The role of inflammation in temporal shifts in the inflammatory bowel disease mucosal microbiome

Abstract

Studies of the human intestinal microbiome in patients with inflammatory bowel disease (IBD) consistently show that there are differences (an abnormal or unbalanced microbiome, “dysbiosis”) when compared to healthy subjects. We sought to describe changes in the microbiome in individual patients over time, and determine the clinical factors that are associated with significant alteration. Forty-two mucosal biopsies were collected from 20 patients that were spaced an average of 2.4 years apart. These were analysed using bacterial 16S rRNA gene high-throughput sequencing methods. Presence of active inflammation was determined endoscopically and histologically. Inferred metagenomics analysis was conducted using the PICRUSt package. We found that the differences in the microbiome over time in individual patients were greatest in the presence of ongoing intestinal inflammation, as determined by the Yue and Clayton theta distance between sample pairs (adjusted p = 0.00031). Samples from patients with previous abdominal surgery had lower alpha (within sample) diversity compared with those with no prior operations (mean Shannon index 2.083, 2.510 respectively, p = 0.017). There were no changes in the inferred bacterial metagenomic profile. The microbiome in IBD undergoes considerable fluctuation over time. These changes are greatest when there is histologically confirmed inflammation at both time-points.