Microbiota-Host Symbiosis In First-Onset Pediatric Inflammatory Bowel Disease

Abstract

In recent years, the association between inflammatory bowel diseases (IBDs) and gut microbiota has been extensively studied in adults using post-treatment cohorts of patients. However, microbial composition and functional interplay between host genetics and microorganisms in newly diagnosed early IBD onset remain poorly defined. Using colonoscopic mucosal washes to collect mucosal-luminal microbiota from different intestinal locations, we studied the gut microbiome in a large number of children with either Crohn’s disease (CD) or ulcerative colitis (UC). Although no significant difference in the diversity was evident between the gut microbiota of IBD-affected and control children, the microbiome of IBD subjects is characterized by an increased abundance of potent hydrogen sulfide (H2S) producers and decreased abundance of beneficial butyrate producers. Microbiota and proteomic profiling revealed that the abundance of Atopobium parvulum, a potent H2S producer, was associated with increased CD severity and a concurrent reduction in the expression of the host H2S detoxification pathway. Gnotobiotic and conventionalized colitis-susceptible interleukin-10-deficient (Il-10-/-) mice showed that A. parvulum induces severe colitis, a phenotype requiring the presence of the gut microbiota. In addition, administration of bismuth, an H2S scavenger, prevented A. parvulum-induced colitis in Il-10-/- mice. Our findings have identified A. parvulum as a major mediator of inflammation severity. We also reveal an imbalance between the H2S production and detoxification in the gastrointestinal tract of pediatric IBD patients. Altogether, our findings provide new avenues for diagnostics as well as therapies to treat IBD.