Gut associated metabolites and their roles in Clostridioides difficile pathogenesis

Abstract

The nosocomial pathogen Clostridioides difficile is a burden to the healthcare system. Gut microbiome disruption, most commonly by broad-spectrum antibiotic treatment, is well established to generate a state that is susceptible to CDI. A variety of metabolites produced by the host and/or gut microbiota have been shown to interact with C. difficile . Certain bile acids promote/inhibit germination while other cholesterol-derived compounds and amino acids used in the Stickland metabolic pathway affect growth and CDI colonization. Short chain fatty acids maintain intestinal barrier integrity and a myriad of other metabolic compounds are used as nutritional sources or used by C. difficile to inhibit or outcompete other bacteria in the gut. As the move toward non-antibiotic CDI treatment takes place, a deeper understanding of interactions between C. difficile and the host’s gut microbiome and metabolites becomes more relevant.

The cell wall lipoprotein CD1687 acts as a DNA binding protein during deoxycholate-induced biofilm formation inClostridioides difficile

“…During an infection, pathogens encounter several environmental factors including the presence of antibiotics, bile salts, osmotic pressure and varying nutrient sources and these are known to be important signals for biofilm formation during colonization (18,19). Interestingly, C. difficile would face different challenges during dysbiosis as it changes of the nutritional environment, bile salt metabolism, and osmotic and oxidative/nitrosative stresses, (20). Any of these factors could induce biofilm formation.…”

Gut microbiota and microbiota-based therapies for Clostridioides difficile infection

“…Clostridioides difficile spores require a germinant to transform from the spore state to the growing, vegetative cell, in the form of specific bile acids. Primary bile acids are synthesized by hepatocytes and transformed into secondary bile acids by certain members of the healthy gut microbiota ( 28 , 41 ). Bile acids derived from cholic acid promote the germination of C. difficile spores, while bile acids derived from chenodeoxycholic acid (CDCA) inhibit germination ( 41 ).…”

“…Primary bile acids are synthesized by hepatocytes and transformed into secondary bile acids by certain members of the healthy gut microbiota ( 28 , 41 ). Bile acids derived from cholic acid promote the germination of C. difficile spores, while bile acids derived from chenodeoxycholic acid (CDCA) inhibit germination ( 41 ). In addition, vegetative cell growth of C. difficile is inhibited by CDCA.…”

“…In addition, vegetative cell growth of C. difficile is inhibited by CDCA. In animal studies and in humans, hosts with higher levels of secondary bile acids were more resistant to developing CDI, whereas hosts with higher levels of primary bile acids were more susceptible ( 41 ).…”

Editorial: the acid test—can bile acids predict recurrence of Clostridioides difficile infection? Authors' reply

“…While we focused upon BAs, recent studies highlight a more prominent role for other gut microbial metabolites in CDI than was previously recognised, with one particular focus being the contribution of coprostanol and amino acids via the Stickland pathway. 8,9 There remains a clear clinical need for biomarkers predicting recurrence in primary CDI. Faecal microbiota transplant (FMT) post-vancomycin effectively reduces recurrence risk after a first or second CDI episode (rather than its historical use after multiple recurrences).…”