Proteus mirabilis a key bacterium associated with Crohn’s disease

Proteus mirabilis is significantly more prevalent in the faeces and gut mucosa of patients with Crohn’s disease (CD) than in healthy individuals and plays a crucial role in CD pathogenesis, researchers from the Chinese University of Hong Kong (CUHK) have shown.

The researchers analyzed faecal samples from 54 patients with CD and 54 healthy controls. “Results showed a significantly higher prevalence of Proteus spp. in faecal samples from patients with CD vs healthy controls, at 18.5 percent vs 5.6 percent [p<0.05],” reported Professor Siew-Chien Ng of the Department of Medicine and Therapeutics, CUHK. [Gastroenterology 2021;160:317-330]

Proteus spp. was also significantly more abundant in colonic biopsies obtained from 67 patients with CD compared with those from 40 healthy controls (noninflamed CD, p<0.01; inflamed CD, p<0.001).

“The high Proteus patient group had significantly higher CD activity index scores compared with the low Proteus group [p<0.05], suggesting that patients with a greater relative abundance of Proteus spp. might be afflicted with more severe CD activity,” the researchers noted.

Among CD patients with high abundance of Proteus spp., the abundance of Fusobacterium was significantly increased, while the abundance of Faecalibacterium was significantly decreased (both p<0.05).

Notably, all 24 Proteus isolates recovered from patients with CD belonged to the P. mirabilis lineage. Further studies in animal models showed that P. mirabilis colonization promoted colonic inflammation by inducing proinflammatory pathways and promoting secretion of proinflammatory cytokines, suggesting that P. mirabilis plays a crucial role in CD pathogenesis.

Findings of this study, as part of the Eastern Inflammatory Bowel Disease Gut Microbiota (ENIGMA) project, suggest that P. mirabilis may be regarded as a diagnostic and therapeutic target to improve CD recovery and remission, the researchers noted.

“Another recent study under the ENIGMA project showed that patients with CD were more likely to have consumed ultra-processed food in early life compared with healthy adults,” said Ng. “This may be a trigger for CD.”

“In addition, patients with CD are found to have higher annual intake of food additives, including emulsifiers, compared with their immediate family members,” she continued. “This is likely to have an unfavourable effect on gut microbiota and may serve as a driver of ongoing inflammation.”

“These findings suggest that modulation of gut microbiota may play a role in prevention and treatment of CD,” she added.

The global rise in incidence of inflammatory bowel disease (IBD) highlights a pressing need to identify and manage risk factors as well as to develop new therapies for patients. With a USD 2 million grant recently received from The Leona M. and Harry B. Helmsley Charitable Trust, researchers at CUHK will collaborate with those from the University of Calgary in the Global IBD Visualization of Epidemiology Studies in the 21st Century (GIVES-21) project to define the epidemiology of IBD and identify environmental risk factors in 29 newly industrialized countries in Asia, South America and Africa.

“Data collected from the GIVES-21 project will be built into an open-access interactive online map, and will help inform governments in the formulation of healthcare policies to address the rising threat of IBD,” said Dr Joyce Mak of the Department of Medicine and Therapeutics, CUHK.