardized, high-quality studies focused specifically on UC are needed to better characterize its impact on growth and nutritional status, including the essential integration of body composition assessment.

Background:The Crohn's disease (CD) exclusion diet (CDED) is an emerging dietary therapy for inducing remission in CD. However, data on its effects on gut microbiome in adults remain limited. This study investigated microbial responses to CDED in adults with mild-to-moderate CD and compared them with pediatric patients and healthy pediatric controls. Methods:Microbiome data were analyzed from a randomized controlled trial (RCT) in adults (baseline, weeks 6, 12, 24) and a pediatric RCT (baseline, weeks 6, 12). Baseline microbial composition, diversity, and functional potential were compared between patients who achieved sustained clinical remission (SCR) at both weeks 12 and 24 and those who did-not. Functional profiling was performed using gene ortholog annotations, linear discriminant analysis, and metabolite inference. Results:Baseline microbial and functional profiles differed between patients with and without SCR. SCR was associated with lower alpha diversity, higher relative abundances of Alistipes and Faecalibacterium, and increased flagellin gene expression. SCR was associated with enrichment of genes for redox balance, fatty acid metabolism, and DNA repair, while non-SCR showed elevated NAD biosynthesis, bacterial adhesion, and pro-inflammatory pathways. Haemophilus and Prevotella were negatively linked to SCR. Compositional and functional microbiome analyses revealed a microbiome shift during CDED-induced remission toward a profile more similar to healthy pediatric controls. Conclusions:Before and during CDED, distinct baseline microbial and functional profiles were associated with SCR. These highlight the potential of the gut microbiome as a biomarker for identifying patients most likely to benefit from sustained effects of dietary therapy, supporting a more personalized approach to CD management.

Abstract Background The Crohn’s Disease (CD) Exclusion Diet (CDED) is a recognized dietary therapy for managing mild-to-moderate CD in children and adults1,2. This study aimed to compare the effects of CDED on the microbiome in children and adults, based on randomized controlled trials (RCTs) in both cohorts1,2. Methods We analyzed fecal samples from 2 RCTs; one comparing CDED to exclusive enteral nutrition in children over 12 weeks (n:W0 = 69, n:W06 = 57, n:W12 = 52), and the other examining CDED with or without partial enteral nutrition in adults over 24 weeks (n:W0 = 35, n:W06 = 32, n;W12 = 30, n:W24 = 26). We compared the pediatric CDED group with both adult groups, all with mild-to-moderate disease and active inflammation. The V4-V5 region of the 16S rRNA gene was amplified and sequenced, with reads processed through QIIME2 and the SILVA database. Associations between the microbiome, short-term clinical remission and fecal calprotectin (FC) were analyzed using logistic regression, Poisson Principal Component Analysis, Wilcoxon tests, ANOVA, and subsampling ranking forward selection. Results Pediatric patients had higher baseline alpha diversity, which significantly increased by week 12 and was higher in remission compared to adults, who showed a similar but nonsignificant trend. In both pediatric and adult cohorts, baseline Haemophilus abundance was significantly associated with reduced probability of sustained remission (measured at weeks 6 and 12 [pediatric], and 12 and 24 [adults]). Ruminococcus levels increased from baseline to week 6 in patients who did not achieve remission across both cohorts. At week 12, pediatric patients had more taxa associated with achieving remission, whereas adults showed more taxa linked to non-remission. Prevotella was associated with non-remission in both pediatric and adult cohorts, while Akkermansia was linked to non-remission in adults only. By weeks 6 and 12, both cohorts showed increases in Oscillibacter and decreases in Haemophilus.In adults, Alistipes increased over time and was associated with milder disease at baseline for both cohorts. Higher baseline FC in children suggested more severe initial disease. An increase in Firmicutes was associated with lower FC in both cohorts, indicating beneficial microbiome shift in response to CDED. In patients with more severe disease, higher Proteobacteria prevalence was observed, with a stronger difference observed in pediatric than in adult. Conclusion These finding suggest that key microbiome could serve as biomarkers for predicting responses to CDED, enabling more personalized dietary management for CD. Microbial shifts associated with reduced inflammation after CDED, highlight the potential for tailored dietary approaches for both children and adults. References 1.Levine A, Wine E, Assa A et al. Crohn’s Disease Exclusion Diet Plus Partial Enteral Nutrition Induces Sustained Remission in a Randomized Controlled Trial. Gastroenterology. 2019 Aug;157(2):440-450.e8. doi: 10.1053/j.gastro.2019.04.021. 2.Yanai H, Levine A, Hirsch A et al. The Crohn’s disease exclusion diet for induction and maintenance of remission in adults with mild-to-moderate Crohn’s disease (CDED-AD): an open-label, pilot, randomised trial. Lancet Gastroenterol Hepatol. 2022 Jan;7(1):49-59. doi: 10.1016/S2468-1253(21)00299-5.

