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ABSTRACT Gut dysbiosis is closely related to dysregulated microRNAs (miRNAs) in the intestinal epithelial cells, which plays an important role in the pathogenesis of Crohn’s disease (CD). We investigated the relationship between fecal gut microbiome (GM) and intestinal tissue miRNAs in different stages of pediatric CD. Metagenomic analysis and miRNA sequencing were conducted to examine the GM and intestinal miRNA profiles of CD patients before and after clinical induction therapy and the controls. Twenty-seven newly diagnosed, therapy-naïve pediatric patients with active CD and 11 non-inflammatory bowel disease (IBD) controls were recruited in this study. Among CD patients, 11 patients completed induction treatment and reached clinical remission. Both GM and miRNA profiles were significantly changed between CD patients and controls. Seven key bacteria were identified at species level including Defluviitalea raffinosedens, Thermotalea metallivorans, Roseburia intestinalis, Dorea sp. AGR2135, Escherichia coli, Shigella sonnei, and Salmonella enterica, the exact proportions of which were further validated by real-time quantitative PCR analysis. Eight key miRNAs were also identified including hsa-miR-215-5p, hsa-miR-194-5p, hsa-miR-12135, hsa-miR-509-3-5p, hsa-miR-212-5p, hsa-miR-4448, hsa-miR-501-3p, and hsa-miR-503-5p. The functional enrichment analysis of differential miRNAs indicated the significantly altered cyclin protein, cyclin-dependent protein, and cell cycle pathway. The close interactions between seven key bacteria and eight key miRNAs were further investigated by miRNA target prediction. The association between specific miRNA expressions and key gut bacteria at different stages of CD supported their important roles as potential molecular biomarkers. Understanding the relationship between them will help us to explore the molecular mechanisms of CD.IMPORTANCESince previous studies have focused on the change of the fecal gut microbiome and intestinal tissue miRNA in pediatric Crohn’s disease (CD), the relationship between them in different stages is still not clear. This is the first study to explore the gut microbiota and miRNA and their correlations with the Pediatric Crohn’s Disease Activity Index (PCDAI). Crohn’s Disease Endoscopic Index of Severity (CDEIS), and calprotectin, by applying two omics approach in three different groups (active CD, CD in remission with exclusive enteral nutrition or infliximab induction therapy, and the healthy controls). Both gut microbiome structure and the miRNA profiles were significantly changed in the different stage of CD. Seven key gut microbiome at species and eight key miRNAs were found, and their close interactions were further fully investigated by miRNA target prediction.

Background: The incidence of pediatric Crohn’s disease (PCD) is increasing worldwide every year. The challenges in early diagnosis and treatment of PCD persist due to its inherent heterogeneity. This study’s objective was to discover novel diagnostic markers and molecular subtypes aimed at enhancing the prognosis for patients suffering from PCD. Methods: Candidate genes were obtained from the GSE117993 dataset and the GSE93624 dataset by weighted gene co-expression network analysis (WGCNA) and differential analysis, followed by intersection with platelet-related genes. Based on this, diagnostic markers were screened by five machine learning algorithms. We constructed predictive models and molecular subtypes based on key markers. The models were evaluated using the GSE101794 dataset as the validation set, combined with receiver operating characteristic curves, decision curve analysis, clinical impact curves, and calibration curves. In addition, we performed pathway enrichment analysis and immune infiltration analysis for different molecular subtypes to assess their differences. Results: Through WGCNA and differential analysis, we successfully identified 44 candidate genes. Following this, employing five machine learning algorithms, we ultimately narrowed it down to five pivotal markers: GNA15, PIK3R3, PLEK, SERPINE1, and STAT1. Using these five key markers as a foundation, we developed a nomogram exhibiting exceptional performance. Furthermore, we distinguished two platelet-related subtypes of PCD through consensus clustering analysis. Subsequent analyses involving pathway enrichment and immune infiltration unveiled notable disparities in gene expression patterns, enrichment pathways, and immune infiltration landscapes between these subtypes. Conclusion: In this study, we have successfully identified five promising diagnostic markers and developed a robust nomogram with high predictive efficacy. Furthermore, the recognition of distinct PCD subtypes enhances our comprehension of potential pathogenic mechanisms and paves the way for future prospects in early diagnosis and personalized treatment. [ABSTRACT FROM AUTHOR]

