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Copyright of Chinese Journal of Contemporary Pediatrics is the property of Xiangya Medical Periodical Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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. [ABSTRACT FROM AUTHOR]

Background Azathioprine [AZA] effectively prevents postoperative endoscopic recurrence [ER] in Crohn's disease [CD]. However, the efficacy of AZA emerges after 3 months. Exclusive enteral nutrition [EEN] can maintain remission in CD. The present trial investigates whether AZA plus postoperative 3-month EEN is superior to AZA alone in preventing ER of CD. Methods In total, 84 high-risk CD patients undergoing intestinal resection received AZA alone or AZA plus 3 months of EEN [AZA + EEN] postoperatively. The primary endpoint was the rate of ER at 12 months. Secondary endpoints included the rate of ER at 3 months, clinical recurrence [CR], CD activity index [CDAI] scores, faecal calprotectin [FC], and C-reactive protein [CRP]. Quality of life was assessed using Short Form-36 [SF-36] and the Inflammatory Bowel Disease Questionnaire [IBDQ]. Results Patients in the AZA + EEN group exhibited significantly lower rates of ER compared to the AZA group at both 12 months (33.3% [13/39] vs 63.2% [24/38], P  = 0.009) and 3 months (8.6% [3/35] vs 28.1% [9/32], P  = 0.037) post-surgery. The rates of CR between the two groups at 3 and 12 months were similar. CDAI scores, FC, albumin level, and CRP were all comparable between the two groups. Quality of life was significantly higher in the AZA group than in the AZA + EEN group at 3 months but became comparable from 5 to 12 months postoperatively. Conclusion In high-risk CD patients, combining AZA with postoperative 3-month EEN reduces 1-year ER but may temporarily impact quality of life. Further large-scale, long-term studies are warranted. Trial Number NCT05214430. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Copyright of Hungarian Medical Journal / Orvosi Hetilap is the property of Akademiai Kiado and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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. 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. 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. Combined treatment of biologics and 16-week EEN was an efficient therapeutic strategy with affirmative effectiveness for small intestine diseases of active CD. [ABSTRACT FROM AUTHOR]

Summary: Background: Mesenteric adipose tissue (mAT) hyperplasia, known as creeping fat, is a pathologic characteristic of Crohn’s disease (CD). In our previously reported cohort, we observed that Achromobacter pulmonis was the most abundant and prevalent bacteria cultivated from creeping fat. Methods: A whole genomic sequencing and identification of T3SS orthologs of mAT-derived A. pulmonis were used. A functional type III secretion system (T3SS) mediated the pathogenic potential of A. pulmonis in vitro and in mouse colitis model. Furthermore, a T3SS Finder pipeline was introduced to evaluate gut bacterial T3SS orthologs in the feces of CD patients, ulcerative colitis and colorectal cancer patients. Findings: Here, we reveal that mAT-derived A. pulmonis possesses a functional T3SS, aggravates colitis in mice via T3SS, and exhibits T3SS-dependent cytotoxicity via a caspase-independent mechanism in macrophages and epithelial cells, which demonstrated the pathogenic potential of the T3SS-harboring A. pulmonis. Metagenomic analyses demonstrate an increased abundance of Achromobacter in the fecal of Crohn's disease patients compared to healthy controls. A comprehensive comparison of total microbial vT3SS abundance in various intestine diseases demonstrated that the specific enrichment of vT3SS genes was shown in fecal samples of CD, neither ulcerative colitis nor colorectal cancer patients, and ten T3SS gene-based biomarkers for CD were discovered and validated in a newly recruited CD cohort. Furthermore, treatment with exclusive enteral nutrition (EEN), an intervention that improves CD patient symptomatology, was found associated with a significant reduction in the prevalence of T3SS genes in fecal samples. Interpretation: These findings highlight the pathogenic significance of T3SSs in the context of CD and identify specific T3SS genes that could potentially function as biomarkers for diagnosing and monitoring the clinical status of CD patients. Funding: This work is supported by the National Key Research and Development Program of China (2020YFA0907800), the China Postdoctoral Science Foundation (2023M744089), the National Natural Science Foundation of China (32000096), the Shenzhen Science and Technology Programs (KQTD20200820145822023, RCIC20231211085944057, and ZDSYS20220606100803007), National Key Clinical Discipline, Guangdong Provincial Clinical Research Center for Digestive Diseases (2020B1111170004), Qingfeng Scientific Research Fund of the China Crohn’s & Colitis Foundation (CCCF) (CCCF-QF-2022B71-1), and the Sixth Affiliated Hospital, Sun Yat-sen University Clinical Research 1010 Program 1010CG(2023)-08. These funding provided well support for this research work, which involved data collection, analysis, interpretation, patient recruitment and so on.

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. [ABSTRACT FROM AUTHOR]

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. Conclusion: Disease location of the upper GI segment in pediatric CD was associated with SMH following EEN therapy. [ABSTRACT FROM AUTHOR]

