title: 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.
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Maomeng
authors.initials: M
authors.lastname: Tong
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Li
authors.forename: Laura
authors.initials: L
authors.lastname: Wegener Parfrey
authors.forename: Bennett
authors.initials: B
authors.lastname: Roth
authors.forename: Andrew
authors.initials: A
authors.lastname: Ippoliti
authors.forename: Bo
authors.initials: B
authors.lastname: Wei
authors.forename: James
authors.initials: J
authors.lastname: Borneman
authors.forename: Dermot P B
authors.initials: DP
authors.lastname: McGovern
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Frank
authors.forename: Ellen
authors.initials: E
authors.lastname: Li
authors.forename: Steve
authors.initials: S
authors.lastname: Horvath
authors.forename: Rob
authors.initials: R
authors.lastname: Knight
authors.forename: Jonathan
authors.initials: J
authors.lastname: Braun
mesh_terms: D016000:Cluster Analysis; D015331:Cohort Studies; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000209:etiology / Q000382:microbiology*; D007413:Intestinal Mucosa / Q000382:microbiology* / Q000473:pathology; D054892:Metagenome; D064307:Microbiota; D010641:Phenotype; D012336:RNA, Ribosomal, 16S
chemical_list: D012336:RNA, Ribosomal, 16S