Abstract Background Crohn’s disease (CD) exclusion diet with partial enteral nutrition (CDED+PEN) and exclusive enteral nutrition (EEN) effectively induce remission in mild-to-moderate paediatric CD. This has been associated with a shift in gut microbiome and metabolome1. The specific mechanisms driving diet-induced remission remain unclear. Microbial biotransformation of bile acids (BAs) is an important metabolic function that has gained increased attention, as three novel microbially-conjugated bile acids (MCBAs) have been found in significantly higher concentrations in CD patients2. We aimed to investigate changes in these MCBAs, specifically Phenylalanocholic acid (Phe-CA), Tyrosocholic acid (Tyr-CA), and Leucocholic acid (Leu-CA), associated with dietary therapies in paediatric CD. Methods BAs and MCBAs concentrations at baseline (W0) and week 6 (W6) were quantified using high performance liquid chromatography in available faecal samples from 23 treatment-naive mild-to-moderate-paediatric CD patients receiving either CDED+PEN (n=12) or EEN (n=11) in a prior RCT3. Clinical remission was defined as PCDAI ≤10. Two comparisons were conducted: (1) W6 remission vs. non-remission to identify if BAs were associated with clinical outcome at W6, and (2) baseline responders (achieving remission at W6) vs. non-responders to identify BAs predictive of W6 remission. ROC analysis and random forest were used to evaluate the predictive power of BAs for clinical remission. Results At W6, 19/23 patients achieved remission (CDED+PEN 9/12, EEN 10/11). Baseline clinical characteristics were comparable between patients achieving remission and no remission. Phe-CA was detected in most samples (19/23 at W0, mean=1.609µM; 12/17 at W6, mean=0.937µM), with W6 levels showing no significant association with clinical outcomes. None of the samples contained detectable levels of Tyr-CA, while only one sample contained detectable Leu-CA. Among CDED+PEN patients, baseline Phe-CA was significantly higher in those who did not achieve remission vs. those who achieved remission at W6 (p<0.0001). ROC analysis of baseline Phe-Ca, 18 other BAs, and their ratios revealed no significant predictive power for clinical outcomes. Conclusion Baseline faecal Phe-CA concentration may serve as a predictive biomarker for CDED+PEN induced remission in paediatric CD. This effect seems independent of other BAs, indicating a unique role of Phe-Ca that could reflect either a specific microbial metabolic activity or the presence of distinct microbiome species. These findings underscore the potential significance of MCBAs in CD and dietary therapies. However, validation in a larger, prospective study is necessary to elucidate the relationship among MCBAs, CD, the microbiome, and diet-induced remission. References 1.Verburgt CM, Dunn KA, Ghiboub M, et al. Successful Dietary Therapy in Paediatric Crohn’s Disease is Associated with Shifts in Bacterial Dysbiosis and Inflammatory Metabotype Towards Healthy Controls. J Crohns Colitis. Jan 27 2023;17(1):61-72. doi:10.1093/ecco-jcc/jjac105 2.Quinn RA, Melnik AV, Vrbanac A, et al. Global chemical effects of the microbiome include new bile-acid conjugations. Nature. 2020/03/01 2020;579(7797):123-129. doi:10.1038/s41586-020-2047-9 3.Levine A, Wine E, Assa A, et al. Crohn’s Disease Exclusion Diet Plus Partial Enteral Nutrition Induces Sustained Remission in a Randomized Controlled Trial. Gastroenterology. Aug 2019;157(2):440-450.e8. doi:10.1053/j.gastro.2019.04.021

Difficulties with feeding and digestion are common in individuals with CHARGE syndrome. Animal models with CHD7 gene variants demonstrate abnormal gut innovation and dysmotility. Our pilot study evaluated whether individuals with CHARGE syndrome have differences in their gut microbiome compared to unaffected siblings. Participants between the ages of 2-18 were recruited from Atlantic Canada with a confirmed genetic diagnosis of CHARGE syndrome. Gut Microbiome DNA analysis was performed on stool samples using 16S ribosomal RNA (rRNA) gene sequences. The PASSFP and PEDSQL served as GI symptom questionnaires. Eleven participants completed this study with one twin pair (CHARGE syndrome = 7, sibling controls = 4). The mean percent abundance for the four most common phyla in individuals with CHARGE versus Controls showed a trend towards increased Bacteroidetes, Proteobacteria, and a decrease in Firmicutes and Actinobacteria but was not significant. Microbiome comparisons based on abnormal (< 77) and normal ( ≥  77) GI scores, found significantly elevated Bacteroidetes (p = 0.042, 59.5% ± 15.1% vs. 33.1% ± 14.6%) and decreased Firmicutes (p = 0.042, 37.5% ± 15.9% vs. 62.4% ± 14.0%) with abnormal scores. Alpha diversity did not differ with either disease or GI symptom scores. Our data showed that, although there was a trend in changes in the gut microbiome in individuals with CHARGE compared to unaffected siblings, this change appears to be related to the severity of GI symptoms and not necessarily CHARGE itself, as differences were more pronounced in individuals with more difficulties with feeding and GI symptoms.

