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-Whitney -test false discovery rate (MWU FDR) = 0.011]. In UC, bacteria positively influencing gut homeostasis, e.g., and , were significantly reduced in abundance (MWU FDR = 0.05). Known pathobionts like were enriched in UC patients (MWU FDR = 0.084). Moreover, 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. 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.

Smarcad1 mediates microbiota-induced inflammation in mouse and coordinates gene expression in the intestinal epithelium

“…This may relate to the much lower expression of Smarcad1 in somatic type cells compared to embryonic stem cells, as shown by the Sachs et al study. Furthermore, the predominant localization of Smarcad1 in the stem and proliferative compartment of the intestinal epithelium is consistent with a global rather Disease associations shown represent one or more previous studies in feces/colon biopsies from humans or mouse [49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64]. Where the cited studies have shown contradicting interactions, the predominant interactions are indicated than locus-specific role, e.g., maintenance of heterochromatin through replication [10].…”

“…Another increased species is Ruminococcus gnavus, a member of the class Clostridia. Increased levels of R. gnavus have been linked to intestinal inflammatory diseases [50][51][52][53]80]. R. gnavus is a mucolytic bacterium which alters mucus protective function [54,81].…”

Variability of core microbiota in newly diagnosed treatment-naïve paediatric Inflammatory Bowel Disease patients

“…Our observation that Eubacterium spp. were less abundant in the IBD group compared to the healthy controls is in concordance with findings from previous studies (42,43,44).…”

Comparison of the microbial community structure between inflamed and non‐inflamed sites in patients with ulcerative colitis

“…Among those species, Eubacterium is categorized in cluster XIVa of the Clostridia , which have recently gained many attentions because of their anti‐inflammatory properties mediated by induction of regulatory T cells . Recently, the lower abundance of Eubacterium has also been shown in UC patients . A lower abundance of Butyricimonas with a negative correlation with pro‐inflammatory cytokines has recently been reported in patients with multiple sclerosis .…”

“…27 Recently, the lower abundance of Eubacterium has also been shown in UC patients. 28,29 A lower abundance of Butyricimonas with a negative correlation with pro-inflammatory cytokines has recently been reported in patients with multiple sclerosis. 30 In addition, Prevotella, which showed the greatest difference at both the inflamed and non-inflamed sites of UC from non-IBD controls in the present study, was reported to be less abundant in untreated multiple sclerosis patients, while this difference was ameliorated after the treatment.…”