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Treatment-Specific Composition of the Gut Microbiota Is Associated With Disease Remission in a Pediatric Crohn's Disease Cohort.

ABSTRACT: BACKGROUND:The 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. METHODS:16S 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. 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 before and during antibiotic treatment with metronidazole accurately classified disease remission in this treatment group (area under the curve [AUC], 0.879; 95% confidence interval, 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, 0.8; P = 0.24). CONCLUSIONS:MET 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.

SUBMITTER: Sprockett D

PROVIDER: S-EPMC7185687 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Treatment-Specific Composition of the Gut Microbiota Is Associated With Disease Remission in a Pediatric Crohn's Disease Cohort.

Sprockett Daniel D Fischer Natalie N Boneh Rotem Sigall RS Turner Dan D Kierkus Jarek J Sladek Malgorzata M Escher Johanna C JC Wine Eytan E Yerushalmi Baruch B Dias Jorge Amil JA Shaoul Ron R Kori Michal M Snapper Scott B SB Holmes Susan S Bousvaros Athos A Levine Arie A Relman David A DA

Inflammatory bowel diseases 20191101 12

<h4>Background</h4>The 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.<h4>Methods</h4>16S rRNA-based microbiota profiling was performed on stool samples from 67 patients in a multinational, randomized, con ...[more]

PMID: 31276165

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Project description:BackgroundThe dysbiosis of the gut microbiome is evident in Crohn's disease (CD) compared with healthy controls (HC), although the alterations from active CD to remission after treatment are unclear.AimTo characterize the mucosa-associated gut microbiota in patients with CD before and after the induction therapy.MethodsThe basic information was collected from the subjects and the CD activity index (CDAI) was calculated in patients. A 16S rRNA sequencing approach was applied to determine the structures of microbial communities in mucosal samples including the terminal ileal, ascending colon, descending colon and rectum. The composition and function of mucosa-associated gut microbiota were compared between samples from the same cohort of patients before and after treatment. Differential taxa were identified to calculate the microbial dysbiosis index (MDI) and the correlation between MDI and CDAI was analyzed using Pearson correlation test. Predictive functional profiling of microbial communities was obtained with PICRUSt.ResultsThere were no significant differences in microbial richness among the four anatomical sites in individuals. Compared to active disease, the alpha diversity of CD in remission was increased towards the level of HC compared to the active stage. The principal coordinate analysis revealed that samples of active CD were clearly separated from those in remission, which clustered close to HC. Sixty-five genera were identified as differentially abundant between active and quiescent CD, with a loss of Fusobacterium and a gain of potential beneficial bacteria including Lactobacillus, Akkermansia, Roseburia, Ruminococcus and Lachnospira after the induction of remission. The combination of these taxa into a MDI showed a positive correlation with clinical disease severity and a negative correlation with species richness. The increased capacity for the inferred pathways including Lipopolysaccharide biosynthesis and Lipopolysaccharide biosynthesis proteins in patients before treatment negatively correlated with the abundance of Roseburia, Ruminococcus and Lachnospira.ConclusionThe dysbiosis of mucosa-associated microbiota was associated with the disease phenotype and may become a potential diagnostic tool for the recurrence of disease.

Dataset Information

Treatment-Specific Composition of the Gut Microbiota Is Associated With Disease Remission in a Pediatric Crohn's Disease Cohort.

Publications

Treatment-Specific Composition of the Gut Microbiota Is Associated With Disease Remission in a Pediatric Crohn's Disease Cohort.

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