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

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.