Objectives Chronic nonbacterial osteomyelitis (CNO) is a rare, sterile autoinflammatory bone disorder that can develop in patients with inflammatory bowel disease (IBD). We aimed to identify the clinical features and natural history of patients with a dual diagnosis of CNO and IBD. Methods Medical records of patients with a dual diagnosis of IBD and CNO were reviewed in centers from the Paediatric IBD Porto Group and IBD Interest Group of ESPGHAN. Collected data included demographic characteristics, disease features, laboratory studies, bone imaging findings, and clinical outcomes. Results Forty‐five patients (24 [53%] males), were included. Median age at the time of dual diagnosis was 10 (interquartile range [IQR]: 12–13) years. Thiry‐two (71%) patients were diagnosed with Crohn's disease, and 14 (44%) of them exhibited perianal disease. CNO presented in 15 patients (33%) within 3 months of IBD diagnosis, and in additional 20 (44%) patients after IBD diagnosis. In most patients, CNO manifested while IBD was clinically active, but not necessarily. However, in 10 (22%) patients CNO preceded the diagnosis of IBD with a median time 46 (25–248) weeks. Upon diagnosis of CNO, most patients were treated with anti‐tumor necrosis factor. CNO remission was achieved in all patients at some point during follow‐up; However, complications occurred in six patients and included vertebral collapse, bone fracture, and bone deformity. Conclusions CNO can be associated with active or quiescent intestinal inflammation, manifesting before, during, or after the diagnosis of IBD. While CNO remission was achieved in all patients, some developed significant bone complications.

Background and Aims Therapeutic drug monitoring (TDM) of methotrexate (MTX) is challenging due to its pharmacokinetics and short plasma half-life. Intracellular MTX-polyglutamates (PG(1-5)), which accumulate over time, have not been assessed in pediatric inflammatory bowel disease (IBD). This study aimed to evaluate erythrocyte MTX-PG as a potential TDM tool in pediatric IBD. Methods In this cross-sectional study, MTX-PG concentrations were measured in erythrocytes of children with IBD on stable low-dose MTX for at least 12 weeks using stable-isotope dilution liquid chromatography-tandem mass spectrometry. The influence of administration route, MTX dosage, and anthropometrics on MTX-PG concentrations was examined. Results Seventy-eight patients were included, showing MTX-PG(3) as the predominant subspecies (median 27.0 nmol/L) with a median MTX-PG(total) of 74.8 nmol/L. A higher MTX dose correlated significantly with elevated levels of MTX-PG(3), MTX-PG(4), MTX-PG(5), and MTX-PG(total) (P < .01). Adjusted for body surface area, MTX dose remained significantly associated with higher MTX-PG concentrations (P < .01). However, comparison by administration route was limited due to a few patients on subcutaneous MTX (n = 4). Conclusions We observed high interindividual variability in the reached erythrocyte MTX-PG concentrations. Body surface adjusted or unadjusted MTX dosage showed a positive linear correlation with erythrocyte MTX-PG concentrations in children with IBD. This is a prerequisite for TDM and provides a strong basis for further research into the relation between TDM of MTX, efficacy, and toxicity.

Background Perturbations of the gut microbiota in patients with inflammatory bowel disease (IBD) have been extensively characterised, but changes to the oral microbiome remain understudied. This study aimed to evaluate the oral microbiome of adults with IBD and of matched controls.Methods Saliva samples and data were obtained from a Canadian population cohort (n = 320). The salivary microbiome was characterised using 16S rRNA gene sequencing and examined for differences between control participants and those with IBD, as well as disease subcategories (Crohn’s Disease and Ulcerative Colitis).Results Alpha diversity was significantly lower in participants with IBD than controls in unadjusted models and many remained significant after adjusting for covariates. Significant differences in some beta diversity metrics between participants with IBD and controls were found, although these did not remain significant when adjusted for covariates. Ten genera were significantly differentially abundant between cases and controls. Veillonella and Streptococcus were both increased in abundance in IBD cases vs controls (25% vs 22% and 14% vs 12%, respectively).Conclusion These results showcase changes in oral microbial diversity and composition in those living with IBD and highlight the potential of using the salivary microbiome as a biomarker for screening or monitoring IBD.

