High genetic diversity in Campylobacter concisus isolates from patients with microscopic colitis

Abstract

The emerging intestinal pathogen Campylobacter concisus has been associated with prolonged diarrhoea and classic inflammatory bowel diseases (IBD) and was recently also linked with microscopic colitis (MC). Previous reports have observed a high genetic diversity within isolates from diarrhoeic and IBD patients and from healthy controls (HC), and division of isolates into two major genomospecies (GS1 and GS2). The aim of this study was to describe genetic diversity in 80 recently cultivated MC biopsy and faecal isolates of C. concisus by multi-locus sequence typing (MLST); and to compare the phylogenetic relatedness to 102 isolates from diarrhoeic and IBD patients and HCs by k-mer-based distance estimation. MLST revealed high genetic diversity in MC isolates with 72 novel sequence types. K-mer divided MC isolates into two distinct clusters (cluster 1 n = 21, cluster 2 n = 49), with a significantly higher prevalence of cluster 2 isolates in biopsies than in faeces, p = 0.009. K-mer divided the 182 isolates into two major phylogenetic clusters: cluster 1 (GS1 isolates) and cluster 2 (GS2 isolates), which further differentiated into three subgroups. Cluster 1 and the three cluster 2 subgroups were each distinctive in mean genome size and GC count. Isolates from all disease phenotypes were present in cluster 1 and cluster 2 subgroup 2 and 3, whereas cluster 2 subgroup 1 only contained isolates restricted to patients with ulcerative colitis (n = 10) and HC (n = 4).

Keywords: Campylobacter concisus; Genetic diversity; Genomospecies; Inflammatory bowel disease; Microscopic colitis; Multi-locus sequence typing; Phylogenetic relatedness.

Fig. 1

Circular tree based on k-mer distance estimation of MC isolates revealed two distinct clusters with cluster 1 (GS1) (n = 21) and cluster 2 (GS2) (n = 59). Twenty faecal isolates (triangles) were divided equally into cluster 1 and 2 (n = 10 in each cluster), which was significantly different from the 60 biopsy isolates (squares) that mainly belonged to cluster 2 (n = 49). No significant differences in cluster differentiation were observed in isolates from CC patients (red colour) (cluster 1 n = 17 and cluster 2 n = 38) and from LC patients (green colour) (cluster 1 n = 4 and cluster 2 n = 21)