Background: Adalimumab monotherapy can suppress gut inflammation and induce remission in active Crohn's disease but has some limitations. Exclusive enteral nutrition (EEN) is recommended for patients with mild to moderate Crohn's disease (CD), but implementation is challenging. Aim: To evaluate the effectiveness of adalimumab combined with partial enteral nutrition (PEN) in the induction therapy for Crohn's disease. Methods: A prospective cohort study was designed and a total of 56 patients with active CD who met the criteria for enteral nutrition (EN) treatment in our hospital were selected. The baseline data of all patients were collected including age, sex and other general information. The changes in fecal calprotectin, C-reactive protein (CRP), albumin(Alb), hemoglobin (Hb), platelets (Plt), erythrocyte sedimentation rate (ESR), Crohn's disease activity index score (CDAI), simple endoscopic score (SES-CD) and body mass index (BMI) were compared between the adalimumab combined with enteral nutrition (ADA+EN) group (N = 37) the adalimumab group (ADA) (N = 19) at week 0 (W0) and treatment outcomes at week 12(W12). Additionally, the differences between the two groups before and after treatment were evaluated. Then the ADA+EN group was divided into an adalimumab combined with exclusive enteral nutrition subgroup (ADA+EEN) and an adalimumab combined with partial nutrition subgroup (ADA+PEN) according to enteral nutrition intake. The changes in fecal calprotectin, CRP, Alb, Hb, Plt, ESR and CDAI, SES-CD and BMI were compared between the ADA+EEN group and the ADA+PEN group at week 0 (W0) and treatment outcomes at week 12(W12). The differences between the two groups before and after treatment were evaluated. To evaluate the effectiveness of the two treatments on patients' quality of life, nutritional recovery and body composition, patients in the ADA+EN group were needed to complete the Inflammatory Bowel Disease Questionnaire (IBDQ), EQ-5D-5L, the EuroQol visual analogue scale (EQ-VAS) and body composition analysis.A total of 28 patients completed all questionnaires and body composition analyses at week 0 and week 12, including 10 patients in the ADA+EEN group and 18 patients in the ADA+PEN group, respectively. The differences of in IBDQ, EQ-5D-5L and body composition analysis were compared between the two groups at week 0 (W0) and treatment outcomes at week 12(W12). Additionally, the differences between the two groups before and after treatment were evaluated. Results: These investigated indexes such as calprotectin, Hb, Plt, ESR, Alb, BMI, CRP, CDAI and SES-CD scores were significantly different before and after treatment in the ADA+EN group (p < 0.01). However, fecal calprotectin, Hb, SES-CD scores and Alb in the ADA group were not statistically significantly different from W0 to W12 (p > 0.05). The fecal calprotectin and CDAI scores in the ADA+EN group were significantly lower than those in the ADA group after treatment. The differences in all factors before and after treatment between the ADA+PEN group and the ADA+EEN group were statistically significant (p < 0.05). However, there was no significant difference between the two groups at week 12 (p > 0.05). Conclusion: Adalimumab combined with EN are more effective than ADA monotherapy in terms of endoscopy and clinical remission. By comparing the investigated indicators such as calprotectin, Hb, Plt, ESR ,CRP and SES-CD scores, it was proven that adalimumab combined with partial enteral nutrition or exclusive enteral nutrition has the same remission effect in induced Crohn's disease. The combination of biological agents and partial nutrition can improve medical order compliance, psychological burden and quality of life. Therefore, adalimumab combined with partial nutrition can be used as the first-line treatment for CD induced remission. [ABSTRACT FROM AUTHOR]

Exclusive enteral nutrition (EEN) is an established dietary treatment for Crohn's disease (CD) by alleviating inflammation and inducing remission. However, the mechanisms of action of EEN are incompletely understood. As CD is associated with gut microbiome dysbiosis, we investigated the effect of EEN on the microbiome in a rat model of CD-like colitis. The rat model of CD-like colitis was established by an intracolonic instillation of TNBS at 65 mg/kg in 250 µL of 40% ethanol. Sham control rats were instilled with saline. Rats were fed ad libitum with either regular pellet food or EEN treatment with a clear liquid diet (Ensure). Rats were euthanized at 7 days. Fecal pellets were collected from the distal colon for 16S rRNA sequencing analysis of gut microbiota. In addition, colon tissues were taken for histological and molecular analyses in all the groups of rats. EEN administration to TNBS-induced CD rats significantly improved the body weight change, inflammation scores, and disease activity index. The mRNA expression of IL-17A and interferon-γ was significantly increased in the colonic tissue in TNBS rats when fed with regular food. However, EEN treatment significantly attenuated the increase in IL-17A and interferon-γ in TNBS rats. Our 16S rRNA sequencing analysis found that gut microbiota diversity and compositions were significantly altered in TNBS rats, compared to controls. However, EEN treatment improved alpha diversity and increased certain beneficial bacteria such as Lactobacillus and Dubosiella and decreased bacteria such as Bacteroides and Enterorhabdus in CD-like rats, compared to CD-like rats with the regular pellet diet. In conclusion, EEN treatment increases the diversity of gut microbiota and the composition of certain beneficial bacteria. These effects may contribute to the reduced inflammation by EEN in the rat model of CD-like colitis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: A significant body of literature has interrogated the critical role of diet in the development and management of inflammatory bowel disease (IBD). Summary: This review provides a summary and critical appraisal of the literature in this area, focussing on four distinct themes: nutritional epidemiology, animal and in vitro experiments, enteral nutrition, and food-based dietary therapies. Key Messages: Nutritional epidemiology and data from experiments in animals indicate that a western-type diet pattern is associated with increased risk of IBD onset. However, these findings have not been consistently replicated in the dietary management of IBD. Exclusive enteral nutrition (EEN) is the only dietary therapy with reproducible evidence of efficacy in the management of active Crohn's disease (CD). Use of EEN may also be useful for improving perioperative outcomes in CD, and as an adjuvant therapy to biologic therapy. Several dietary therapies for CD and ulcerative colitis have been proposed in the literature, but replication in well-controlled studies is needed before their routine use enters the clinical setting. Precision nutritional therapy might be an attractive therapeutic paradigm in a heterogenous disease like IBD. However, no recommendations for personalised dietary therapy can currently be made, and it is imperative we unravel the complex interplay between diet and gut inflammation before we are able to do so. Undoubtedly, diet is of critical importance in the development and management of IBD. However, the exact mechanism by which diet causes gut inflammation is still elusive, and dietary guidance is difficult to formulate. [ABSTRACT FROM AUTHOR]

Background: Partial enteral nutrition (PEN) coupled with the Crohn's disease (CD) exclusion diet (CDED) was shown to be effective in inducing clinical remission in paediatric CD. There are currently no robust data on the endoscopic outcomes of PEN. The aim of this study was to evaluate the clinical and endoscopic rates of remission after PEN combined with a modified CDED (mCDED) adjusted to the local cuisine in comparison with exclusive enteral nutrition (EEN) for the induction of remission. Methods: Between June 2017 and February 2021, a prospective cohort study on children with active CD, treated with PEN + mCDED or EEN, was performed at a single tertiary centre. Results: During the study period, 54 patients were screened and 15 were excluded according to the exclusion criteria, with six patients excluded in the first two days due to intolerance of the enteral formula. Fourteen patients were included in the PEN and 19 in the EEN group. They were assessed at Weeks 0, 1, 3 and 6, using clinical and laboratory parameters. Endoscopy was performed at Weeks 0 and 6. Clinical remission rates per protocol analysis were 84.6% in the PEN group and 81.3% in the EEN group (p = 0.99). At Week 6, an endoscopic response (a decline in the Simple Endoscopic Score for CD (SES-CD) > 50%) was observed in 84.6% of patients on PEN and in 68.8% on EEN treatment (p = 0.41). Endoscopic remission (SES-CD ≤ 2) was achieved in 53.8% of patients in the PEN group and in 50.0% in the EEN group (p = 0.99), while the mucosal healing rates (SES-CD = 0) were 38.5% with PEN and 43.8% with EEN (p = 0.99). A significant decline in the clinical and endoscopic activity scores was observed in both groups. Conclusion: Our study suggests that PEN + mCDED could be effective in inducing endoscopic remission and mucosal healing in active paediatric CD patients. Here, we present an analysis of the data from our cohort of patients and our real-world experience with PEN + mCDED. [ABSTRACT FROM AUTHOR]

