Distinct gut microbiota profiles in patients with primary sclerosing cholangitis and ulcerative colitis

Abstract

Aim: To characterize the gut bacterial microbiota of patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC).

Methods: Stool samples were collected and relevant clinical data obtained from 106 study participants, 43 PSC patients with (n = 32) or without (n = 11) concomitant inflammatory bowel disease, 32 UC patients, and 31 healthy controls. The V3 and V4 regions of the 16S ribosomal RNA gene were sequenced on Illumina MiSeq platform to cover low taxonomic levels. Data were further processed in QIIME employing MaAsLin and LEfSe tools for analysis of the output data.

Results: Microbial profiles in both PSC and UC were characterized by low bacterial diversity and significant change in global microbial composition. Rothia, Enterococcus, Streptococcus, Veillonella, and three other genera were markedly overrepresented in PSC regardless of concomitant inflammatory bowel disease (IBD). Rothia, Veillonella and Streptococcus were tracked to the species level to identify Rothia mucilaginosa, Streptococcus infantus, S. alactolyticus, and S. equi along with Veillonella parvula and V. dispar. PSC was further characterized by decreased abundance of Adlercreutzia equolifaciens and Prevotella copri. Decrease in genus Phascolarctobacterium was linked to presence of colonic inflammation regardless of IBD phenotype. Akkermansia muciniphila, Butyricicoccus pullicaecorum and Clostridium colinum were decreased in UC along with genus Roseburia. Low levels of serum albumin were significantly correlated with enrichment of order Actinomycetales.

Conclusion: PSC is associated with specific gut microbes independently of concomitant IBD and several bacterial taxa clearly distinguish IBD phenotypes (PSC-IBD and UC).

Keywords: Dysbiosis; Gut microbiota; Inflammatory bowel disease; Primary sclerosing cholangitis; Ulcerative colitis.

Figure 1

Alpha diversity was consistently reduced in patients with ulcerative colitis as determined by Chao1 index, Shannon index and Simpson index. Groups labeled by the same letter (a, b) on the graph are not significantly different from each other (P < 0.05) as analyzed by ANOVA with Tuhey's post-hoc test.

Figure 2

Ordination plots shows a distinct clustering pattern of sampled bacterial communities, explained either by the liver damage (primary sclerosing cholangitis vs Healthy controls) (A) and by the intestinal inflammation (primary sclerosing cholangitis-inflammatory bowel disease vs ulcerative colitis) (B). Both graphs are based on unweighted Unifrac distance matrix and constructed by PERMANOVA. PSC: Primary sclerosing cholangitis; UC: Ulcerative colitis; IBD: Inflammatory bowel disease.

Figure 3

Median relative abundances of microbiota at order - level in all study subjects (A) and averaged for each study groups (B). We identified (mean ± SD) 40.83% ± 10.00% of sequences on the species level and 84.18% ± 6.83% of sequences on the genus level. PSC: Primary sclerosing cholangitis; UC: Ulcerative colitis; IBD: Inflammatory bowel disease.

Figure 4

Abundance of order Actinomycetales negatively correlates with serum albumin levels in the total study population.