RT Journal Article
SR Electronic
T1 Treatment-Specific Composition of Gut Microbiota Is Associated with Disease Remission in a Pediatric Crohn’s Disease Cohort
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 412890
DO 10.1101/412890
A1 Daniel Sprockett
A1 Natalie Fischer
A1 Rotem Sigall Boneh
A1 Dan Turner
A1 Jarek Kierkus
A1 Malgorzata Sladek
A1 Johanna C. Escher
A1 Eytan Wine
A1 Baruch Yerushalmi
A1 Jorge Amil Dias
A1 Ron Shaoul
A1 Michal Kori
A1 Scott B. Snapper
A1 Susan Holmes
A1 Athos Bousvaros
A1 Arie Levine
A1 David A. Relman
YR 2018
UL http://biorxiv.org/content/early/2018/09/10/412890.abstract
AB Objectives The beneficial effects of antibiotics 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.Methods 16S rRNA-based microbiota profiling was performed on stool samples from 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 classification models to classify remission or predict treatment response.Results Both 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 pre-antibiotic microbiota profiles predicted disease remission at week 4 with modest accuracy (AUC of 0.8, P = 0.24).Conclusions MET and MET+AZ antibiotic regimens 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.What is knownThe composition of the intestinal microbiota of pediatric Crohn’s disease patients is altered, and has low diversityAntibiotics disturb the intestinal microbiota in an individualized fashion that may help explain different clinical responsesThe combination of metronidazole and azithromycin (MET+AZ) is more effective than metronidazole alone (MET) for inducing disease remission in some CD patientsWhat is newMET and MET+AZ cause distinct changes in the gut microbiota of pediatric CD patientsEach regimen induces a specific remission-associated microbiota community configurationmDisease remission after either antibiotic regimen is characterized by a higher abundance of Lactobacillus