Candida gut colonization, yeast species distribution, and biofilm production in Clostridioides difficile infected patients: a comparison between three populations in two different time periods

Grazia Brunetti,Flavia Raponi,Libenzio Adrian Conti,Giammarco Raponi,Alessandro Giuliani,Camilla Paradisi,Anna Sara Navazio

doi:10.1007/s42770-021-00512-4

Abstract

Candida gut colonization and yeast biofilm production capacity were investigated, by means of XTT reduction assay, in Clostridioides difficile infected (CDI) patients, in non-CDI diarrheic patients, and in healthy donors in two different time periods (2013–2015 and 2018–2019 respectively). Candida gut colonization was significantly (p < 0.001) associated to C. difficile infection, and to patients infected with hypervirulent C. difficile strains bearing the tcdC deletion at nucleotide 117 (p = 0.0003). Although there was not a prevalent yeast species in CDI patients, C. albicans was the species significantly (p < 0.001) associated to both the infections sustained by the non-hypervirulent C. difficile strains and those caused by the hypervirulent strain (p = 0.001). The biofilm production by the yeasts isolated from the CDI patients and from non-CDI diarrheic patients did not differ significantly. However, a significantly (p = 0.007) higher biofilm production was observed in the Candida strains, particularly C. albicans, isolated from healthy donors compared to that of the yeasts cultured from CDI patients. Seasonal occurrence was observed in the isolation rate of CDI and non-CDI diarrheic cases (p = 0.0019), peaking in winter for CDI patients and in spring for non-CDI diarrheic patients. Furthermore, seasonality emerged in the gut colonization by Candida of CDI patients in the winter. It seems, therefore, that the reduced capacity of biofilm production by Candida strains isolated from CDI patients might have a role in the development of C. difficile infection, probably facilitating the spread of the bacteria into the gut thus amplifying their pathogenic action.

Highlights

Candida and Clostridioides difficile are two opportunistic pathogens residing in the human gut
The statistical analysis confirmed that the two studied temporal phases were homogeneous by the relative percentage of the number and age of patients’ distribution, the month of isolation, and the number of Candida strains tested for biofilm production capacity
Candida gut colonization accompanied symptomatic C. difficile infection (CDI), in particular those sustained by C. difficile strains bearing the tcdC deletion gene at nucleotide 117

Summary

Introduction

Candida and Clostridioides difficile are two opportunistic pathogens residing in the human gut. The virulence of C. albicans depends on the growth in yeast, pseudohyphal, and hyphal forms and to the capacity to survive in a biofilm state. The latter could be a phenomenon of paramount importance since the microenvironment of C. albicans biofilms can favor the growth of anaerobic microorganism such as Clostridium perfringens under normally toxic aerobic conditions [7]. We evidenced a link between CDI and Candida colonization of the gut [8]. Since the debate is still open, in this study, we investigated the differences in the Candida gut colonization of CDI patients, of non-CDI diarrheic patients, and of healthy donors in two different periods with different epidemiological CDI diffusion. We wanted to investigate whether the metabolically active biofilm production by Candida differed among strains isolated from the three study populations

Methods

Results

Discussion

Conclusion