Alteration in Urease-producing Bacteria in the Gut Microbiomes of Patients with Inflammatory Bowel Diseases

Abstract

Abstract Background and Aims Bacterial urease is a major virulence factor of human pathogens, and murine models have shown that it can contribute to the pathogenesis of inflammatory bowel diseases [IBD]. Methods The distribution of urease-producing bacteria in IBD was assessed using public faecal metagenomic data from various cohorts, including non-IBD controls [n = 55], patients with Crohn’s disease [n = 291] or ulcerative colitis [n = 214], and patients with a pouch [n = 53]. The ureA gene and the taxonomic markers gyrA, rpoB, and recA were used to estimate the percentage of urease producers in each sample. Results Levels of urease producers in patients with IBD and non-IBD controls were comparable. In non-IBD controls and most IBD patients, urease producers were primarily acetate-producing genera such as Blautia and Ruminococcus. A shift in the type of the dominant urease producers towards Proteobacteria and Bacilli was observed in a subset of all IBD subtypes, which correlated with faecal calprotectin levels in one cohort. Some patients with IBD had no detectable urease producers. In patients with a pouch, the probiotic-associated species Streptococcus thermophilus was more common as a main urease producer than in other IBD phenotypes, and it generally did not co-occur with other Bacilli or with Proteobacteria. Conclusions Unlike all non-IBD controls, patients with IBD often showed a shift towards Bacilli or Proteobacteria or a complete loss of urease production. Probiotics containing the species S. thermophilus may have a protective effect against colonisation by undesirable urease-producing bacteria in a subset of patients with a pouch.