Treatment-Specific Composition of Gut Microbiota Is Associated with Disease Remission in a Pediatric Crohn’s Disease Cohort
Treatment-Specific Composition of Gut Microbiota Is Associated with Disease Remission in a Pediatric Crohn’s Disease Cohort
Abstract BackgroundThe beneficial effects of antibiotics in Crohn’s disease (CD) depend in part on the gut microbiota but are inadequately understood. We investigated the impact of metronidazole (MET) and metronidazole plus azithromycin (MET+AZ) on the microbiota in pediatric CD, and the use of microbiota features as classifiers or predictors of disease remission. Methods16S rRNA-based microbiota profiling was performed on stool samples from 67 patients in a multinational, randomized, controlled, longitudinal, 12-week trial of MET vs. MET+AZ in children with mild to moderate CD. Profiles were analyzed together with disease activity, and then used to construct Random Forest models to classify remission or predict treatment response. ResultsBoth MET and MET+AZ significantly decreased diversity of the microbiota and caused large treatment-specific shifts in microbiota structure at week 4. Disease remission was associated with a treatment-specific microbiota configuration. Random Forest models constructed from microbiota profiles pre- and during antibiotic treatment with metronidazole accurately classified disease remission in this treatment group (AUC of 0.879, 95% CI 0.683, 0.9877; sensitivity 0.7778; specificity 1.000, P < 0.001). A Random Forest model trained on preantibiotic microbiota profiles predicted disease remission at week 4 with modest accuracy (AUC of 0.8, P = 0.24). ConclusionsMET and MET+AZ antibiotic regimens in pediatric CD lead to distinct gut microbiota structures at remission. It may be possible to classify and predict remission based in part on microbiota profiles, but larger cohorts will be needed to realize this goal. SummaryWe investigated the impact of metronidazole and metronidazole plus azithromycin on the gut microbiota in pediatric Crohn’s disease. Disease remission was associated with a treatment-specific microbiota configuration, and could be predicted based on pre-antibiotic microbiota profiles.
Turner Dan、Snapper Scott B.、Kierkus Jarek、Sladek Malgorzata、Escher Johanna C.、Wine Eytan、Holmes Susan、Levine Arie、Relman David A.、Kori Michal、Yerushalmi Baruch、Boneh Rotem Sigall、Shaoul Ron、Bousvaros Athos、Sprockett Daniel、Fischer Natalie、Dias Jorge Amil
The Juliet Keidan Institute of Pediatric Gastroenterology & Nutrition, Shaare Zedek Medical Center, The Hebrew University of JerusalemDivision of Gastroenterology, Hepatology, and Nutrition, Boston Children?ˉs Hospital||Division of Gastroenterology, Brigham and Women?ˉs Hospital, and Harvard Medical SchoolDepartment of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, The Children?ˉs Memorial Health InstituteDepartment of Pediatrics, Gastroenterology and Nutrition, Jagiellonian University Medical CollegeDepartment of Pediatric Gastroenterology, Erasmus MC-Sophia Children?ˉs HospitalDivision of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, University of AlbertaDepartment of Statistics, Stanford UniversityPediatric Gastroenterology and Nutrition Unit, Wolfson Medical Center||Sackler School of Medicine, Tel Aviv UniversityDepartment of Microbiology & Immunology, Stanford University School of Medicine||Division of Infectious Diseases & Geographic Medicine, Department of Medicine, Stanford University School of Medicine||Infectious Diseases Section, Veterans Affairs Palo Alto Health Care SystemPediatric Day Care Unit, Kaplan Medical CenterPediatric Gastroenterology Unit, Soroka University Medical Center, and Faculty of Health Sciences, Ben-Gurion University of the NegevPediatric Gastroenterology and Nutrition Unit, Wolfson Medical CenterPediatric Gastroenterology Unit, Ruth Children?ˉs Hospital, Rambam Medical CenterDivision of Gastroenterology, Hepatology, and Nutrition, Boston Children?ˉs HospitalDepartment of Microbiology & Immunology, Stanford University School of MedicineDivision of Infectious Diseases & Geographic Medicine, Department of Medicine, Stanford University School of MedicineDepartment of Pediatrics
医药卫生理论医学研究方法微生物学
pediatric Crohn’s diseasemicrobiotaantibioticsdisease remissionRandom Forest model
Turner Dan,Snapper Scott B.,Kierkus Jarek,Sladek Malgorzata,Escher Johanna C.,Wine Eytan,Holmes Susan,Levine Arie,Relman David A.,Kori Michal,Yerushalmi Baruch,Boneh Rotem Sigall,Shaoul Ron,Bousvaros Athos,Sprockett Daniel,Fischer Natalie,Dias Jorge Amil.Treatment-Specific Composition of Gut Microbiota Is Associated with Disease Remission in a Pediatric Crohn’s Disease Cohort[EB/OL].(2025-03-28)[2025-05-13].https://www.biorxiv.org/content/10.1101/412890.点此复制
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