Dataset Information

Compositional and Temporal Changes in the Gut Microbiome of Pediatric Ulcerative Colitis Patients Are Linked to Disease Course.

ABSTRACT: Evaluating progression risk and determining optimal therapy for ulcerative colitis (UC) is challenging as many patients exhibit incomplete responses to treatment. As part of the PROTECT (Predicting Response to Standardized Colitis Therapy) Study, we evaluated the role of the gut microbiome in disease course for 405 pediatric, new-onset, treatment-naive UC patients. Patients were monitored for 1 year upon treatment initiation, and microbial taxonomic composition was analyzed from fecal samples and rectal biopsies. Depletion of core gut microbes and expansion of bacteria typical of the oral cavity were associated with baseline disease severity. Remission and refractory disease were linked to species-specific temporal changes that may be implicative of therapy efficacy, and a pronounced increase in microbiome variability was observed prior to colectomy. Finally, microbial associations with disease-associated serological markers suggest host-microbial interactions in UC. These insights will help improve existing treatments and develop therapeutic approaches guiding optimal medical care.

SUBMITTER: Schirmer M

PROVIDER: S-EPMC6277984 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Publications

Compositional and Temporal Changes in the Gut Microbiome of Pediatric Ulcerative Colitis Patients Are Linked to Disease Course.

Schirmer Melanie M Denson Lee L Vlamakis Hera H Franzosa Eric A EA Thomas Sonia S Gotman Nathan M NM Rufo Paul P Baker Susan S SS Sauer Cary C Markowitz James J Pfefferkorn Marian M Oliva-Hemker Maria M Rosh Joel J Otley Anthony A Boyle Brendan B Mack David D Baldassano Robert R Keljo David D LeLeiko Neal N Heyman Melvin M Griffiths Anne A Patel Ashish S AS Noe Joshua J Kugathasan Subra S Walters Thomas T Huttenhower Curtis C Hyams Jeffrey J Xavier Ramnik J RJ

Cell host & microbe 20181001 4

Evaluating progression risk and determining optimal therapy for ulcerative colitis (UC) is challenging as many patients exhibit incomplete responses to treatment. As part of the PROTECT (Predicting Response to Standardized Colitis Therapy) Study, we evaluated the role of the gut microbiome in disease course for 405 pediatric, new-onset, treatment-naive UC patients. Patients were monitored for 1 year upon treatment initiation, and microbial taxonomic composition was analyzed from fecal samples an ...[more]

PMID: 30308161

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Project description:Dysbiosis of human gut microbiota has been reported in association with ulcerative colitis (UC) in both children and adults using either 16S rRNA gene or shotgun sequencing data. However, these studies used either 16S rRNA or metagenomic shotgun sequencing but not both. We sequenced feces samples from 19 pediatric UC and 23 healthy children ages between 7 to 21 years using both 16S rRNA and metagenomic shotgun sequencing. The samples were analyzed using three different types of data: 16S rRNA genus level abundance, microbial species and pathway abundance profiles. We demonstrated that (a) the alpha diversity of pediatric UC cases is lower than that of healthy controls; (b) the beta diversity within children with UC is more variable than within the healthy children; (c) several microbial families including Akkermansiaceae, Clostridiaceae, Eggerthellaceae, Lachnospiraceae, and Oscillospiraceae, contain species that are depleted in pediatric UC compared to controls; (d) a few associated species unique to pediatric UC, but not adult UC, were also identified, e.g. some species in the Christensenellaceae family were found to be depleted and some species in the Enterobacteriaceae family were found to be enriched in pediatric UC; and (e) both 16S rRNA and shotgun sequencing data can predict pediatric UC status with area under the receiver operating characteristic curve (AUROC) of close to 0.90 based on cross validation. We showed that 16S rRNA data yielded similar results as shotgun data in terms of alpha diversity, beta diversity, and prediction accuracy. Our study demonstrated that pediatric UC subjects harbor a dysbiotic and less diverse gut microbial population with distinct differences from healthy children. We also showed that 16S rRNA data yielded accurate disease prediction results in comparison to shotgun data, which can be more expensive and laborious. These conclusions were confirmed in an independent data set of 7 pediatric UC cases and 8 controls.

Dataset Information

Compositional and Temporal Changes in the Gut Microbiome of Pediatric Ulcerative Colitis Patients Are Linked to Disease Course.

Publications

Compositional and Temporal Changes in the Gut Microbiome of Pediatric Ulcerative Colitis Patients Are Linked to Disease Course.

Similar Datasets

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