Candida albicans colonization in the human colon correlates with a reduction in acetate- and butyrate-producing bacteria, as simulated using the M-SHIME® model.

Candida albicans is a common gut commensal, typically restricted by the resident microbiota. However, microbiome disruption can enable its outgrowth, increasing the risk of life-threatening candidiasis. Restoring key protective microbes offer a therapeutic strategy, though their identification remains challenging. Using the M-SHIME® model simulating the human proximal colon, we investigated C. albicans-bacteriome interactions under eubiotic and dysbiotic conditions. We assessed how clindamycin, ciprofloxacin, and metronidazole modulate C. albicans colonization and evaluated associated microbial and metabolic shifts. The effects were antibiotic- and donor-specific: clindamycin facilitated colonization, ciprofloxacin had no impact, and metronidazole showed variable outcomes. Engraftment did not correlate with total bacterial concentration or α-diversity, but with the loss of specific taxa, notably Lachnospiraceae and Bifidobacterium. These correlations were supported functionally by reductions in acetate and butyrate, suggesting a metabolic mechanism of fungal suppression. This study highlights the role of dysbiosis in C. albicans outgrowth and supports targeted microbiome restoration strategies.