BACKGROUND AND AIMS: The pathophysiology of pediatric inflammatory bowel disease (PIBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is not entirely understood. Dysregulation of the intestinal microbiome is recognized as both a disease-driving and a potential therapeutic target. This study aimed to systematically analyze gut microbiome compositions and its applicability as a biomarker for disease progress and treatment response. METHODS: Bibliographic and nucleotide databases were searched. Raw 16S-rRNA sequencing reads were subjected to a uniform downstream dada2/phyloseq pipeline to extract taxonomy, community structure, and abundance information. Patient metadata were extracted from publications, and study authors were contacted for further details if required. RESULTS: Twenty-six studies comprising 3956 stool samples (CD 41%, UC 36%, 23% healthy) were included in the analyses. Median age of individuals was 12 (interquartile range 4). Sex distribution was comparable. Alpha diversity was reduced between the healthy and both UC and CD treatment-naïve groups (P < .001) and further reduced with increasing clinical disease activity. Beta diversity revealed altered community structure in treatment-naïve children with PIBD (P < .001). This alteration remained in patients in clinical remission (P < .001). Machine learning models discriminated between treatment-naïve patients with CD or UC with an area under the receiver operating characteristics curve (AUROC) of 98%. Microbial communities differed between patient responders versus nonresponders to treatment (P < .001). Further, microbial community profiling distinguished treatment response (eg, steroid, nutrition, or TNFα) with AUROCs of 82%-90%. CONCLUSIONS: Gut microbial community structure is substantially altered in active and inactive PIBD and may be utilized as a biomarker for differentiating PIBD subtype and predicting treatment response.

We identified 26 studies on the gut microbiome in pediatric patients with IBD compiling a total of 3956 stool samples (CD 41%, UC 36%, 23% healthy) revealing microbial community structures unique to patients with CD and UC. These community patterns allow for the distinction of PIBD type and prediction of treatment response.

Department of Clinical and Toxicological Analysis School of Pharmaceutical Sciences Universidade de Sao Paulo São Paulo Brazil

Department of Medical Microbiology 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czechia

Department of Medicine Farncombe Family Digestive Health Research Institute McMaster University Hamilton ON Canada

Department of Paediatrics 1 Medical University of Innsbruck Innsbruck Austria

Department of Paediatrics 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czechia

Department of Pediatric Gastroenterology and Nutrition Amsterdam UMC Location AMC and VUmc Amsterdam The Netherlands

Department of Pediatrics Dr von Hauner Children's Hospital University Hospital LMU Munich Munich Germany

Department of Pediatrics University of Toronto Toronto ON Canada

Division of Gastroenterology and Hepatology Rutgers Robert Wood Johnson Medical School New York NY USA

Division of Gastroenterology Hepatology and Nutrition Children's Hospital of Philadelphia Perelman School of Medicine at the University of Pennsylvania Philadelphia PA USA

Division of Gastroenterology Hepatology and Nutrition Department of Pediatrics and IBD Centre SickKids Hospital University of Toronto Toronto ON Canada

Division of Gastroenterology Hepatology and Nutrition Department of Pediatrics McMaster University Hamilton ON Canada

Division of Pediatric Gastroenterology Department of Pediatrics University of Alberta Edmonton AB Canada

Gastroenterology Digestive Endoscopy and Nutrition Unit Bambino Gesù Children's Hospital IRCCS Rome Italy

Immunology Rheumatology and Infectious Diseases Research Area Unit of Microbiome Bambino Gesù Children's Hospital IRCCS Rome Italy

Institute of Cell Biology Biocenter Medical University of Innsbruck Innsbruck Austria

Shaare Zedek Medical Center The Hebrew University of Jerusalem Jerusalem Israel

Vatche and Tamar Manoukian Division of Digestive Diseases David Geffen School of Medicin University of California Los Angeles Los Angeles CA USA

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Inflamm Bowel Dis. 2025 Oct 1;31(10):2953. doi: 10.1093/ibd/izaf200. PubMed

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