Shifts in the gut microbiota of inflammatory bowel disease patients in a longitudinal study

Erin McClure (1), Mitchell Dunklebarger (1), Kent Li (2), Jonas Halfvarsson (3), Curt Tysk (3), Daniel McDonald (4), Yoshiki Vázquez Baeza (4), William Walters (4), Rob Knight (4), Janet K. Jansson (2,5), Regina Lamendella (1,2)

(1) Juniata College, Huntingdon, PA; (2) Lawrence Berkeley National Laboratory, Berkeley, CA; (3) Orebro University Hospital, Orebro, SE; (4) University of Colorado Boulder; Boulder, CO; (5) Joint Genome Institute, Walnut Creek, CA


Background:The incidence of inflammatory bowel disease (IBD), a chronic inflammatory condition of the gastrointestinal tract, has been increasing in industrialized nations. Ulcerative colitis (UC) and Crohn’s disease (CD) are the two main subtypes of IBD. The etiology of IBD is unknown, however dysbiosis, or a shift, in the gut microbial community structure has been observed in IBD patients. A dysregulated immune response to the commensal gut microbiota has been implicated in IBD pathogenesis. It remains unknown whether this dysbiosis causes or is a result of this aberrant immune response. The aim of this study is to track the microbial community dynamics of IBD patients over multiple time points to better correlate disease condition with the status of the gut microbiota.
Methods:This is the first longitudinal study of dysbiosis in IBD patients, with a total of 692 samples taken from a cohort of IBD patients and healthy controls. Samples from between four and six timepoints were taken from 74 members of the IBD cohort (5 healthy controls, 43 UC, 3 collagenous colitis, 1 lymphocytic colitis, 11 colonic CD, 6 terminal CD, and 6 ileal CD) to yield 363 samples. The QIIME pipeline was used to analyze the 250 million 16S rRNA reads obtained using the Illumina iTAG sequencing platform. Sequences were clustered with Uclust Ref and annotated using the Greengenes database. The cumulative abundance of top 20 phyla and families were determined for each sample, and the data were clustered by non-metric multidimensional scaling (nMDS) in PC-ORD. Temporal barcharts were created to visualize dysbiosis overtime.
Results: Prevotellaecae dominate the gut microbiota in healthy individuals. Temporal shifts in the relative abundance of Bacteroides have been observed in some CD patients with multiple time points. Overall instability is seen in CD patients compared to UC and healthy controls. The nMDS shows a possible spectrum of dysbiosis in IBD, as healthy timepoints clustered with predicted non-flare up timepoints in IBD.  


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