A Modular Organization of the Human Intestinal Mucosal Microbiota and Its Association with Inflammatory Bowel Disease

Abstract

Abnormalities of the intestinal microbiota are implicated in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC), two spectra of inflammatory bowel disease (IBD). However, the high complexity and low inter-individual overlap of intestinal microbial composition are formidable barriers to identifying microbial taxa representing this dysbiosis. These difficulties might be overcome by an ecologic analytic strategy to identify modules of interacting bacteria (rather than individual bacteria) as quantitative reproducible features of microbial composition in normal and IBD mucosa. We sequenced 16S ribosomal RNA genes from 179 endoscopic lavage samples from different intestinal regions in 64 subjects (32 controls, 16 CD and 16 UC patients in clinical remission). CD and UC patients showed a reduction in phylogenetic diversity and shifts in microbial composition, comparable to previous studies using conventional mucosal biopsies. Analysis of weighted co-occurrence network revealed 5 microbial modules. These modules were unprecedented, as they were detectable in all individuals, and their composition and abundance was recapitulated in an independent, biopsy-based mucosal dataset 2 modules were associated with healthy, CD, or UC disease states. Imputed metagenome analysis indicated that these modules displayed distinct metabolic functionality, specifically the enrichment of oxidative response and glycan metabolism pathways relevant to host-pathogen interaction in the disease-associated modules. The highly preserved microbial modules accurately classified IBD status of individual patients during disease quiescence, suggesting that microbial dysbiosis in IBD may be an underlying disorder independent of disease activity. Microbial modules thus provide an integrative view of microbial ecology relevant to IBD.

Biological control in the microbiome era: Challenges and opportunities

“…This approach has already been used to gain a better understanding of and new insights into the functions of the human microbiome, and into its co-evolution with the hosts and their environment (Arumugam et al, 2011;Qin et al, 2010;Yatsunenko et al, 2012). For example, (Tong et al, 2013) identified groups of genes essential for life in the human gut that were conserved across functional microbial communities (e.g. carbohydrate and amino acid metabolism), whereas several virulent pathways (including bacterial invasion, pathogenic E. coli infection) were enriched in functional microbial communities associated with Inflammatory Bowel Syndrom.…”

“…A reference human gut metagenome was established by high-throughput sequencing (Qin et al, 2010), and comparative metagenomics between healthy controls and patients suffering from several disorders contributed to the characterization of a ''healthy microbiome'' (Greenblum et al, 2011;Qin et al, 2010;Tong et al, 2013). Interventional studies are also useful in defining a ''healthy'' microbiota, since changes in the microbial community induced by prebiotics, dietary interventions or pathogen infection can be studied in relation to clinical improvement or worsening.…”

Dysbiosis of the Gut Microbiota on the Inflammatory Background due to Lack of Suppressor of Cytokine Signalling-1 in Mice

“…Several studies have indicated that IBD patients have dysbiosis, in which taxa in the phylum Firmicutes are consistently decreased and taxa in phylum Proteobacteria are increased [35-37]. In addition, some immunocompromised mice show a high correlation between colitis and dysbiosis.…”

IBD: Microbiota Manipulation through Diet and Modified Bacteria

“…Both quantitative and qualitative changes in the faecal microbiota have been reported in IBD, particularly a reduced biodiversity in comparison to healthy controls [11]. The gastrointestinal microbiome of healthy humans is predominated by members of the phyla Firmicutes and Bacteroidetes, whilst IBD is associated with a dysbiosis mainly characterised by a lower proportion of Firmicutes, as well as an increase in bacteria from the Proteobacteria phylum [12,13]. It is likely, though, that much of the reduction in diversity is secondary to inflammation, as similar changes are seen in a number of animal models including dextran sodium sulphate-induced colitis and Citrobacter rodentium -induced colitis [14].…”