Summary: Background: Exclusive enteral nutrition (EEN) is an important alternative strategy for patients with Crohn’s disease (CD), and during this process, microbiota alterations have been observed. However, the underlying mechanisms by which EEN reduces intestinal inflammation are currently unclear. Methods: The therapeutic potential of enteral nutrition (EN) was assessed using various mouse models. Fecal full-length 16S rDNA sequencing analysis and several CD metagenome datasets were used to identify the candidate therapeutic bacteria Faecalibaculum rodentium (F. rodentium). Whole genome sequencing of F. rodentium and widely-targeted metabolome analysis of the supernatant showed that EN-induced F. rodentium accumulation protected against colitis via histidine biosynthesis. Findings: The therapeutic potential of EN therapy was observed in both dextran sulfate sodium (DSS)-induced colitis and Il10−/− spontaneous colitis mouse models. Accumulation of F. rodentium after EN therapy was determined using full-length 16S rDNA sequencing and verified with several metagenome datasets from patients with CD. Colonization of an isolated F. rodentium could reduce colitis in Il10−/− mice. Significant histidine enrichment was observed in the F. rodentium culture supernatant, and a series of histidine biosynthesis genes were observed in the F. rodentium genome. Engineered Escherichia coli Nissle 1917 (EcN), encoding the heterologous hisG of F. rodentium (EcN-hisG), which was a key driver of histidine biosynthesis in F. rodentium, was found to protect against colitis. Interpretation: This study suggests that EN-induced F. rodentium accumulation protects against colitis in mice via gut bacteria-mediated histidine biosynthesis. Funding: A full list of funding bodies can be found in the Acknowledgements section.

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 and Aims Treatment adherence is key to the efficacy of exclusive enteral nutrition [100% EN] in active Crohn's disease [CD], but there are no biomarkers to objectively estimate this. We explored faecal parameters as biomarkers of compliance with 100% EN, and subsequently developed and validated the Glasgow Exclusive Enteral Nutrition Index of Compliance [GENIE]. Methods Healthy adults replaced all [100% EN] or part [85% EN, 50% EN, 20% EN] of their diet with a formula for 7 days. Faecal pH, water content, short chain fatty acids, and branched chain fatty acids [BCFAs] were measured before [D0] and after [D7] each intervention. Optimal biomarkers and threshold values were derived using receiver operating characteristic curve analyses and machine learning to develop the GENIE. The GENIE was then validated in 30 CD children, during and after 100% EN. Results In all, 61 adults were recruited. D7 faecal pH and the ratios of BCFAs to either acetate or butyrate performed the best to differentiate between patients on 100% EN from <100% EN. Two models were generated; one included faecal metabolites (Laboratory GENIE, L-GENIE; sensitivity, specificity, and positive predictive value [PPV] of 88%, 94%, and 92%) and a second one [Clinical Genie, C-GENIE] which considers only faecal pH [sensitivity, specificity, and PPV of 84%, 86%, and 81%]. Validation of GENIE in CD children found that C-GENIE outperformed L-GENIE, producing a sensitivity, specificity, and PPV of 85%, 88%, and 88%, respectively. Conclusions GENIE can help predict adherence to 100% EN and may complement current conventional dietary assessment. [ABSTRACT FROM AUTHOR]

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.

Background: Exclusive enteral nutrition (EEN) is a highly effective therapy for remission induction in pediatric Crohn's disease (CD), but relapse rates after return to a regular diet are high. Autologous fecal microbiota transfer (FMT) using stool collected during EEN-induced clinical remission might represent a novel approach to maintaining the benefits of EEN. Methods: Pediatric CD patients provided fecal material at home, which was shipped at 4 °C to an FMT laboratory for FMT capsule generation and extensive pathogen safety screening. The microbial community composition of samples taken before and after shipment and after encapsulation was characterized using 16S rRNA amplicon sequencing. Results: Seven pediatric patients provided fecal material for nine test runs after at least three weeks of nutritional therapy. FMT capsules were successfully generated in 6/8 deliveries, but stool weight and consistency varied widely. Transport and processing of fecal material into FMT capsules did not fundamentally change microbial composition, but microbial richness was <30 genera in 3/9 samples. Stool safety screening was positive for potential pathogens or drug resistance genes in 8/9 test runs. Conclusions: A high pathogen burden, low-diversity microbiota, and practical deficiencies of EEN-conditioned fecal material might render autologous capsule-FMT an unsuitable approach as maintenance therapy for pediatric CD patients. [ABSTRACT FROM AUTHOR]

Gut dysbiosis and associated bile acid (BA) metabolism play an important role in the pathogenesis of Crohn's disease (CD). We investigated the impacts of the exclusive enteral nutrition treatment (EEN) on the gut microbiome (GM) and BAs metabolism for patients with CD. Targeted metabolomics analysis and metagenomics analysis were performed in feces to investigate the BA and GM changes of patients before and after 2-months EEN therapy. The Pediatric Crohn's Disease Activity Index (PCDAI) and fecal calprotectin were used to evaluate the severity and mucosal inflammation of CD. A total of 27 newly diagnosed pediatric patients with CD and 27 healthy controls were recruited in this study. Both GM structure and the secondary BA metabolism were significantly impaired in patients, which could return towards normal levels after EEN treatment. The most abundant taxa Firmicutes and 11 BAs were found closely associated with the PCDAI score and fecal calprotectin. Meanwhile, the close interactions between Firmicute bacteria and BAs might contribute to the remission of CD after EEN treatment. The qPCR data further confirmed that the relative expressions of Firmicutes phylum, and genus Flavonifractor and Clostridium V were improved after EEN treatment. Firmicutes bacteria and the balance of primary and secondary BA compositions in the gut were closely associated with the health status of CD disease indicated by the PCDAI score and fecal calprotectin. Understanding the recovery process of gut microbiome and BA metabolism will help us to explore the potential mechanisms of EEN therapy. [ABSTRACT FROM AUTHOR]

