September 30, 2021

Molecular imaging of C. diff infection

C. difficile — the leading cause of hospital-associated intestinal infections — induces a rapid influx of bile acids into the gut, which could provide a novel target for blocking infection.

Disruption of the gut microbiota, for example by antibiotics, allows the bacterium Clostridioides difficile (C. diff) to colonize and cause disease. C. diff is the leading cause of hospital-associated intestinal infections in the U.S., but the mechanisms of colonization are unclear. 

Eric Skaar, PhD, Jeffrey Spraggins, PhD, and colleagues used imaging mass spectrometry, a molecular imaging technique, to explore how C. diff impacts the gut environment in an animal model of infection. 

They found that C. diff induces a rapid influx into the gut of bile acids, compounds produced in the liver that aid in the absorption of fats and vitamins. Administration of cholestyramine, a drug that sequesters bile acids, delayed colonization and reduced germination (which is required for C. diff production of disease-causing toxins). 

The findings, published in Cell Reports, support a role for bile acids in C. diff germination and suggest that modulating access to bile acids may disrupt the ability of C. diff to colonize and cause disease.

Aaron Wexler, PhD, and Emma Guiberson are co-first authors of the Cell Reports paper. The research was supported by the National Institutes of Health (grants AI073843, AI045992, AI038581, DK058404, EB001628), Helen Hay Whitney Foundation, and American Heart Association.