Acute severe colitis (ASC) is a relatively frequent manifestation in children with ulcerative colitis and one of the few emergencies in paediatric gastroenterology. A standardized proactive approach based on tight monitoring and timely medical and surgical interventions may improve patients' outcomes. We aimed to update the previous ASC guidelines using detailed recommendations and practice points, based on a systematic review of the literature and consensus of experts. These guidelines update is a joint effort of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition and the European Crohn's and Colitis Organization. A systematic search was performed in Pubmed Ovid Medline, Embase and Cochrane databases using 13 predefined PICO (patient, intervention, comparison, outcomes) based questions and 30 non-PICO based questions. Grading methodology was based on the Oxford Centre for Evidence-Based Medicine-Levels of evidence. The questions were addressed by working subgroups following an iterative consensus voting process, including three online voting meetings and one face-to-face meeting. A total of 36 recommendations and 72 practice points were endorsed with a consensus rate of at least 88% for all statements, regarding initial evaluation, monitoring, medical and surgical treatment of ASC in children. Several topics have been revised since the previous 2018 guidelines and differ from corresponding published adult guidelines. These guidelines present a comprehensive overview of the management of ASC in children, offering practical recommendations and practice points aiming to standardize clinical and surgical treatment and improve outcomes of this severe scenario.

OBJECTIVES:Despite advances in the management of ambulatory paediatric ulcerative colitis (UC), challenges remain as many patients are refractory to therapy and some require colectomy. The aim of these guidelines is to provide an update on optimal care for UC through detailed recommendations and practice points. METHODS:These guidelines are an update to those published in 2018 and are a joint effort of the Paediatric IBD Porto group of European Society of Paediatric Gastroenterology, Hepatology and Nutrition and the European Crohn's and Colitis Organisation. An extensive literature search with subsequent evidence appraisal using the Oxford methodology was performed, followed by three online voting sessions and a consensus face-to-face meeting. Thirty-nine recommendations and 77 practice points were endorsed by the 25 experts with at least an 84% consensus rate. RESULTS:Robust evidence-based recommendations and detailed practice points are provided. In addition to reemphasising and updating the role of more 'traditional' UC therapies, these guidelines outline optimising the use of antitumour necrosis factor therapies and integrating newer biologics and small molecules, as well as supportive therapy, to improve outcomes and provide an updated management algorithm. Measurement and monitoring tools and decision aids are provided, and additional aspects, including nutritional support, extraintestinal manifestations, pouchitis, inflammatory bowel disease-unclassified and patient support, are discussed. Some aspects, including surgery and thromboprophylaxis, are covered in the acute severe UC guidelines. CONCLUSIONS:These guidelines serve as an aid in managing children with UC through a combination of evidence-based recommendations and more practical practice points in the ambulatory setting.

BACKGROUND:The use of concomitant azathioprine may improve efficacy and pharmacokinetic (PK) properties of infliximab (IFX) but is also associated with an increased risk of adverse events. Proactive therapeutic drug monitoring (pTDM) of IFX monotherapy is an alternative strategy to improve PK. The aim of this study was to evaluate whether IFX with an immunomodulator (combo) has PK benefits over IFX-pTDM (mono) in pediatric Crohn's disease (CD). METHODS:This PK analysis included pediatric CD patients who started either IFX combo (TISKids study) or IFX mono with pTDM (REFINE cohort). Combo and mono IFX trough levels (TLs) and antibodies-to-infliximab were assessed at infusion 3, 4, and 5. A population PK model was built to compare IFX PK outcomes (clearance [CL], TLs and cumulative exposure) between combo and mono groups at infusion 4 and 5. Clinical response and steroid-free clinical remission (SFCR) was assessed at infusion 4 and 5. RESULTS:This study included 128 pediatric CD patients (66 mono and 62 combo). At infusion 5, there was no significant difference between mono and combo median TLs 4.1 µg/mL (2.1, 7.8) vs 5.9 µg/mL (3.2, 9.4; P = .14) or median CL 0.26 L/d (0.21, 0.32) vs 0.26 L/d (0.21, 0.33; P = .81). Mono patients had a lower SFCR rate at infusion 5 (53% [31 of 59] vs 80% [32 of 40]; P = .01). Clinical response rates were significantly higher among combo than mono patients at both infusion 4 and 5. CONCLUSIONS:This study suggests that there are no PK differences (TLs and CL) between combo and mono therapy in pediatric CD patients who started IFX.

