Starting Over to Treat Crohn's Disease

New work on mouse models suggests that a fresh approach to re-engineering the gut microbiome may yield an effective treatment for Crohn’s disease. Researchers from the Perelman School of Medicine at the University of Pennsylvania have isolated a single bacterial enzyme, known as urease, which is responsible for an imbalance in the gut microbiome or dysbiosis, that aggravates Crohn’s disease and other inflammatory conditions. They suggest that eliminating most of the bacteria in the microbiome, followed by re-introduction of a specific “good” bacteria that is absent in this enzyme may be an effective means of treatment. Senior author Gary Wu, MD, associate chief for research in the division of Gastroenterology, commented, “Because it’s a single enzyme that is involved in this process, it might be a targetable solution. The idea would be that we could ‘engineer’ the composition of the microbiota in some way that lacks this particular one.” The findings were published online last week in Science Translational Medicine.

The research investigated the role of nitrogen metabolism in dysbiosis using a series of human and mouse studies. The team reported that a bacteria type that harbors the urease enzyme converts urea into ammonia that, when reabsorbed, makes amino acids that are associated with dysbiosis. By erasing the microbiome slate in mice using antibiotics and polyethylene glycol, the team were able to introduce and propagate a new bacterial species, E. coli, that could be tailored to be either urease-negative or urease-positive. Mice injected with the urease-negative variety did not lead to dysbiosis, while mice injected with urease-positive E. coli did. This suggests that it may be feasible to alter the composition of gut microbiota in human patients with inflammatory bowel disease including Crohn’s. Dr. Wu stated, “The outcomes of this study and the analysis of collected biospecimens will be an important first step in building a technology platform to engineer a beneficial composition of the gut microbiota for the treatment of inflammatory bowel diseases.”

Read a news story about the research findings.

The journal abstract may be read here.