Background: The natural history of Crohn's disease (CD) can result in complications requiring surgery. Pediatric data are scarce about major abdominal surgery. The IBD Registry from the Italian Society of Pediatric Gastroenterology, Hepatology, and Nutrition has been active since 2008 and collects data from major pediatric IBD centers in Italy. The aim of the present report was to explore the prevalence of major abdominal surgery among children affected by CD in an era when antitumor necrosis factor (anti-TNF-α) agents were already used so that we might appraise the incidence of surgical-related complications and identify the factors associated with postoperative disease recurrence., Methods: We retrospectively analyzed data from patients enrolled in the registry from January 2009 to December 2018. Patients with monogenic IBD and patients undergoing surgery for perianal disease were excluded., Results: In total, 135 of 1245 patients were identified. We report the prevalence of major abdominal surgery of 10.8%. Pediatric surgeons performed the procedure in 54.1% of cases, and a laparoscopic approach was used in 47.4% of surgical procedures. Seventeen patients (12.6%) experienced a total of 21 early postoperative complications, none of which was severe. A laparoscopic approach was the only factor negatively associated with the occurrence of postoperative complications (odds ratio, 0.22; 95% confidence interval, 0.06-0.8; P = .02). Fifty-four (40%) patients experienced postoperative endoscopic recurrence, and 33 (24.4%) of them experienced postoperative clinical recurrence. The postoperative treatment with anti-TNF-α drugs was significantly associated with a reduced risk of endoscopic recurrence (odds ratio, 0.19; 95% confidence interval, 0.05-0.79; P = .02)., Conclusion: In our cohort, the overall prevalence of major abdominal surgery was low, as well as the rate of surgical-related complications. Postoperative anti-TNF-α therapy seems be protective against endoscopic recurrence., (© The Author(s) 2024. 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.)

Exclusive enteral nutrition (EEN) is a first-line therapy for pediatric Crohn's disease (CD), but protective mechanisms remain unknown. We established a prospective pediatric cohort to characterize the function of fecal microbiota and metabolite changes of treatment-naive CD patients in response to EEN (German Clinical Trials DRKS00013306). Integrated multi-omics analysis identified network clusters from individually variable microbiome profiles, with Lachnospiraceae and medium-chain fatty acids as protective features. Bioorthogonal non-canonical amino acid tagging selectively identified bacterial species in response to medium-chain fatty acids. Metagenomic analysis identified high strain-level dynamics in response to EEN. Functional changes in diet-exposed fecal microbiota were further validated using gut chemostat cultures and microbiota transfer into germ-free Il10-deficient mice. Dietary model conditions induced individual patient-specific strain signatures to prevent or cause inflammatory bowel disease (IBD)-like inflammation in gnotobiotic mice. Hence, we provide evidence that EEN therapy operates through explicit functional changes of temporally and individually variable microbiome profiles., Competing Interests: Declaration of interests D. Haller served on the Microbiome Expert Panel from Reckitt Benckiser Health Limited. T.S. received lecture honoraria from Nutricia and MSD and travel support from Abbvie and Ferring outside the submitted work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Failure to thrive (FTT) refers to a condition where a child does not gain weight or grow at the expected rate for their age and gender. An accepted definition includes a weight less than the lowest acceptable range on standardized growth charts. FTT is often a diagnostic challenge for providers treating children with mixed etiologies. This report discusses the case of an 11-year-old female with a diagnosis of Crohn's disease and avoidant and restrictive food intake disorder (ARFID). Management by an interprofessional healthcare team has been difficult, given the multifactorial nature of the patient's weight loss. This report suggests that behavioral and psychological aspects, such as aversion to eating and reluctance to experiment with different foods, may align with symptoms of Crohn's disease in children. It also emphasizes the importance of timely diagnosis and appropriate interventions, as they can mitigate psychological and developmental setbacks., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Valencia et al.)