Abstract Background The Crohn’s Disease Exclusion Diet (CDED) with partial enteral nutrition can induce remission in patients with mild-to-moderate Crohn’s disease. As adherence is the key of (possibly) success of a medical therapy and CDED might be a complicated diet to perform, we aimed to investigate patients’ experience with CDED and the available tools (Modulife programme) to improve patientcare. Methods All mild-to-moderate active Crohn’s disease (CD) (adult and pediatric) patients treated with CDED as nutritional therapy as part of their medical treatment at Amsterdam UMC between 2019-2022 were approached for this retrospective qualitative study. A structured telephone interview was conducted by a dedicated dietician/doctor with the patients and/or parent/guardian in case of children. Questions about CDED-experience and Modulife program were either measured with the NET Promotor Score (NPS -100 - +100), as yes/no answer options or with 5-point likert scales (1=strongly agree/always to 5=strongly disagree/never). Lastly, patients were asked to evaluate the effectiveness of CDED on complaints and experience on a scale from 0-10. Results 44 patients (33 pediatric/11 adults; 26 women) participated in the interviews. The majority (61%) of the pediatric patients started CDED at diagnosis. The remaining 39% started 1-11 years (median 3[IQR 2-5]) after diagnosis at an age of 7-17 years (median 15[IQR 12-16]). 91% of the adult patients started CDED 3-37 years (median 11[IQR 4-28]) after diagnosis and only 1 immediately after diagnosis at an median age of 48 [IQR 33-60] (range: 19-69). The majority of the pediatric participants would recommend CDED to others (77%) and consider to start the diet again (55%). All of the adults would recommend CDED to others and consider to start CDED again. The NPS scores on CDED experiences are shown in figure 1. The median score for the effect of the diet on complaints was 8[IQR 5-9] (range 0-10) and 7[IQR 6-7](range 2-8.5) for experience. The majority of the patients (75%) used the Modulife program always or often during therapy and did (strongly) agree that the Modulife program was helpful. A NPS of 31 was given for recommending the app to others. The recipes-feature was the most used and most esteemed part of the app and was assessed with a good NPS of 27 for recommendation to others. Conclusion The majority of the pediatric and all of the adult participants would recommend CDED to others and would reconsider starting the diet again. CDED is better assessed by adults (positive NPS) then children and/or their parents (negative NPS). Most of the patients, assess the Modulife programme very positively and the majority would rate this as helpful in performing the diet.

BACKGROUND & AIMS:The Crohn's disease exclusion diet (CDED) + partial enteral nutrition (PEN) is effective for inducing remission in mild-moderate Crohn's disease (CD). We assessed whether a 2-week course of exclusive enteral nutrition (EEN) followed by CDED+PEN is superior to 8 weeks of EEN in sustaining clinical remission at week 14 in mild-to-severe CD and if CDED+PEN can maintain remission to week 24. METHODS:This international, multicenter, randomized controlled trial compared 2 weeks of EEN (Modulen IBD) followed by 3 phases of the CDED+PEN (henceforth CDED) to 8 weeks of EEN, followed by PEN with free diet up to week 24 (henceforth EEN). RESULTS:Out of 64 eligible patients, 56 were randomized (target recruitment failed due to the COVID-19 pandemic, leading to an underpowered study): 30 patients to CDED and 26 to EEN. The primary endpoint at week 14 showed no significant difference between the groups, with sustained corticosteroid-free remission in 21 (70%) of 30 for CDED compared with 16 (61.5%) of 26 for EEN (P = .5). At week 8, clinical remission was achieved in 23 (77%) of 30 CDED patients vs 14 (54%) of 26 EEN patients (P = .07), and 18 (60%) of 30 CDED patients vs 11 (42%) of 26 EEN patients maintained clinical remission to week 24 (P = .18). The body mass index Z score significantly improved in the CDED group but not in the EEN group. CONCLUSIONS:The study was underpowered to show whether CDED was superior to EEN in sustaining remission. However, 2 weeks of EEN followed by CDED was effective in inducing remission in CD, with most CDED patients maintaining remission up to 24 weeks. Despite dietary restrictions for 24 weeks, the body mass index Z score improved significantly in the CDED group but not in the EEN group (NCT02843100).

