Helmholtz Gemeinschaft


Gut microbiota differs between children with inflammatory bowel disease and healthy siblings in taxonomic and functional composition: a metagenomic analysis

PDF (Accepted manuscript (final draft)) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
[img] Other (Supplemental information)

Item Type:Article
Title:Gut microbiota differs between children with inflammatory bowel disease and healthy siblings in taxonomic and functional composition: a metagenomic analysis
Creators Name:Knoll, R.L. and Forslund, K. and Kultima, J.R. and Meyer, C.U. and Kullmer, U. and Sunagawa, S. and Bork, P. and Gehring, S.
Abstract:Current treatment for pediatric inflammatory bowel disease (IBD) patients is often ineffective, with serious side effects. Manipulating the gut microbiota via fecal microbiota transplantation (FMT) is an emerging treatment approach but remains controversial. We aimed to assess the composition of the fecal microbiome through a comparison of pediatric IBD patients to their healthy siblings, evaluating risks and prospects for FMT in this setting. A case-control (sibling) study was conducted analyzing fecal samples of six children with Crohn's disease (CD), six children with ulcerative colitis (UC) and 12 healthy siblings by metagenomic sequencing. In addition, lifetime antibiotic intake was retrospectively determined. Species richness and diversity were significantly reduced in UC patients compared with control [Mann-Whitney U-test false discovery rate (MWU FDR) = 0.011]. In UC, bacteria positively influencing gut homeostasis, e.g., Eubacterium rectale and Faecalibacterium prausnitzii, were significantly reduced in abundance (MWU FDR = 0.05). Known pathobionts like Escherichia coli were enriched in UC patients (MWU FDR = 0.084). Moreover, E. coli abundance correlated positively with that of several virulence genes (SCC > 0.65, FDR < 0.1). A shift toward antibiotic-resistant taxa in both IBD groups distinguished them from controls [MWU Benjamini-Hochberg-Yekutieli procedure (BY) FDR = 0.062 in UC, MWU BY FDR = 0.019 in CD). The collected results confirm a microbial dysbiosis in pediatric UC, and to a lesser extent in CD patients, replicating associations found previously using different methods. Taken together, these observations suggest microbiotal remodeling therapy from family donors, at least for children with UC, as a viable option.NEW & NOTEWORTHY In this sibling study, prior reports of microbial dysbiosis in IBD patients from 16S rRNA sequencing was verified using deep shotgun sequencing and augmented with insights into the abundance of bacterial virulence genes and bacterial antibiotic resistance determinants, seen against the background of data on the specific antibiotic intake of each of the study participants. The observed dysbiosis, which distinguishes patients from siblings, highlights such siblings as potential donors for microbiotal remodeling therapy in IBD.
Keywords:Metagenomics, Microbiome, Pediatric Gastroenterology, Inflammatory Bowel Disease, Fecal Microbiota Transplantation
Source:American Journal of Physiology Gastrointestinal and Liver Physiology
Publisher:American Physiological Society
Page Range:G327-G339
Date:1 April 2017
Additional Information:Copyright © 2016 the American Physiological Society
Official Publication:https://doi.org/10.1152/ajpgi.00293.2016
PubMed:View item in PubMed

Repository Staff Only: item control page


Downloads per month over past year

Open Access
MDC Library