This study aims to determine changes in the intestinal microbiota of children with Crohn's disease (CD) before and during exclusive enteral nutrition (EEN) and after its discontinuation. A total of 14 newly diagnosed children with CD (median age 16.0 years; 43% female) were included in this study. Patients were initially treated with EEN and were followed for one year after EEN discontinuation. Stool samples were taken at the time of diagnosis (before EEN introduction), the second day of EEN, the last day of EEN, and every two months for one year after the discontinuation of EEN. A molecular approach targeting 16S ribosomal RNA was used for analysing the gut microbiota. No change was found in the Shannon diversity index before, during, and after EEN cessation (HhaI-digestion p = 0.82; MspI-digestion p = 0.87). According to the PCO, on the basis of the dissimilarity matrices of OTUs, a clear separation of patients at different time points, forming two clusters (before and during EEN as opposed to after EEN), was evident. No clear separation was noted between patients who achieved sustained remission as opposed to those who did not achieve sustained remission during EEN and at the follow-up. In conclusion, a distinct change in the microbiota composition already occurred after two months of EEN discontinuation and remained mostly unchanged over a year of follow-up. [ABSTRACT FROM AUTHOR]

Inflammatory Bowel Disease (IBD) includes a spectrum of chronic immune-mediated intestinal diseases thought to be related to the complex interaction between the host immune system and the intestinal microbiome. Research supports the use of nutritional therapy in IBD; however, it is not routinely used in clinical practice. This literature review seeks to advance the understanding of diet and its effect in IBD with a focus on both Crohn's Disease (CD) and Ulcerative Colitis (UC). The contribution of diet to the development and treatment of IBD cannot be overstated. In both pediatric as well as adult IBD, nutritional interventions have been shown to improve clinical symptoms as well as inflammatory burden. The impact of dietary intervention is best exemplified through the use of Exclusive Enteral Nutrition (EEN) in CD. EEN and clinical research on exclusionary whole food diets—Crohn's Disease Exclusion Diet (CDED), Specific Carbohydrate Diet (SCD), low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet, and Mediterranean Diet—are discussed within this review. Current clinical literature supports the elimination of detrimental components and the incorporation of low processed whole foods in the diet. Additional prospective and longitudinal dietary studies on sustainable and long-term dietary options, along with a deeper understanding of the mechanism, are needed to further advance the role of nutritional interventions in IBD. [ABSTRACT FROM AUTHOR]

Short-chain polypeptides are composed of three to nine amino acids, which can be absorbed by the intestinal tract without digestive enzymes and ATP energy. Crohn’s disease (CD) is a chronic non-specific disease derived from inflammation and damage of the gastrointestinal tract. In this study, we aim to investigate the effect of short-chain polypeptide-based exclusive enteral nutrition (EEN) formulas on intestinal injury in Chinese children with active CD. From January 2013 to January 2019, a total of 84 consecutive children with a diagnosis of Crohn’s disease (CD) in the Department of Pediatric Gastroenterology, Children’s Hospital of Nanjing Medical University, were divided into mild and moderate-to-severe active CD groups. Each group was further divided into two subgroups: drug group and short-chain polypeptide plus drug group. Tests were carried out on the levels of intestinal fatty acid binding protein (I-FABP) in the blood, fecal calprotectin (FC), and occludin protein in the intestinal mucosa 1 day before treatment and 8 weeks after treatment. Endoscopic and histopathological observations were detected to compare the changes in intestinal injury in children with active CD. After 8 weeks of treatment, the SES-CD scores and Chiu scores of the ileocecal area and terminal ileum of children with mild active CD and the ileocecal area of children with moderate-to-severe active CD in short-chain polypeptide plus drug group were significantly lower than those in the drug group. The OD value of occludin in the terminal ileum and ileocecal area of children with mild active CD and the ileocecal area of children with moderate-to-severe active CD after short-chain polypeptide-based EEN formulas and drug treatment was significantly higher than those in the drug group (p

Exclusive enteral nutrition (EEN) is an established dietary treatment for Crohn’s disease (CD) by alleviating inflammation and inducing remission. However, the mechanisms of action of EEN are incompletely understood. As CD is associated with gut microbiome dysbiosis, we investigated the effect of EEN on the microbiome in a rat model of CD-like colitis. The rat model of CD-like colitis was established by an intracolonic instillation of TNBS at 65 mg/kg in 250 µL of 40% ethanol. Sham control rats were instilled with saline. Rats were fed ad libitum with either regular pellet food or EEN treatment with a clear liquid diet (Ensure). Rats were euthanized at 7 days. Fecal pellets were collected from the distal colon for 16S rRNA sequencing analysis of gut microbiota. In addition, colon tissues were taken for histological and molecular analyses in all the groups of rats. EEN administration to TNBS-induced CD rats significantly improved the body weight change, inflammation scores, and disease activity index. The mRNA expression of IL-17A and interferon-γ was significantly increased in the colonic tissue in TNBS rats when fed with regular food. However, EEN treatment significantly attenuated the increase in IL-17A and interferon-γ in TNBS rats. Our 16S rRNA sequencing analysis found that gut microbiota diversity and compositions were significantly altered in TNBS rats, compared to controls. However, EEN treatment improved alpha diversity and increased certain beneficial bacteria such as Lactobacillus and Dubosiella and decreased bacteria such as Bacteroides and Enterorhabdus in CD-like rats, compared to CD-like rats with the regular pellet diet. In conclusion, EEN treatment increases the diversity of gut microbiota and the composition of certain beneficial bacteria. These effects may contribute to the reduced inflammation by EEN in the rat model of CD-like colitis.

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.

Background: Partial enteral nutrition (PEN) coupled with the Crohn’s disease (CD) exclusion diet (CDED) was shown to be effective in inducing clinical remission in paediatric CD. There are currently no robust data on the endoscopic outcomes of PEN. The aim of this study was to evaluate the clinical and endoscopic rates of remission after PEN combined with a modified CDED (mCDED) adjusted to the local cuisine in comparison with exclusive enteral nutrition (EEN) for the induction of remission. Methods: Between June 2017 and February 2021, a prospective cohort study on children with active CD, treated with PEN + mCDED or EEN, was performed at a single tertiary centre. Results: During the study period, 54 patients were screened and 15 were excluded according to the exclusion criteria, with six patients excluded in the first two days due to intolerance of the enteral formula. Fourteen patients were included in the PEN and 19 in the EEN group. They were assessed at Weeks 0, 1, 3 and 6, using clinical and laboratory parameters. Endoscopy was performed at Weeks 0 and 6. Clinical remission rates per protocol analysis were 84.6% in the PEN group and 81.3% in the EEN group (p = 0.99). At Week 6, an endoscopic response (a decline in the Simple Endoscopic Score for CD (SES-CD) > 50%) was observed in 84.6% of patients on PEN and in 68.8% on EEN treatment (p = 0.41). Endoscopic remission (SES-CD ≤ 2) was achieved in 53.8% of patients in the PEN group and in 50.0% in the EEN group (p = 0.99), while the mucosal healing rates (SES-CD = 0) were 38.5% with PEN and 43.8% with EEN (p = 0.99). A significant decline in the clinical and endoscopic activity scores was observed in both groups. Conclusion: Our study suggests that PEN + mCDED could be effective in inducing endoscopic remission and mucosal healing in active paediatric CD patients. Here, we present an analysis of the data from our cohort of patients and our real-world experience with PEN + mCDED.

