S10.3c Clinical studies provide new insights on the association between the microbiota and host resistance to Candida albicans intestinal colonization
Authors: Delavy Margot , Burdet Charles , Sertour Natacha , Chatelier Emmanuelle Le , Doquier Jean-Denis , Volant Stevenn , Ghozlane Amine , Grall Nathalie , Duval Xavier , Mentré France , Duffy Darragh , D'Enfert Christophe , Bougnoux Marie-Elisabeth 
Published: September 2022

Abstract

S10.3 The mycobiome characterization: future perspectives or just a trend?, September 24, 2022, 10:30 AM - 12:00 PM

Objectives
Candida albicans is both a harmless commensal intestinal yeast in healthy individuals and a harmful opportunistic pathogen in immunocompromised patients, causing life-threatening invasive candidiasis. C. albicans intestinal overgrowth is a prerequisite for intestinal translocation, which is at the root of invasive candidiasis. Therefore, to prevent invasive candidiasis in immunocompromised patients, it is necessary to curb intestinal C. albicans overgrowth. However, little is known of the role of bacterial species of the microbiota in dampening C. albicans intestinal colonization.
We aimed to decipher the influence of the bacterial and fungal intestinal microbiota on C. albicans gut colonization in healthy individuals in whom their microbiota was modified or not by antibiotic treatment.

Methods
We studied two cohorts of healthy individuals: the first cohort included 22 volunteers for which fecal samples were collected before, during and after a 3-day regimen of third-generation cephalosporin antibiotics. The second cohort gathered 1000 healthy individuals for which a single fecal sample was collected. We quantified C. albicans carriage using a specific quantitative PCR approach. We monitored the antibiotic effect on the composition of the fungal microbiota—the so called mycobiota—in the gut of the individuals up to 180 days post-antibiotic exposure, using both the qPCR data and ITS1 targeted metagenomic. We also monitored the level of fecal β-lactamase activity, which is known to modulate the intensity of post-cephalosporin intestinal dysbiosis. Finally, to identify potential C. albicans inhibiting bacteria, we used MaAsLin2 to search for associations between C. albicans levels and bacterial species abundance, deduced from shotgun metagenomics data obtained from all individuals and annotated at the species level.

Results
A very high level of C. albicans carriage was observed in both cohorts, with a prevalence of 95.2% and 83.1% in the first and second cohort, respectively. Yet, the quantity of C. albicans DNA detected varied greatly between subjects. The mycobiota composition was significantly altered by antibiotics and the fungal load was increased both at short and long term. Particularly, C. albicans abundance was increased but with wide inter-subject variations. A part of these variations was explained by changes in the levels of endogenous fecal β-lactamase activity, with subjects characterized by a low increase of β-lactamase activity displaying a higher increase of C. albicans levels. Finally, using shotgun metagenomics data, we identified a first set of 50 bacterial and archaeal species whose abundance inversely correlated with C. albicans abundance.

Conclusion
These results (1) bring a new understanding of C. albicans overgrowth in healthy individuals, (2) lead to the identification of microbial signatures with a potential key role in controlling C. albicans gut colonization, and finally (3) show for the first time that changes in endogenous fecal β-lactamase activity is a key factor for C. albicans overgrowth in the gut after antibiotic exposure. Taken together, these results open the way for new intervention strategies to curb C. albicans intestinal overgrowth.