The prevalence and transcriptional activity of the mucosal microbiota of ulcerative colitis patients

Abstract

Active microbes likely have larger impact on gut health status compared to inactive or dormant microbes. We investigate the composition of active and total mucosal microbiota of treatment-naïve ulcerative colitis (UC) patients to determine the microbial picture at the start-up phase of disease, using both a 16S rRNA transcript and gene amplicon sequencing. DNA and RNA were isolated from the same mucosal colonic biopsies. Our aim was to identify active microbial members of the microbiota in early stages of disease and reveal which members are present, but do not act as major players. We demonstrated differences in active and total microbiota of UC patients when comparing inflamed to non-inflamed tissue. Several taxa, among them the Proteobacteria phyla and families therein, revealed lower transcriptional activity despite a high presence. The Bifidobacteriaceae family of the Actinobacteria phylum showed lower abundance in the active microbiota, although no difference in presence was detected. The most abundant microbiota members of the inflamed tissue in UC patients were not the most active. Knowledge of active members of microbiota in UC patients could enhance our understanding of disease etiology. The active microbial community composition did not deviate from the total when comparing UC patients to non-IBD controls.

Figure 1

Alpha diversity in inflamed and non-inflamed tissue. Distribution of alpha diversity in the inflamed and non-inflamed samples from UC patients and control patients, showing (a) the DNA and (b) the RNA datasets, and (c) a scatterplot of the alpha diversity in the paired RNA and DNA samples, with the average alpha diversity on the x-axis and the difference on the y-axis.

Figure 2

UniFrac distances between different diagnosis groups and datasets. PCoA plot for (a) the DNA dataset and (b) the RNA dataset. Each sample is coloured according to the disease status and inflammation status. The black lines connect the samples from the same patient. c) PCoA plot of a combined analysis from both the DNA and RNA dataset. Paired RNA-DNA samples are connected with black lines.

Figure 3

Average log transformed abundances of bacterial families in the total and active microbiota. The diagonal line indicates identical abundances in the DNA and RNA datasets. The colour intensity shows how much the abundance of the bacterial families correlate.

Figure 4

Bacterial taxonomic family abundances in total and active microbiota in all the samples. The three families Ruminococcaceae, Lachnospiraceae and Bacteroidaceae dominated in both datasets.

Figure 5

Distribution of total and active microbiota abundances across disease and inflammation status. A subset of the most prevalent and active bacterial families.