Background and aims: Exclusive enteral nutrition is recommended as a first-line treatment in active pediatric Crohn's Disease, but its mechanism of action is still not clear. We aimed to assess alterations in the metabolic profile of newly diagnosed pediatric Crohn's Disease patients before and during exclusive enteral nutrition therapy. Methods: Plasma samples from 14 pediatric Crohn's Disease patients before and after 3–4 weeks on exclusive enteral nutrition were analyzed using mass spectrometry. T-test, fold change and orthogonal partial least squares discriminant analysis were used for mining significant features. Correlation analysis was performed between the annotated features and the weighted pediatric Crohn's disease activity index using Pearson r distance. Results: Among the 13 compounds which decreased during exclusive enteral nutrition, most are related to diet, while one is a bacterial metabolite, Bacteriohopane-32,33,34,35-tetrol. The phosphatidic acid metabolite PA(15:1/18:0) was significantly reduced and correlated with the weighted pediatric Crohn's disease activity index. Lipids increased during exclusive enteral nutrition therapy included phosphatidylethanolamines; PE(24:1/24:1), PE(17:2/20:2) and one lactosylceramide; LacCer(d18:1/14:0). Conclusion: Food additives and other phytochemicals were the major metabolites, which decreased following the exclusion of a regular diet during exclusive enteral nutrition. An alteration in bacterial biomarkers may reflect changes in intestinal microbiota composition and metabolism. Thus, metabolomics provides an opportunity to characterize the molecular mechanisms of dietary factors triggering Crohn's Disease activity, and the mechanisms of action of exclusive enteral nutrition, thereby providing the basis for the development and evaluation of improved intervention strategies for prevention and treatment. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease has become a global health problem at the turn of the 21st century. The pathogenesis of this disorder has not been fully explained. In addition to non-modifiable genetic factors, a number of modifiable factors such as diet or gut microbiota have been identified. In this paper, the authors focus on the role of nutrition in the prevention of inflammatory bowel disease as well as on the available options to induce disease remission by means of dietary interventions such as exclusive and partial enteral nutrition in Crohn's disease, the efficacy of which is reported to be comparable to that of steroid therapy. Diet is also important in patients with inflammatory bowel disease in the remission stage, during which some patients report irritable bowel disease-like symptoms. In these patients, the effectiveness of diets restricting the intake of oligo-, di-, monosaccharides, and polyols is reported. [ABSTRACT FROM AUTHOR]

Abstract Background Although there are many hypotheses, the pathogenesis of Crohn's disease (CD) is not completely clear so far. Exclusive enteral nutrition (EEN) is a routine measure in the treatment of active CD. We aimed at investigating the impact of EEN on patients with active CD from microbial metabolomics. Methods 16S-rDNA sequencing technology and gas chromatography–mass spectrometer analysis were employed to investigate the modification of the intestinal flora and fecal short-chain fatty acid (SCFA) during the EEN. Results Seven patients with CD, who conducted EEN, were followed up successfully in the present study. The 8-week EEN resulted in a remission of the condition of subjects with active CD, as revealed by a significant decrease in erythrocyte sedimentation rate (ESR) (P = 0.018), C-reactive protein (CRP) (P = 0.028), and Crohn’s disease activity index (CDAI) (P = 0.018). The nutrition of the subjects was improved after an 8-week treatment course with EEN, which was associated with an increase in body mess index (BMI) (P = 0.018) and serum albumin (ALB) (P = 0.018) levels. Furthermore, our investigations revealed a significantly increased abundance of Firmicutes paralleled by decreased levels of Proteobacteria. With respect to the genus, five species of bacteria including Ruminococcus (P = 0.01), Lachnospiraceae (P = 0.02), Anaerotruncus (P = 0.04), Flavonifractor (P = 0.04), and Novosphingobium (P = 0.05) showed significantly increased abundance. This was accompanied by relative changes in fecal short-chain fatty acids levels. Moreover, we successfully constructed a stable model by combining these five significantly different genera to predict the therapeutic effect of EEN on patients with CD (AUC = 0.9598). Conclusions The findings indicated that EEN can alleviate the condition and the nutrition of patients with active CD by regulating the intestinal flora and influencing the expression level of fecal short-chain fatty acids.

Abstract Background and Aim Data on factors influencing time to remission in pediatric Crohn's disease (CD) are very limited in the literature. The aim of this retrospective cohort study was to describe the trends of time to clinical remission over the past decade and to identify factors associated with time to clinical remission in children with luminal CD. Methods Patients under 18 years old diagnosed between 2009 and 2019 were included. All data were collected from the patients' medical records. Survival analyses and linear regression models were used to assess the impact of clinical, laboratory, endoscopic, histological, and therapeutic factors on time to clinical remission. Results A total of 654 patients were included in the study. There was no change in the time to clinical remission over the decade. Female sex in adolescents (adjusted bêta regression coefficient [aβ] = 31.8 days, P = 0.02), upper digestive tract involvement (aβ = 46.4 days, P = 0.04) perianal disease (aβ = 32.2 days, P = 0.04), presence of active inflammation on biopsies at diagnosis (aβ = 46.7 days, P = 0.01) and oral 5‐aminosalicylates (5‐ASA) exposure (aβ = 56.6 days, P = 0.002) were associated with longer time to clinical remission. Antibiotic exposure (aβ = −29.3 days, P = 0.04), increased eosinophils (aβ = −29.6 days, P = 0.008) and combination of exclusive enteral nutrition with tumor‐necrosis‐factor‐alpha (TNF‐alpha) inhibitors as induction therapy (aβ = −36.8 days, P = 0.04) were associated with shorter time to clinical remission. Conclusion In children with newly diagnosed Crohn's disease, time to clinical remission did not shorten during the decade. It was associated with baseline clinical and histological data and treatment strategies. Combination of enteral nutrition and TNF‐alpha inhibitors was associated with faster clinical remission.

