Candida albicans colonization in the M-SHIME

Candida albicans primarily exists as a harmless commensal in the gastrointestinal tract of warm-blooded animals. In health, the microbiome restricts C. albicans colonization, but disruption of the microbial balance may lead to its outgrowth, which is a risk factor for life-threatening candidiasis. Thus, a novel approach to treat C. albicans infections includes the reintroduction into the impaired microbiome of the key microbes that initially reduced C. albicans growth. However, identifying these microbes remains challenging. Here, we used the SHIME model simulating the human proximal colon to investigate C. albicans-bacteriome interactions in eubiosis (commensal lifestyle) and dysbiosis (pathogenic lifestyle) states from an ecological standpoint. We compared the impact of three antibiotics, namely clindamycin, ciprofloxacin, and metronidazole, on C. albicans colonization. Our findings highlighted the role of specific bacterial taxa rather than the total bacteria concentration or bacteriome alpha-diversity. Disrupting the microbiome with antibiotics induced shifts in microbial composition which either facilitated C. albicans colonization (clindamycin) or not (ciprofloxacin) in an antibiotic-dependent manner. Intersubject variability was also observed (metronidazole). Correlating C. albicans levels and microbiome compositions revealed the particular role of the butyrate producers Lachnoclostridium and Agathobacter, but also of the acetate producers Bifidobacterium and Acidominococcus. Overall, our work lays the foundation for developing targeted biotherapeutics against opportunistic C. albicans outgrowth, advancing our comprehension of antibiotic-induced dysbiosis and its therapeutic implications. It calls for further investigations, and especially for supportive intervention studies.