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bioRxiv · 10.1101/412890

Treatment-Specific Composition of Gut Microbiota Is Associated with Disease Remission in a Pediatric Crohn’s Disease Cohort

Sprockett, D.·Fischer, N.·Boneh, R. S.·Turner, D.·Kierkus, J.·Sladek, M.·Escher, J.·Wine, E.·Yerushalmi, B.·Dias, J. A.·Shaoul, R.·Kori, M.·Snapper, S.·Holmes, S.·Bousvaros, A.·Levine, A.·Relman, D. A.
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Abstract

BackgroundThe beneficial effects of antibiotics in Crohns 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.\n\nMethods16S 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.\n\nResultsBoth 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).\n\nConclusionsMET 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.\n\nSummaryWe investigated the impact of metronidazole and metronidazole plus azithromycin on the gut microbiota in pediatric Crohns disease. Disease remission was associated with a treatment-specific microbiota configuration, and could be predicted based on pre-antibiotic microbiota profiles.

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Sprockett, D., Fischer, N., Boneh, R. S., Turner, D., Kierkus, J., Sladek, M., Escher, J., Wine, E., Yerushalmi, B., Dias, J. A., Shaoul, R., Kori, M., Snapper, S., Holmes, S., Bousvaros, A., Levine, A., Relman, D. A.. 2018-09-10. Treatment-Specific Composition of Gut Microbiota Is Associated with Disease Remission in a Pediatric Crohn’s Disease Cohort. https://doi.org/10.1101/412890

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