Gut dysbiosis is closely related to dysregulated microRNAs (miRNAs) in the intestinal epithelial cells, which plays an important role in the pathogenesis of Crohn's disease (CD). We investigated the relationship between fecal gut microbiome (GM) and intestinal tissue miRNAs in different stages of pediatric CD. Metagenomic analysis and miRNA sequencing were conducted to examine the GM and intestinal miRNA profiles of CD patients before and after clinical induction therapy and the controls. Twenty-seven newly diagnosed, therapy-naïve pediatric patients with active CD and 11 non-inflammatory bowel disease (IBD) controls were recruited in this study. Among CD patients, 11 patients completed induction treatment and reached clinical remission. Both GM and miRNA profiles were significantly changed between CD patients and controls. Seven key bacteria were identified at species level including Defluviitalea raffinosedens , Thermotalea metallivorans , Roseburia intestinalis , Dorea sp. AGR2135, Escherichia coli , Shigella sonnei , and Salmonella enterica , the exact proportions of which were further validated by real-time quantitative PCR analysis. Eight key miRNAs were also identified including hsa-miR-215-5p, hsa-miR-194-5p, hsa-miR-12135, hsa-miR-509-3-5p, hsa-miR-212-5p, hsa-miR-4448, hsa-miR-501-3p, and hsa-miR-503-5p. The functional enrichment analysis of differential miRNAs indicated the significantly altered cyclin protein, cyclin-dependent protein, and cell cycle pathway. The close interactions between seven key bacteria and eight key miRNAs were further investigated by miRNA target prediction. The association between specific miRNA expressions and key gut bacteria at different stages of CD supported their important roles as potential molecular biomarkers. Understanding the relationship between them will help us to explore the molecular mechanisms of CD., Importance: Since previous studies have focused on the change of the fecal gut microbiome and intestinal tissue miRNA in pediatric Crohn's disease (CD), the relationship between them in different stages is still not clear. This is the first study to explore the gut microbiota and miRNA and their correlations with the Pediatric Crohn's Disease Activity Index (PCDAI). Crohn's Disease Endoscopic Index of Severity (CDEIS), and calprotectin, by applying two omics approach in three different groups (active CD, CD in remission with exclusive enteral nutrition or infliximab induction therapy, and the healthy controls). Both gut microbiome structure and the miRNA profiles were significantly changed in the different stage of CD. Seven key gut microbiome at species and eight key miRNAs were found, and their close interactions were further fully investigated by miRNA target prediction., Competing Interests: The authors declare no conflict of interest.

Background Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), presents significant challenges, particularly in pediatric patients. Vitamin D deficiency has been associated with IBD, but its role in disease activity and remission remains unclear. This study investigates the relationship between serum vitamin D levels and IBD markers, including Pediatric Crohn's Disease Activity Index (PCDAI), Pediatric Ulcerative Colitis Activity Index (PUCAI), fecal calprotectin levels, and endoscopy findings. It also explores racial and ethnic disparities in these relationships. Methodology A retrospective study was conducted involving 51 pediatric patients with IBD from the Nemours Children's Health EMR system. Inclusion criteria required documented serum vitamin D levels at diagnosis and post-treatment, and at least one post-treatment assessment of PUCAI/PCDAI, calprotectin, or endoscopy. The study employed Spearman and Pearson correlation tests to analyze the associations between vitamin D levels and IBD markers. Ethnicity and race were analyzed using t-tests and chi-square tests. Results No statistically significant correlations were found between changes in serum vitamin D levels and IBD markers (endoscopy results, calprotectin levels, PUCAI/PCDAI scores) for both UC and CD. Analysis of racial and ethnic disparities revealed that Hispanic patients had significantly higher post-treatment calprotectin levels compared to non-Hispanics, although other markers showed no significant differences. Vitamin D levels did not significantly differ between racial or ethnic groups. Conclusions This study found no significant correlation between serum vitamin D levels and IBD activity markers in pediatric patients. Despite initial hypotheses, vitamin D levels do not appear to be useful in assessing IBD remission or disease state. Racial and ethnic disparities in IBD severity were observed, but further research with larger sample sizes and more consistent data collection is needed to draw more definitive conclusions., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Nemours Office of Human Subjects Protection issued approval 1910359. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Centner et al.)