Literature on dietary behaviours of the pediatric Crohn’s Disease (CD) population and the relationship between dietary intake and CD activity is limited. Three dietary indices were developed and tested to conduct dietary pattern analysis in pediatric patients with CD consuming a free diet following remission induction via exclusive enteral nutrition (n = 11). Index scores underwent descriptive and inferential analysis. The mean adjusted scores (out of 100) for the Pediatric Western Diet Index, Pediatric Prudent Diet Index, and Pediatric-Adapted 2010 Alternate Healthy Eating Index (PA2010-AHEI) were 29.82 ± 15.22, 34.25 ± 15.18, and 51.50 ± 11.69, respectively. The mean Western-to-Prudent ratio was 0.94 ± 0.55. A significant correlation (r = −0.71) and relationship (F[1, 9] = 9.04, P < 0.05, R2 = 0.501) between the Western-to-Prudent ratio and PA2010-AHEI was found. The results suggest participants were not following a Western or Prudent diet, and were consuming foods not captured by the indices. More research is needed to describe dietary intake of individuals with CD, validate dietary indices in diverse samples, and explore the utility of these indices in CD assessment and treatment. The co-authors hope this work will stimulate/inspire subsequent interprofessional, dietitian-led research on this topic.

Background: The Crohn’s Disease Exclusion Diet (CDED) is a whole-foods regimen that has demonstrated efficacy in inducing remission among children and adults with mild-to-moderate disease. While initial studies predominantly originated from Israel, recent years have witnessed the expansion of experiences to diverse cultures, culminating in the recognition of CDED in the latest ESPEN guidelines. However, implementing dietary therapy poses significant challenges across various cultures, necessitating adaptations. Aim and Methods: This case-based study aims to present the collective experience from different cultures, shedding light on the encountered challenges and the corresponding solutions devised to surmount them by convening healthcare providers (dietitians and physicians across six countries and eight cultural settings) with extensive experience in utilizing the CDED. Results and Conclusions: Our findings underscore the efficacy of CDED across diverse cultural contexts and emphasize the pivotal role of dietitians in tailoring the diet to accommodate patients’ cultural behaviors and traditions. We highlight challenges encountered and delineate strategies for overcoming them by customizing the diet and offering tailored guidance. Additionally, we provide insights into implementing CDED in various regions through adjusted recipes and personalized counseling from dietitians. This study contributes to the growing body of literature on CDED, and offers practical guidance for its effective adoption in diverse cultural settings.

Abstract Background Methotrexate (MTX) is increasingly prescribed in paediatric inflammatory bowel disease (IBD), but therapeutic drug monitoring (TDM) is currently not feasible due to its characteristic pharmacokinetics and short half-life in plasma, which amounts to approximately 2.5-6.5 hours. Because of this, plasma MTX is no longer detectable shortly after administration. However, MTX-polyglutamates (PG1-5) are formed intracellularly and accumulate over time. Recently, we developed a technique for targeted erythrocyte MTX-PG analysis with the potential for TDM. Data in paediatric IBD with this technique are lacking so far. Here, we aimed to identify the potential of erythrocyte MTX-PG analysis to measure MTX levels in paediatric IBD. Methods In this observational cross-sectional study, we determined MTX-PG concentrations in erythrocytes retrieved from blood samples of paediatric IBD patients on low-dose MTX maintenance therapy, defined as exposure to a stable dose of MTX for at least twelve consecutive weeks. MTX-PG concentrations were determined by stable-isotope dilution liquid chromatography mass-spectrometry. Furthermore, we evaluated the effects of route of administration (oral versus subcutaneous), MTX dosage, and anthropometric data on MTX-PG concentrations. Results Fifty-two paediatric IBD patients on MTX maintenance therapy were included. The predominant subspecies was MTX-PG3 (mean 30.5 nmol/L, SD ± 20.0) and the mean MTX-PGtotal concentration was 88.6 nmol/L (SD ± 52.6). A higher dose was linearly associated with significantly higher MTX-PG3 (r = 0.56), MTX-PG4 (r = 0.52), MTX-PG5 (r = 0.48) and MTX-PGtotal (r = 0.49) levels. When adjusted for body surface area, MTX dose was also linearly associated with significantly higher MTX-PG3 (r = 0.51), MTX-PG4 (r= 0.39), and MTX-PGtotal (r= 0.40) concentrations. A reliable comparison regarding route of administration was not possible in this cohort, due to the small number of patients receiving subcutaneous MTX (n=3). Conclusion We observed high inter-individual variability in the reached erythrocyte MTX-PG concentrations. Body surface adjusted or unadjusted MTX dosage showed a positive linear correlation with erythrocyte MTX-PG concentrations in children with IBD. This is a prerequisite for TDM and provides a strong basis for further research into the relation between TDM of MTX, effectivity and toxicity.

