Veillonella intestinal colonization promotes C. difficile infection in Crohn's disease

Abstract

Crohn's disease is a severe inflammatory disorder of the intestine for which there is no cure. Individuals suffering from Crohn's disease are at an increased risk of developing Clostridioides difficile infection (CDI), which considerably exacerbates symptoms. Using a prospective observational clinical study combined with animal models of intestinal inflammation, we show that intestinal colonization by Veillonella, an oral commensal, promotes CDI in Crohn's disease. In mice, Veillonella parvula suppresses expression of the main bile acid transporter, ASBT, thus preventing bile acid reabsorption. Similarly, Veillonella abundance is associated with increased bile acid metabolism in Crohn's disease patients. This increase in bile acid availability within the intestinal lumen triggers C. difficile germination. V. parvula expresses a highly pro-inflammatory lipopolysaccharide that triggers the transcription factors c-Jun and c-Fos regulating ASBT expression. These findings highlight that oral commensals can exacerbate intestinal disease, providing pathways to design therapeutics to treat CDI in Crohn's disease patients.

Keywords: ASBT; Clostridioides difficile; Crohn's disease; Veillonella parvula; pathogenesis; spore germination.