Purpose: Identifying reliable prognostic factors for pediatric-onset Crohn's disease (CD) is important for guiding early treatment. This study aimed to evaluate the validity of various clinical parameters for predicting long-term intestinal complications in pediatric-onset CD patients with CD in Taiwan., Methods: This was a single-center, retrospective study. Patients diagnosed with CD under 18 years of age at our hospital between January 1999 and December 2021 were enrolled. The baseline clinical variables and the Pediatric Crohn's Disease Activity Index (PCDAI) were obtained. Patients were categorized into low-, medium-, or high-risk groups based on the 2020 European Crohn's and Colitis Organization and European Society for Pediatric Gastroenterology Hepatology and Nutrition (ECCO-ESPGHAN) guidelines. The primary endpoint was the occurrence of new intestinal complications., Results: Among 53 enrolled patients (33 males and 20 females), 8 patients (33.96%) developed intestinal complications during the follow-up period (median 6.42 years, 3.17-9.75 years). Patients in the initial ECCO-ESPGHAN medium- or high-risk group had a 4.71-fold higher risk of intestinal complications than those in the low-risk group [hazard ratio = 4.71, p = 0.023] after adjusting for PCDAI in the multivariate Cox proportional hazard analysis. The other clinical variables did not reach statistical significance in predicting intestinal complications. The positive and negative predictive values of the ECCO-ESPGHAN stratification method for intestinal complications were 48.15% and 80.77%, respectively., Conclusions: ECCO-ESPGHAN risk stratification is an effective early predictor of long-term intestinal complications in the Taiwanese population and may be used in clinical practice to guide early advanced therapy., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: The incidence of pediatric Crohn's disease (PCD) is increasing worldwide every year. The challenges in early diagnosis and treatment of PCD persist due to its inherent heterogeneity. This study's objective was to discover novel diagnostic markers and molecular subtypes aimed at enhancing the prognosis for patients suffering from PCD., Methods: Candidate genes were obtained from the GSE117993 dataset and the GSE93624 dataset by weighted gene co-expression network analysis (WGCNA) and differential analysis, followed by intersection with platelet-related genes. Based on this, diagnostic markers were screened by five machine learning algorithms. We constructed predictive models and molecular subtypes based on key markers. The models were evaluated using the GSE101794 dataset as the validation set, combined with receiver operating characteristic curves, decision curve analysis, clinical impact curves, and calibration curves. In addition, we performed pathway enrichment analysis and immune infiltration analysis for different molecular subtypes to assess their differences., Results: Through WGCNA and differential analysis, we successfully identified 44 candidate genes. Following this, employing five machine learning algorithms, we ultimately narrowed it down to five pivotal markers: GNA15, PIK3R3, PLEK, SERPINE1, and STAT1. Using these five key markers as a foundation, we developed a nomogram exhibiting exceptional performance. Furthermore, we distinguished two platelet-related subtypes of PCD through consensus clustering analysis. Subsequent analyses involving pathway enrichment and immune infiltration unveiled notable disparities in gene expression patterns, enrichment pathways, and immune infiltration landscapes between these subtypes., Conclusion: In this study, we have successfully identified five promising diagnostic markers and developed a robust nomogram with high predictive efficacy. Furthermore, the recognition of distinct PCD subtypes enhances our comprehension of potential pathogenic mechanisms and paves the way for future prospects in early diagnosis and personalized treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tang, Huang, Che, Yang, Pu, Liu and Li.)

Background: Pediatric inflammatory bowel disease (PIBD) affects different age groups and its incidence is increasing worldwide. However, there is a lack of research focusing on age subgroups in Asian countries. In this nationwide population-based study, we investigated the epidemiology of PIBD among different age subgroups in Korea., Methods: We analyzed Korean health administration data from 2005 to 2016. Data were divided by age at diagnosis as follows: group 1, 0-1 years; group 2, 2-5 years; group 3, 6-9 years; group 4, 10-16 years. We analyzed the overall incidence, temporal changes, and regional differences by age subgroups, using Poisson regression analysis., Results: From 2005 to 2016, 2734 inflammatory bowel disease (IBD) cases were diagnosed among patients under 17 years of age. In the overall population, the incidence rate of PIBD over the entire study period was 2.248/10 5  person-years (PY), significantly increasing from 1.173/10 5  PY in 2005-2007 to 3.267/10 5  PY in 2014-2016. The incidence rates in groups 1 and 2 remained unchanged, whereas those of groups 3 and 4 increased significantly. The same trend was observed when analyzed separately for Crohn's disease (CD) and ulcerative colitis (UC). The incidence rates of CD in groups 3 and 4 showed differences between metropolitan and non-metropolitan areas, whereas those in groups 1 and 2, and UC of all age subgroups showed no difference., Conclusions: The temporal trend and regional differences of PIBD differed among age subgroups, suggesting that genetic and environmental factors have varying impacts on IBD development across different subgroups., (© 2024 Japan Pediatric Society.)