Pre-colonization with the commensal fungusCandida albicansreduces murine susceptibility toClostridium difficileinfection

Abstract

Clostridium difficile is a major nosocomial pathogen responsible for close to half a million infections and 27,000 deaths annually in the U.S. Preceding antibiotic treatment is a major risk factor for C. difficile infection (CDI) leading to recognition that commensal microbes play a key role in resistance to CDI. Current antibiotic treatment of CDI is only partially successful due to a high rate of relapse. As a result, there is interest in understanding the effects of microbes on CDI susceptibility to support treatment of patients with probiotic microbes or entire microbial communities (e.g., fecal microbiota transplantation). The results reported here demonstrate that colonization with the human commensal fungus Candida albicans protects against lethal CDI in a murine model. Colonization with C. albicans did not increase the colonization resistance of the host. Rather, our findings showed that one effect of C. albicans colonization was to enhance a protective immune response. Mice pre-colonized with C. albicans expressed higher levels of IL-17A in infected tissue following C. difficile challenge compared to mice that were not colonized with C. albicans. Administration of cytokine IL-17A was demonstrated to be protective against lethal murine CDI in mice not colonized with C. albicans. C. albicans colonization was associated with changes in the abundance of some bacterial components of the gut microbiota. Therefore, C. albicans colonization altered the gut ecosystem, enhancing survival after C. difficile challenge. These findings demonstrate a new, beneficial role for C. albicans gut colonization.

Therapeutic administration of the recombinant antimicrobial peptide microcin J25 effectively enhances host defenses against gut inflammation and epithelial barrier injury induced by enterotoxigenic Escherichia coli infection

“…[78][79][80] To better understand the therapeutic phenotype, we assayed the MccJ25 gut microbiota composition in vivo. [78][79][80] To better understand the therapeutic phenotype, we assayed the MccJ25 gut microbiota composition in vivo.…”

The Gut-Lung Axis in Health and Respiratory Diseases: A Place for Inter-Organ and Inter-Kingdom Crosstalks

“…The most appropriate approach to decipher the role of gut microbiota is therefore considering the gut as an ecosystem in which inter-kingdom interactions occur and have major implications as suggested by the significant correlations between the gut bacteriobiota and mycobiota profiles among healthy subjects (Hoffmann et al, 2013). Yeasts, e.g., Saccharomyces boulardii and C. albicans, or fungus wall components, e.g., β-glucans, are able to inhibit the growth of some intestinal pathogens (Zhou et al, 2013;Markey et al, 2018). S. boulardii also produces proteases or phosphatases that inactivate the toxins produced by intestinal bacteria such as Clostridium difficile and Escherichia coli (Castagliuolo et al, 1999;Buts et al, 2006).…”

Clostridium species as probiotics: potentials and challenges

“…C. difficile C. difficile infection often occurs after antibiotics therapy [54][55][56]. Antibiotics can eliminate part of commensal bacteria in gut and then the opportunistic C. difficile breeds crazily dues to imbalance between microbiota and intestinal immune system.…”