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).

Genetic characterisation of Campylobacter concisus: Strategies for improved genomospecies discrimination

“…The Welch two-sample t-test of the G+C contents generated a very low p-value (<0.001) confirming that the two GS have statistically different G+C contents. These differences in G+C content between GS1 and GS2 are consistent with those reported in the literature [72,73]. Larsen, Cosentino, Lukjancenko, Saputra, Rasmussen, Hasman, Sicheritz-Ponten, Aarestrup, Ussery and Lund [74] compared the ability of SpeciesFinder, rMLST, TaxonomyFinder and KmerFinder to predict species identification of assembled draft or complete genomes from 695 isolates representing the bacterial diversity known at the time.…”

“…Later studies found no significant differences between GS and disease [3,8,80] but associations between GS and isolation site were reported [7,80]. More recent studies have also reported associations between disease and GS [81] or GS subgroups [72]. Although assignment of isolates to GS may not provide a clear indication of virulence potential, it does provide more complete taxonomic information that, if collected routinely, may contribute to a more complete picture of the role of C. concisus GS in various human diseases.…”

Campylobacter concisus gastritis masquerading as Helicobacter pylori on gastric biopsy

“…3 C. concisus is part of the normal human oral flora and is emerging as a potential pathogen within the intestinal tract. [3][4][5][6] Reports in the literature have associated C. concisus with gastroenteritis, 7-10 inflammatory bowel disease, 11,12 microscopic colitis, 13,14 and inflammation associated with Barrett's esophagus. 15 Ours is the first report linking the identification of…”

Microscopic colitis: Etiopathology, diagnosis, and rational management

“…The pathogenesis of microscopic colitis is still poorly elucidated, but it is likely a result of dysbalanced immune response involving epithelial dysfunction ( Barmeyer et al, 2017 ), collagen metabolism, secretory diarrhea ( Escudero-Hernández et al, 2020 ), and microbiota ( Khalili et al, 2021 ; Aagaard et al, 2021 ; Figure 2 ), combined with the risk factors mentioned above in genetically predisposed individuals ( Ianiro et al, 2012 ). This complex area has previously been extensively covered by others ( Zabana et al, 2022 ; Liu and Chen, 2022 ; Miehlke et al, 2019 ), and we therefore focused on new data in the fields of microbiota, genetic susceptibility, and SARS-CoV2.…”

“…A. muciniphila adheres to the intestinal epithelium and strengthens enterocyte monolayer integrity in vitro, suggesting that a reduction may cause intestinal barrier dysfunction ( Reunanen et al, 2015 ). More recently, a team of researchers found a higher long-term risk of developing microscopic colitis in patients whose stool carried Campylobacter concisus ( Aagaard et al, 2021 ; Nielsen et al, 2020 ). Campylobacter concisus is a commensal of the human oral microbiota, which occasionally may be isolated from stool samples.…”