Abstract Background The Crohn's Disease (CD) Exclusion Diet (CDED) is an established dietary therapy for children with active mild-to-moderate CD. A recent randomized controlled trial showed efficacy in mild-to-moderate CD in adults. We have previously demonstrated the impact of CDED on the microbiome of children. The aim of this work was to assess if we can determine sustained clinical remission (SCR) from the baseline microbiome composition and examine the effect of CDED on microbiome composition in adult CD. Methods This was an open-label, prospective, randomized, controlled pilot trial involving patients with mild-to-moderate CD and evidence of active inflammation. Patients were randomly assigned to receive CDED with partial Enteral Nutrition (PEN) or CDED alone, both for 24 weeks. The V4V5 region of the 16S rRNA gene was amplified and sequenced, and reads were processed using QIIME2 and the SILVA database. Relationships between the microbiome, SCR, and Fecal Calprotectin (FC) were analyzed using logistic regression, Poisson Principal Component Analysis, paired T-Tests and subsampling ranking forward selection. Results Clinical remission (CR) at weeks 6, 12 and 24 was achieved in 62.5%, 52.5%, and 50% of patients, respectively. Week 0, 6, 12 and 24 stool samples were available for 35,32,30 and 26 patients, respectively. In patients with SCR, defined as remission at both weeks 12 and 24, the baseline microbiome revealed lower alpha diversity compared to those without SCR (p=0.018), and differing Microbiome principal components (PC) scores (p < 0.01). PC1 and PC3, characterized mainly by Alistipes, Faecalibacterium and UCG-002 predicted SCR (P<0.01). PC2 predicted elevated FC>250 µg/g at week 12 (p=0.004). Baseline abundance of Haemophilus was associated with decreased SCR probability (p<0.01). At week 6 in the entire cohort, there was a significant decrease in Actinobacteriota (p=0.035) and a significant increase in Bacteroidota (p=0.003). Additionally, there was a significant increase in several genera, including beneficial Alistipes and Oscillibacter (p<0.02) in those who achieved CR after 6, 12, or 24 weeks. Higher Firmicutes at week 6 were associated with FC<250 at week 12 (p=0.031). An uncultured genus from the Oscillospiraceae family was significantly associated with a decrease in the probability of SCR (p<0.01) and was significantly increased at week 6 in patients who did not attain CR (p<0.05). Conclusion The baseline microbiome composition was associated with SCR and FC<250 at week 12 in adult patients treated with CDED (with or without PEN) over 24 weeks. This suggests that the microbiome could be useful tool to identify patients who would benefit from long-term dietary intervention.

Dietary therapy is increasingly recognized for the management of Crohn's disease (CD) over recent years, including the use of exclusive enteral nutrition (EEN) as first-line therapy for pediatric CD according to current guidelines. The Crohn's disease exclusion diet (CDED) is a whole-food diet designed to reduce exposure to dietary components that are potentially pro-inflammatory, mediated by negative effects on the gut microbiota, immune response, and the intestinal barrier. The CDED has emerged as a valid alternative to EEN with cumulative evidence, including randomized controlled trials, supporting use for induction of remission and possibly maintenance in children and adults. We gathered a group of multidisciplinary experts, including pediatric and adult gastroenterologists, inflammatory bowel diseases (IBD) expert dietitians, and a psychologist to discuss the evidence, identify gaps, and provide insights into improving the use of CDED based on a comprehensive review of CDED literature and professional experience. This article reviews the management of CDED in both children and adults, long-term aspects of CDED, indications and contraindications, selecting the best candidates, identifying challenges with CDED, globalization, the role of the multidisciplinary team, especially of dietitian, and future directions. We concluded that CDED is an established dietary therapy that could serve as an alternative to EEN in many pediatric and adult cases, especially with mild to moderate disease. In severe disease, complicated phenotypes, or with extraintestinal involvement, CDED should be considered on a case-by-case basis, according to physician and dietitians' discretion. More studies are warranted to assess the efficacy of CDED in different scenarios.

