Sinergia: Bacteria-host interactions through bile acid transforming bacteria 

The anaerobic, endospore-forming bacterium Clostridioides difficile is the leading cause of nosocomial antibiotic-associated diarrhoea and places a significant burden on healthcare providers. Symptoms of C. difficile infection (CDI) range from non-symptomatic colonisation to mild, self-limited diarrhoea to severe pseudomembranous colitis and toxic megacolon. CDI transmission occurs via inadvertent ingestion of C. difficile spores which are highly resilient and capable of withstanding exposure to oxygen and a wide range of chemical and physical agents. Disease progression is entirely dependent on the germination of these persistent endospores, which generates the vegetative cells capable of producing toxins A and B, the main virulence factors of C. difficile associated disease (CDAD).


Only recently have we begun to elucidate the mechanisms of C. difficile spore germination and the importance of bile salts in regulating this process. Bile is excreted by the liver and facilitates the absorption of lipids and lipid-soluble vitamins. Some of this bile enters the gastrointestinal tract where it is transformed from primary bile salts into secondary bile salts by 7-dehydroxylating gut bacteria. Whilst primary bile salts trigger C. difficile spore germination, secondary bile salts have been shown to inhibit germination and/or the outgrowth of these spores. Hence, a model is proposed in which broad-spectrum antibiotic treatment leads to a dysbiosis of the gut microbiome and predisposes to CDI.


This project funded by a Sinergia grant from the Swiss National Science Foundation forms a collaboration between the SBRC-Nottingham and research groups at EPFL-Lausanne and the University of Bern in Switzerland. This international, interdisciplinary collaboration brings together expertise in the fields of clostridial genetics, specialist mouse models and bile acid analysis to ascertain the precise role of bile acid transforming bacteria in intestinal infection.