Composition and function of the pediatric colonic mucosal microbiome in untreated patients with ulcerative colitis

Abstract

Inflammatory bowel diseases (IBD) are chronic intestinal inflammatory disorders characterized by a complex disruption of the physiologic interaction between the host immune system and intestinal microbes precipitated by environmental factors. Numerous observations indicate the altered composition and function of the intestinal microbiome of patients with ulcerative colitis (UC), a subtype of IBD. The accuracy of these results may be limited by confounding factors, such as concurrent medication use. To address these limitations, we examined the colonic mucosal microbiome of pediatric patients with UC prior to initiating treatment. Based on bacterial 16S rRNA gene sequencing, we identified a significant decrease in the phylum Verrucomicrobia in patients with UC. At the genus level, we observed a significant decrease in the short chain fatty acid producer Roseburia. Despite these compositional changes, we did not identify inferred gene content differences between the UC and control groups. To determine if microbial taxa may be associated with clinical outcomes, we retrospectively assessed the clinical course of the UC patients. Despite similar metrics of OTU richness and diversity, multiple OTU differences were observed between patients who responded to therapy and those who did not. Our observations regarding the mucosal microbiome and the associations with differential clinical outcomes support the contributions of gut microbes to disease onset and modulation.

Gut microbiota and IBD: causation or correlation?

“…Although there has been debate over the degree of dysbiosis in paediatric patients, particularly at the mucosal level, most studies have shown substantial differences between diseased and healthy individuals 34,35 . Thus, dysbiotic changes were described in stool and mucosal biopsies from newly diagnosed, treatment-naive children with Crohn's disease, suggesting that dysbiosis might precede clinical disease and develop independently of long-standing inflammation and/or medical therapy 36 .…”

Roles for Intestinal Bacteria, Viruses, and Fungi in Pathogenesis of Inflammatory Bowel Diseases and Therapeutic Approaches

“…Characteristic compositional changes observed in patients with IBD include decreased bacterial diversity, with expansion of putative aggressive groups (such as Proteobacteria, Fusobacterium species, and Ruminococcus gnavus ) combined with decreases in protective groups (such as Lachnospiraceae, Bifidobacterium species, Roseburia, and Sutterella) (Table 1) 4, 6, 10, 13, 69–73 . This dysbiosis is present at early stages of disease progression, before patients have been treated, but is affected by prior use of antibiotics 61, 69, 73 .…”

Roadmap for investigating epigenome deregulation and environmental origins of cancer

“…Infection agents and chronic inflammation are also known to affect epigenetic states. For example, the maternal microbiome and the postnatal gut microbiome seem to play a role in modulating intestinal mucosal epigenetic patterning and consequent susceptibility to inflammatory bowel disease (IBD) and young‐onset colorectal cancer . Another example is the epigenetic field cancerization observed in gastric cancer, where chronic inflammation induced by Helicobacter pylori is responsible for aberrant DNA methylation .…”