The relevance of spatial composition in the microbial changes associated with ulcerative colitis, is unclear. We coupled luminal brush samples, mucosal biopsies and laser capture microdissection with deep sequencing of the gut microbiota to develop an integrated spatial assessment of the microbial community in health and ulcerative colitis.

The relevance of spatial composition in the microbial changes associated with ulcerative colitis, is unclear. We coupled luminal brush samples, mucosal biopsies and laser capture microdissection with deep sequencing of the gut microbiota to develop an integrated spatial assessment of the microbial community in health and ulcerative colitis. A total of 97 samples were sequenced to a mean depth of 31,642 reads from nine individuals, four healthy volunteers undergoing routine colonoscopy and five patients undergoing surgical colectomy for medically-refractory ulcerative colitis. Samples were retrieved at four colorectal locations, incorporating the luminal microbiota, the mucus gel layer and whole mucosal biopsies. Inter-personal variability accounted for approximately half of the total variance. Surprisingly, within individuals, Asymmetric Eigenvector Map analysis demonstrated differentiation between the luminal and mucus gel microbiota, in both health and ulcerative colitis, with no differentiation between colorectal regions. At a taxonomic level, differentiation was evident between both cohorts, as well as between the luminal and mucosal compartments, with a small group of taxons uniquely discriminating the luminal and mucosal microbiota in colitis. There was no correlation between regional inflammation and a breakdown in this spatial differentiation or bacterial diversity. Our study demonstrates a conserved spatial structure to the colonic microbiota, differentiating the luminal and mucosal communities, within the context of marked inter-personal variability. While elements of this structure overlap between health and UC, there are differences between the two groups, both in terms of the overall taxonomic composition and how spatial structure is ascribable to distinct taxons.