The role of single and mixed biofilms in Clostridioides difficile infection and strategies for prevention and inhibition

Clostridioides difficile infection (CDI) is a serious disease with a high recurrence rate. The single and mixed biofilms formed by C. difficile in the gut contribute to the formation of recurrent CDI (rCDI). In parallel, other gut microbes influence the formation and development of C. difficile biofilms, also known as symbiotic biofilms. Interactions between members within the symbiotic biofilm are associated with the worsening or alleviation of CDI. These interactions include effects on C. difficile adhesion and chemotaxis, modulation of LuxS/AI-2 quorum sensing (QS) system activity, promotion of cross-feeding by microbial metabolites, and regulation of intestinal bile acid and pyruvate levels. In the process of C. difficile biofilms control, inhibition of C. difficile initial biofilm formation and killing of C. difficile vegetative cells and spores are the main targets of action. The role of symbiotic biofilms in CDI suggested that targeting interventions of C. difficile-promoting gut microbes could indirectly inhibit the formation of C. difficile mixed biofilms and improved the ultimate therapeutic effect. In summary, this review outlines the mechanisms of C. difficile biofilm formation and summarises the treatment strategies for such single and mixed biofilms, aiming to provide new ideas for the prevention and treatment of CDI.