Roberto de Sire, Olga Maria Nardone, Anna Testa, Giulio Calabrese, Anna Caiazzo, Fabiana Castiglione Department of Clinical Medicine and Surgery, University Federico II of Naples, Naples, ItalyCorrespondence: Fabiana CastiglioneDepartment of Clinical Medicine and Surgery, University Federico II of Naples, Via S. Pansini 5, Naples, 80131, ItalyEmail fabcasti@unina.itAbstract: Recently, the role of nutrition in the management of Crohn’s disease (CD) is of increasing interest and the exploration of novel nutritional interventions to improve long-term management of the disease is challenging. So far, the majority of the studies on the role of exclusive enteral nutrition (EEN) in CD are conducted in the pediatric population and have highlighted the efficacy of EEN for achieving mucosal healing. This implicates that a similar approach would be beneficial in adult patients. However, the evidence for EEN in adults is heterogeneous, with meta-analyses reporting it as inferior to steroids while growing data demonstrate improvement in complicated CD. Currently, EEN is less used in adult patients with IBD. Indeed, the lack of palatability of enteral formula leads to difficulties in acceptance and compliance. The search for more tolerable and still effective diets has become an intense area of research aiming to explore the potential role of diet to control inflammation in patients with CD. Thus, this narrative review provides the state-of-the-art on the use of EEN treatment in CD and highlights the perceived barriers to its implementation in adult CD patients.Keywords: Crohn’s disease, exclusive enteral nutrition, barriers, diet, nutritional interventions

Sohouli and colleagues concluded that EEN can provide important beneficial effects on CD activity, inflammatory markers, and growth factors. 8 Werkstetter KJ, Schatz SB, Alberer M, Filipiak-Pittroff B, Koletzko S. Influence of exclusive enteral nutrition therapy on bone density and geometry in newly diagnosed pediatric Crohn's disease patients. It has been touted as an effective therapy for active Crohn's disease (CD), particularly in children, perhaps because potential antigens in food have been removed.[1] To assess the effects of EEN, Sohouli and five Iranian colleagues undertook a systematic review. Keywords: control groups; Crohn's disease; exclusive enteral nutrition; gastroenterology; heterogeneity; measurements; pediatrics; regression to the mean; risk of bias; systematic review EN control groups Crohn's disease exclusive enteral nutrition gastroenterology heterogeneity measurements pediatrics regression to the mean risk of bias systematic review 686 688 3 07/07/23 20230701 NES 230701 Exclusive enteral nutrition (EEN) is an intervention in which patients do not eat solid food but only consume liquid diets (usually commercial formulations) for a number of weeks. [Extracted from the article]

Summary: Background: There is evidence of inconsistency in sequelae of exclusive enteral nutrition (EEN) as induction therapy in paediatric patients with Crohn's disease (CD). Aim: To investigate the potential effects of EEN on paediatric Crohn's disease activity index (PCDAI), inflammation and biochemical parameters in paediatric patients with CD. Methods: We performed a comprehensive systematic search of PubMed/MEDLINE, Web of Science, SCOPUS and Embase until 8 January 2022 regardless of the time of publication or language. Random‐effects model was applied to combine the datasets. The main outcomes were analysed through mean difference (MD) and its 95% confidence interval (CI). Results: Forty six studies met eligibility criteria and were included in the meta‐analysis. Pooled findings indicated that PCDAI score (MD of −27.24; 95% CI −31.84 to −22.64), calprotectin (MD of −842.83 mg/kg; CI −1018.24 to −667.42), CRP (pooled MD of −2.36 mg/dl; CI −2.68 to −2.03), and ESR (MD of −21.09 mm/h; CI −23.79 to −18.38), albumin (MD of 0.65 g/dl; CI 0.58 to 0.72), haemoglobin (MD of 1.12 g/dl; CI 0.87 to 1.37), weight (MD of 4.30 kg; CI 3.39 to 5.22), and height (MD of 0.98 cm; CI 0.35 to 1.62) improved significantly with EEN. Conclusions: Adherence to EEN can have significant, beneficial effects as induction therapy in paediatric patients with CD. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the clinical efficacy of short-peptide exclusive enteral nutrition (EEN) therapy in inducing remission during active Crohn's disease (CD) in children, as well as changes in physical growth and nutritional indicators before and after treatment., Methods: A prospective study included 43 children with active CD who were admitted to the Department of Gastroenterology, Children's Hospital of Nanjing Medical University from January 2017 to January 2024. The participants were randomly divided into a medication treatment group (13 children) and a short-peptide + medication treatment group (30 children). The changes in the Pediatric Crohn's Disease Activity Index (PCDAI) scores, physical growth, and nutritional indicators before and after treatment were analyzed in both groups., Results: The PCDAI scores in the short-peptide + medication treatment group were lower than those in the medication treatment group after treatment ( P <0.05). The Z-scores for weight-for-age, body mass index, and albumin levels were higher in the short-peptide + medication treatment group compared to the medication treatment group ( P <0.05). In the patients with moderate to severe CD, total protein levels in the short-peptide + medication treatment group were significantly higher than those in the medication treatment group ( P <0.05)., Conclusions: Short-peptide EEN therapy can induce clinical remission in children with active CD and promote their physical growth while improving their nutritional status.