Abstract Background Chronic Recurrent Multifocal Osteomyelitis (CRMO) is a rare, autoinflammatory bone disorder. CRMO was linked with inflammatory bowel disease (IBD), either as an extra intestinal manifestation or as a paradoxical effect of anti-TNFa therapy. Our goal was to define the clinical features and natural history of patients carrying a dual diagnosis of CRMO and IBD Methods Medical records of pediatric patients with a dual diagnosis of IBD and CRMO were reviewed in nineteen centers from the Paediatric IBD Porto Group of ESPGHAN. Collected data included demographic characteristics, disease features, laboratory studies, bone imaging findings and outcomes of each disease Results Forty five patients (21 [47%] females) with a diagnosis of CRMO and IBD (32 [71%] with Crohn’s disease) were included. Median age at the time of dual diagnosis was was 10.2 (IQR 12-13.5) years. Patients were divided into 3 groups, based on whether CRMO developed before, during or after IBD diagnosis. In 15 patients (33%), CRMO was diagnosed ±3 months from the time of IBD diagnosis, with 8 (53%) and 2 (13%) exhibiting mild and moderate-severe IBD activity, respectively. In 20 children (44%) IBD preceded CRMO diagnosis by >3 months with a median time of 238 (85-344) weeks. At the time of dual diagnosis, 12 (60%) patients were in IBD remission and 5 (25%) exhibited moderate-severe disease activity; however, CRP and ESR were elevated (1.5 [0.4-3.4] mg/dL and 35 [21-55] mm/h, respectively) while median fecal calprotectin was 567 (68-1800) mcg/gr, including 4 patients <100 mcg/gr. 17 patients (85%) were on anti-TNFa medication at the time CRMO developed. In 10 (22%) patients CRMO preceded the diagnosis of IBD (>3 months before IBD evolution) with a median time 46 (25-248) weeks. At time of IBD presentation, CRMO was in remission in 5 patients (50%). 4 patients were diagnosed with IBD, despite the lack of any abnormal gastro-intestinal symptoms. In patients in which CRMO was diagnosed after or during IBD diagnosis, different therapeutic regimens were used, including anti-TNFa agents, methotrexate, ustekinumab, NSAID’s and corticosteroids. Two patients also received bisphosphonates. In patients in which CRMO was diagnosed after or during IBD diagnosis, CRMO remission, defined as lack of bone pain, was achieved in 22.2 (15-51.8) weeks. CRMO complications occurred in 4 patients and included vertebral collapse, length discrepancy, bone fracture and bone deformity Conclusion In the largest cohort to date, CRMO presentation was not necessarily related to clinically active intestinal inflammation and could present before, during or after IBD diagnosis. CRMO remission was achieved in all patients; Nevertheless, a small number of patients developed significant bone complications

Abstract Background Exclusive enteral nutrition (EEN) is the first-line treatment for active Crohn’s disease (CD) in children. CD Exclusion Diet (CDED) combined with Partial Enteral Nutrition (PEN) has demonstrated better tolerance with a comparable effect in inducing remission among children with mild to moderate CD. This study evaluated the effectiveness of 2 weeks of EEN followed by CDED+PEN for maintaining remission for up to 24 weeks in children with mild-severe disease. Methods We conducted an international, multicenter, randomized controlled trial comparing 2 weeks of EEN using Modulen®, followed by 3 phases of the CDED+PEN (hereafter CDED), to 8 weeks of EEN followed by PEN with a free diet (hereafter EEN), all extended up to week 24 with a follow up till week 52. Children aged 8-18 with luminal CD duration less than 3 years, mild-severe disease [pediatric CD activity index (PCDAI),15-47.5], and active inflammation [elevated C-reactive protein (CRP),or fecal calprotectin (FC)] were included. Remission was defined as PCDAI≤10. Stable immunomodulator (IM) treatment was allowed, and naïve patients could initiate IM from week 4. Results We randomized 56 patients into two groups: Group CDED (n=30) and Group EEN (n=26); mean age 12.7±2.4, 37% female. Intention-to-treat analysis revealed remission in 18/30(60%) patients with CDED compared to 11/26(42%) with EEN at week 24,p=0.18 and 27% in CDED and 23% in EEN at week 52,p=0.75. Per protocol analysis showed 18/20(90%) remission in CDED compared to 11/14(78%) in EEN at week 8, p=0.35. Among patients who achieved remission at week 8, 18/23(78%) with CDED and 9/14(64%) with EEN maintained remission up to week 24, p=0.15. In CDED,15/20(75%) and 100% of EEN used IM, p=0.04. All CDED patients without IM remained in remission. Reduction of >50% in FC from baseline was obtained in 55% in the CDED and 28% in EEN, p=0.12. PCDAI improved from 31.2[20-35.6] to 5[0-12.5] in CDED and from 22.5[20-29.3] to 5[0-15.6] at week 24 in EEN, p<0.001 to all. CRP and FC significantly improved in both groups. Z score BMI improved from -1.3 [-2.1-(-0.1)] to -0.2 [-0.9-0.4], p=0.003 in CDED and from 0.08[-1.1-0.4] to 0.2[-1.7-0.7] at week 24 in EEN,p=0.098. Remission at week 2 (p=0.006) and overall high compliance (p=0.009) were identified as predictors of response at week 24. Conclusion While 2 weeks of EEN followed by CDED+PEN was not superior to EEN at 14 weeks (as previously reported), extending CDED+PEN for 24 weeks successfully maintained remission for up to 52 weeks in children with mild-to-severe CD. Moreover, a subset of patients maintained sustained clinical remission following CDED monotherapy. The long-term implementation of dietary therapy using CDED+PEN resulted in a significant improvement in nutritional status.