Published online Jun 14, 2020. doi: 10.3748/wjg.v26.i22.3098
Peer-review started: January 6, 2020
First decision: January 19, 2020
Revised: March 30, 2020
Accepted: May 28, 2020
Article in press: May 28, 2020
Published online: June 14, 2020
Several studies have employed animal models to explore the association between microbiota and interleukin (IL)10 signaling; however, limited information is available about the human microbiome. To the best of our knowledge, this is the first report of microbial dysbiosis in this sub-population of inflammatory bowel diseases (IBD) patients with IL10RA mutations.
Patients with IL10RA mutations had early disease onset and experienced more severe colitis. Recent studies have revealed an association between host genetic variants and gut microbial changes; in addition, the underlying interactions were found to contribute to the onset and severity of IBD. However, the role of microbiota in patients with infantile-onset IBD who have IL10 signaling defects is not clear. Our findings may facilitate further attempts to develop microbial therapeutics in these patients.
We aimed to characterize the microbiome in patients with IL10RA mutations and to explore the association between gut dysbiosis and disease severity. We observed a reduced diversity and increased variability of gut microbiome in patients with IL10RA mutations. We also explored the association between intestinal dysbiosis and the disease severity in these patients. Further studies should focus on the precise role of the microbiota in the etiology of IBD in terms of host genetic susceptibility; this constitutes an attractive target for a given host genome.
Fecal samples were collected from patients who were diagnosed with loss-of-function mutations in the IL10RA gene. Age-matched volunteer children were recruited as healthy controls. Patients with Crohn's disease (CD) were used as disease controls to standardize the antibiotic exposure. Microbial DNA was extracted from the fecal samples. All analyses were based on the 16S rRNA gene sequencing data.
Seventeen patients with IL10RA mutations, 17 patients with pediatric CD, and 26 healthy children were included. Both patients with IL10RA mutations and those with CD exhibited a reduced diversity of gut microbiome with increased variability. The relative abundance of Firmicutes was substantially increased in the IL10RA group. On further comparison of the relative abundance of taxa between patients with IL10RA mutations and healthy children, 13 taxa showed significant differences. The IL10RA-specific dysbiosis indices exhibited a significant positive correlation with weighted pediatric CD activity index and simple endoscopic score for CD. This observational study was a pilot effort to characterize IL10RA-specific microbial alterations and does not permit any causal inferences.
In patients with IL10RA mutations and early onset IBD, gut dysbiosis showed a moderate association with disease severity. In this study, clinical variables of IL10RA-deficient patients (such as disease course) were linked with changes in the stool microbiome, which implies potential clinical relevance of the changes in microbial populations.
16S rRNA sequencing has its limitations; shotgun metagenomic sequencing with a higher taxonomic resolution may capture microbial shifts in full complexity. Further investigations may be warranted to identify the shifts in functional or metabolic capabilities of the microbiome. Prospective trials enrolling larger treatment-naive populations at high risk with longitudinal follow-up would provide insights into the role of microbes in the onset of inflammation.