Background: Mesenteric adipose tissue (mAT) hyperplasia, known as creeping fat, is a pathologic characteristic of Crohn's disease (CD). In our previously reported cohort, we observed that Achromobacter pulmonis was the most abundant and prevalent bacteria cultivated from creeping fat., Methods: A whole genomic sequencing and identification of T3SS orthologs of mAT-derived A. pulmonis were used. A functional type III secretion system (T3SS) mediated the pathogenic potential of A. pulmonis in vitro and in mouse colitis model. Furthermore, a T3SS Finder pipeline was introduced to evaluate gut bacterial T3SS orthologs in the feces of CD patients, ulcerative colitis and colorectal cancer patients., Findings: Here, we reveal that mAT-derived A. pulmonis possesses a functional T3SS, aggravates colitis in mice via T3SS, and exhibits T3SS-dependent cytotoxicity via a caspase-independent mechanism in macrophages and epithelial cells, which demonstrated the pathogenic potential of the T3SS-harboring A. pulmonis. Metagenomic analyses demonstrate an increased abundance of Achromobacter in the fecal of Crohn's disease patients compared to healthy controls. A comprehensive comparison of total microbial vT3SS abundance in various intestine diseases demonstrated that the specific enrichment of vT3SS genes was shown in fecal samples of CD, neither ulcerative colitis nor colorectal cancer patients, and ten T3SS gene-based biomarkers for CD were discovered and validated in a newly recruited CD cohort. Furthermore, treatment with exclusive enteral nutrition (EEN), an intervention that improves CD patient symptomatology, was found associated with a significant reduction in the prevalence of T3SS genes in fecal samples., Interpretation: These findings highlight the pathogenic significance of T3SSs in the context of CD and identify specific T3SS genes that could potentially function as biomarkers for diagnosing and monitoring the clinical status of CD patients., Funding: This work is supported by the National Key Research and Development Program of China (2020YFA0907800), the China Postdoctoral Science Foundation (2023M744089), the National Natural Science Foundation of China (32000096), the Shenzhen Science and Technology Programs (KQTD20200820145822023, RCIC20231211085944057, and ZDSYS20220606100803007), National Key Clinical Discipline, Guangdong Provincial Clinical Research Center for Digestive Diseases (2020B1111170004), Qingfeng Scientific Research Fund of the China Crohn's & Colitis Foundation (CCCF) (CCCF-QF-2022B71-1), and the Sixth Affiliated Hospital, Sun Yat-sen University Clinical Research 1010 Program 1010CG(2023)-08. These funding provided well support for this research work, which involved data collection, analysis, interpretation, patient recruitment and so on., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Exclusive enteral nutrition (EEN) is the recommended first-line induction treatment in pediatric patients with active luminal Crohn's disease (CD). We aimed to provide a nationwide overview of evolving EEN practices during an era of increasing biologic use., Methods: We analyzed a prospectively identified nationwide cohort of newly diagnosed pediatric patients with CD in Scotland between January 1, 2015, and June 30, 2022. Patients who received EEN for any indication were divided into 6-monthly epochs and examined over time. Differences during the COVID-19 pandemic (March 16, 2020, to July 19, 2021) were examined. Data were retrospectively collected from electronic medical records: demographics, anthropometrics, concomitant treatments, aspects of EEN administration, and remission/response rates. Descriptive statistics and linear regression were used for analyses., Results: A total of 649 patients with CD were identified (63% male; median age 12.6 [interquartile range, 10.8-14.8] years); 497 (77%) of 649 received EEN as postdiagnosis induction therapy with a median course length of 7.7 (interquartile range, 5.9-8.0) weeks. Including repeat courses, 547 EEN courses were examined. An increasing incidence of CD was observed over time with no significant changes in EEN usage, remission or response rates, nasogastric tube usage, or course completion (all P > .05). Increasing use of EEN combined with biologics (combination induction) as first-line induction was observed over time (P < .001). Considering COVID-19, lower rates of EEN usage were observed (P = .008) with no differences in remission, oral administration, and course completion rates (all P > .05)., Conclusions: Over the past 7.5 years, except during the COVID-19 pandemic, EEN usage rates have not changed despite an increase in biologic use, although combination induction is an emerging trend., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Shuyan Li,1,&ast; Peiwei Li,2,&ast; Hongling Sun,1 Wen Hu,3 Shurong Hu,2 Yan Chen,2 Minfang Lv2 1Department of Nursing, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, People’s Republic of China; 2Center for Inflammatory Bowel Diseases, Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, People’s Republic of China; 3State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Minfang Lv; Yan ChenCenter for Inflammatory Bowel Diseases, Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, People’s Republic of ChinaTel/Fax +86-571-87783540; +86-571-87783936Email ZRLMF@zju.edu.cn; chenyan72_72@zju.edu.cnBackground: The prevalence of Crohn’s disease (CD) has been increasing rapidly in China, and the role of exclusive enteral nutrition (EEN) in the management of adult patients with active CD is evolving. Adherence is a key factor in the effective treatment of many chronic diseases.Aim: The aim of this study was to assess adherence to EEN of CD patients and to evaluate the relationship between medication belief and EEN adherence.Methods: A cross-sectional study was conducted, and demographic information, adherence to EEN, and beliefs about EEN were investigated. Medication belief was measured using the Beliefs about Medicines Questionnaire (BMQ)-Specific.Results: In all, 131 CD patients completed the questionnaire and were enrolled in this study. The high adherence rate was 73.3% (96 of 131 patients), and we found that medication belief, residency, medical insurance, and history of enteral nutrition therapy were factors affecting EEN adherence. More patients with a high BMQ score had high adherence to EEN (n = 54, 56.2%) compared to those with a low BMQ (n = 42, 43.8%). Moreover, price, taste, storage method, portability, and purchase convenience of EEN were not associated with adherence.Conclusion: The adherence to EEN among patients with CD is relatively high and is related to medication belief, residency and history of enteral nutrition. The type of enteral nutrition, taste, storage, and convenience of purchase were not associated with EEN adherence. Future study is warranted to explore the possible role of improving patients’ beliefs in increasing adherence.Keywords: exclusive enteral nutrition, adherence, Crohn’s disease

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Background: Although there are many hypotheses, the pathogenesis of Crohn's disease (CD) is not completely clear so far. Exclusive enteral nutrition (EEN) is a routine measure in the treatment of active CD. We aimed at investigating the impact of EEN on patients with active CD from microbial metabolomics.Methods: 16S-rDNA sequencing technology and gas chromatography-mass spectrometer analysis were employed to investigate the modification of the intestinal flora and fecal short-chain fatty acid (SCFA) during the EEN.Results: Seven patients with CD, who conducted EEN, were followed up successfully in the present study. The 8-week EEN resulted in a remission of the condition of subjects with active CD, as revealed by a significant decrease in erythrocyte sedimentation rate (ESR) (P = 0.018), C-reactive protein (CRP) (P = 0.028), and Crohn's disease activity index (CDAI) (P = 0.018). The nutrition of the subjects was improved after an 8-week treatment course with EEN, which was associated with an increase in body mess index (BMI) (P = 0.018) and serum albumin (ALB) (P = 0.018) levels. Furthermore, our investigations revealed a significantly increased abundance of Firmicutes paralleled by decreased levels of Proteobacteria. With respect to the genus, five species of bacteria including Ruminococcus (P = 0.01), Lachnospiraceae (P = 0.02), Anaerotruncus (P = 0.04), Flavonifractor (P = 0.04), and Novosphingobium (P = 0.05) showed significantly increased abundance. This was accompanied by relative changes in fecal short-chain fatty acids levels. Moreover, we successfully constructed a stable model by combining these five significantly different genera to predict the therapeutic effect of EEN on patients with CD (AUC = 0.9598).Conclusions: The findings indicated that EEN can alleviate the condition and the nutrition of patients with active CD by regulating the intestinal flora and influencing the expression level of fecal short-chain fatty acids. [ABSTRACT FROM AUTHOR]

