Alterations in the gut microbiome of children with severe ulcerative colitis

Abstract

Background Although the role of microbes in disease pathogenesis is well established, data describing the variability of the vast microbiome in children diagnosed with ulcerative colitis (UC) are lacking. This study characterizes the gut microbiome in hospitalized children with severe UC and determines the relationship between microbiota and response to steroid therapy. Methods Fecal samples were collected from 26 healthy controls and 27 children hospitalized with severe UC as part of a prospective multi-center study. DNA extraction, PCR amplification of bacterial 16S rRNA, and microarray hybridization were performed. Results were analyzed in Genespring GX 11.0 comparing healthy controls to children with UC, and steroid responsive (n=17) to non-responsive patients (n=10). Results Bacterial signal strength and distribution showed differences between UC and healthy controls (adjusted p<0.05) for Phylum, Class, Order, Family, Genus, and Phylospecies levels with reduction in Clostridia and an increase in Gamma-proteobacteria. The number of microbial phylospecies was reduced in UC (266±69) vs. controls (758±3, p<0.001), as was the Shannon diversity index (6.1±0.23 vs. 6.49±0.04, respectively; p<0.0001). Steroids non-responders harbored less phylospecies than responders (142±49 vs. 338±62, p=0.013). Conclusions Richness, evenness, and biodiversity of the gut microbiome were remarkably reduced in children with UC, compared to healthy controls. Children who did not respond to steroids harbored a microbiome that was even less rich than steroid responders. This study is the first to characterize the gut microbiome in a large cohort of pediatric patients with severe ulcerative colitis and describes changes in the gut microbiome as a potential prognostic feature.

Microbiota of De-Novo Pediatric IBD: Increased Faecalibacterium Prausnitzii and Reduced Bacterial Diversity in Crohn's But Not in Ulcerative Colitis

“…prausnitzii is likely to have an important role in CD; however, its role may be more complex than our current understanding. It is clear from the seminal study of Sokol et al ( 34 ) that this single species is positively associated with an improved UC ( 33 ). Th e study of Michail et al ( 33 ) demonstrated alterations in the fecal microbiota of pediatric UC vs. healthy controls, but also showed that UC non-responders to steroid treatment demonstrated fewer phylotypes within their fecal samples compared with responders when examined by microarray.…”

The Cystic Fibrosis Airway Microbiome

“…Evidence from several gastrointestinal microbiota studies (Michail et al 2011;Walker et al 2011) has shown that, as in the CF airways, loss of microbiota diversity is a hallmark of chronic inflammatory disease. This suggests that immune homeostasis and colonization resistance (the ability to withstand invasion by pathogenic species) is predicated on appropriate mucosal colonization and that perturbations to the microbiota, particularly those that lead to loss of community diversity and increased abundance of specific immunogenic species, may drive these persistent inflammatory responses.…”

0991 Relationship between the microbiota in different sections of the gastrointestinal tract, and the body weight of broiler chickens

“…In our study, similar results were observed in the cecum, although the reverse was seen in the crop and ileum. Several studies suggested that reduced gut microbial diversity is correlated with several diseases such as inflammatory bowel disease and obesity-associated diabetes (Chang et al 2008;Michail et al 2012;Murri et al 2013;Turnbaugh et al 2009). While several other studies concluded that microbial diversity is not related with these diseases (Mejia-Leon et al 2014;de Goffau et al 2014;Walters et al 2014), these results are controversial as of now, and thus, more studies are needed.…”