title: Gut microbiota differs between children with Inflammatory Bowel Disease and healthy siblings in taxonomic and functional composition: a metagenomic analysis.
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-WhitneyU-test false discovery rate (MWU FDR) = 0.011]. In UC, bacteria positively influencing gut homeostasis, e.g.,Eubacterium rectaleandFaecalibacterium prausnitzii, were significantly reduced in abundance (MWU FDR = 0.05). Known pathobionts likeEscherichia coliwere enriched in UC patients (MWU FDR = 0.084). Moreover,E. coliabundance 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 & NOTEWORTHYIn 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.
authors.affiliation: Children's Hospital, University Medical Center, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Knoll
authors.affiliation: European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Forslund
authors.affiliation: European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.
authors.forename: Jens Roat
authors.initials: JR
authors.lastname: Kultima
authors.affiliation: Children's Hospital, University Medical Center, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Claudius U
authors.initials: CU
authors.lastname: Meyer
authors.affiliation: Children's Hospital, University Medical Center, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kullmer
authors.affiliation: European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.|Institute of Microbiology, ETH Zurich, Zurich, Switzerland.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sunagawa
authors.affiliation: European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.|Molecular Medicine Partnership Unit, University of Heidelberg and European Molecular Biology Laboratory, Heidelberg, Germany.|Max Delbrück Centre for Molecular Medicine, Berlin, Germany; and.|Department of Bioinformatics, Biocenter, Würzburg, Germany.
authors.forename: Peer
authors.initials: P
authors.lastname: Bork
authors.affiliation: Children's Hospital, University Medical Center, Johannes Gutenberg University, Mainz, Germany; stephan.gehring@uni-mainz.de.
authors.forename: Stephan
authors.initials: S
authors.lastname: Gehring
mesh_terms: D000293:Adolescent; D002648:Child; D005243:Feces / Q000382:microbiology*; D005260:Female; D000069196:Gastrointestinal Microbiome; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000382:microbiology*; D007413:Intestinal Mucosa / Q000382:microbiology*; D008297:Male; D054892:Metagenome; D035781:Siblings; D055815:Young Adult
keywords: fecal microbiota transplantation; inflammatory bowel diseases; metagenomics; microbiome; pediatric gastroenterology