Background/Aims Exclusive enteral nutrition (EEN), an established modality for pediatric Crohn’s disease (CD) is seldomly utilized in adults. The present study reports the outcome of EEN in adult CD patients at a tertiary care hospital in India. Methods This was a retrospective analysis of CD patients who received EEN as a sole modality/adjunct to other treatment. The primary and secondary outcomes changed in Crohn’s Disease Activity Index (CDAI), and clinical response (decline in CDAI > 70), respectively, at 4 and 8 weeks. Subgroup analysis evaluated response across different phenotypes, EEN formulations and prior treatment. Linear mixed effect model was created to assess the predictors of EEN response. Results Thirty-one CD patients received EEN over median duration of 4 weeks (range, 2–6 weeks). CDAI showed a significant improvement post EEN at 4 (baseline 290 [260–320] vs. 240 [180–280], P=0.001) and 8 weeks (baseline 290 [260–320] vs. 186 [160–240], P=0.001), respectively. The cumulative clinical response rates at 4 and 8 weeks were 37.3% and 80.4% respectively. The clinical response rates at 8 weeks across B1 (n = 4), B2 (n = 18) and B3 (n = 9) phenotypes were 50%, 78.8% and 100% respectively (log-rank test, P=0.093). The response rates at 8 weeks with polymeric (n = 8) and semi-elemental diet (n = 23) were 75% and 82.6%% respectively (log-rank test, P=0.49). Baseline CDAI (odds ratio, 1.008; 95% confidence interval, 1.002–1.017; P=0.046) predicted response to EEN. Conclusions EEN was effective in inducing clinical response across different phenotypes of CD. Baseline disease activity remained the most important predictor of clinical response to EEN.

Background: Exclusive enteral nutrition (EEN) is a highly effective therapy for remission induction in pediatric Crohn’s disease (CD), but relapse rates after return to a regular diet are high. Autologous fecal microbiota transfer (FMT) using stool collected during EEN-induced clinical remission might represent a novel approach to maintaining the benefits of EEN. Methods: Pediatric CD patients provided fecal material at home, which was shipped at 4 °C to an FMT laboratory for FMT capsule generation and extensive pathogen safety screening. The microbial community composition of samples taken before and after shipment and after encapsulation was characterized using 16S rRNA amplicon sequencing. Results: Seven pediatric patients provided fecal material for nine test runs after at least three weeks of nutritional therapy. FMT capsules were successfully generated in 6/8 deliveries, but stool weight and consistency varied widely. Transport and processing of fecal material into FMT capsules did not fundamentally change microbial composition, but microbial richness was

This study aims to determine changes in the intestinal microbiota of children with Crohn’s disease (CD) before and during exclusive enteral nutrition (EEN) and after its discontinuation. A total of 14 newly diagnosed children with CD (median age 16.0 years; 43% female) were included in this study. Patients were initially treated with EEN and were followed for one year after EEN discontinuation. Stool samples were taken at the time of diagnosis (before EEN introduction), the second day of EEN, the last day of EEN, and every two months for one year after the discontinuation of EEN. A molecular approach targeting 16S ribosomal RNA was used for analysing the gut microbiota. No change was found in the Shannon diversity index before, during, and after EEN cessation (HhaI-digestion p = 0.82; MspI-digestion p = 0.87). According to the PCO, on the basis of the dissimilarity matrices of OTUs, a clear separation of patients at different time points, forming two clusters (before and during EEN as opposed to after EEN), was evident. No clear separation was noted between patients who achieved sustained remission as opposed to those who did not achieve sustained remission during EEN and at the follow-up. In conclusion, a distinct change in the microbiota composition already occurred after two months of EEN discontinuation and remained mostly unchanged over a year of follow-up.

Background: Exclusive enteral nutrition (EEN) is the first-line therapy for pediatric-onset Crohn's disease (CD) patients. CEDATA-GPGE® is the largest patient registry for children and adolescents with inflammatory bowel disease (IBD) in Europe, collecting data from over 5000 patients since 2004 in Germany and Austria. Since the application of EEN over 8 weeks is difficult and a high dropout rate is often described, the mode of application including a supporting structure is crucial for success. The aim of this study was to ascertain the variation in the application of EEN across the participating centers and to associate these with the outcome. Results: Thirty-one centers responded to the survey (81.6%). 88.5% of CD patients were recommended EEN for induction therapy, 71.8% actually started with EEN, and 22.1% terminated the EEN prematurely. The duration of EEN typically lasted 6 to 8 weeks, and the polymeric formula was mainly used. 80.6% of the clinics added flavorings to the formulas. After EEN, the most preferred diet for maintenance therapy was a healthy, well-balanced diet considering individual intolerances. Conclusions: EEN is widely recommended as an induction therapy by the German and Austrian pediatric gastroenterologists for children and adolescents with CD. However, this questionnaire-based study has shown a wide variation in EEN protocols used by the different pediatric clinics of CEDATA-GPGE®. [ABSTRACT FROM AUTHOR]

Pediatric Crohn's disease (CD) is commonly associated with hepatobiliary complications, including transient liver enzymes elevation (LEE). Exclusive enteral nutrition (EEN) is recommended as primary treatment in mild-to-moderate pediatric CD. Data concerning EEN and liver enzymes (LE) abnormalities are limited. The aim of this study was to assess the LEE occurrence in newly diagnosed CD pediatric patients during EEN. Retrospective analysis of 73 patients, with no previous signs of liver disease, qualified to EEN. LE were assessed at diagnosis, during EEN, after completion of the nutritional treatment, and reintroduction of free diet. Thirty-one (42%) children presented with LEE and 28 (38%) with transient LEE. The LEE cohort presented with higher percentage of protein energy (24.0% ± 29.4 IQR [interquartile range] vs. 18.6% ± 23.6 IQR, P < .05) versus nonprotein energy (fat and carbohydrates) in total energy intake (75.9% ± 29.4 IQR vs. 81.4% ± 23.6 IQR, P < .05). Also, the protein/energy ratio was higher in the LEE group compared with the group with normal LE (0.026 vs. 0.024, P = .028). At the fourth week of EEN, aspartate aminotransferase elevation correlated with higher daily protein intake (P < .018). The LEE during EEN is typically a low-grade and transient condition that may be connected to applied treatment. We hypothesize that higher protein/energy ratio during EEN may be associated with mild, temporary LEE. Careful observation with repeated measurement of LE activity may be sufficient proceeding in patients without any other symptoms of CD-associated liver disease. [ABSTRACT FROM AUTHOR]