5-ASA can functionally replace Clostridia to prevent a post-antibiotic bloom ofCandida albicansby maintaining epithelial hypoxia

Abstract

Antibiotic prophylaxis sets the stage for an intestinal bloom ofCandida albicans, which can progress to invasive candidiasis in patients with hematologic malignancies. Commensal bacteria can reestablish microbiota-mediated colonization resistance after completion of antibiotic therapy, but they cannot engraft during antibiotic prophylaxis. Here we use a mouse model to provide a proof of concept for an alternative approach, which replaces commensal bacteria functionally with drugs to restore colonization resistance againstC. albicans. Streptomycin treatment, which depletes Clostridia from the gut microbiota, disrupted colonization resistance againstC. albicansand increased epithelial oxygenation in the large intestine. Inoculating mice with a defined community of commensal Clostridia species reestablished colonization resistance and restored epithelial hypoxia. Notably, these functions of commensal Clostridia species could be replaced functionally with the drug 5-aminosalicylic acid (5-ASA), which activates mitochondrial oxygen consumption in the epithelium of the large intestine. When streptomycin-treated mice received 5-ASA, the drug reestablished colonization resistance against C. albicans and restored physiological hypoxia in the epithelium of the large intestine. We conclude that 5-ASA treatment is a non-biotic intervention that restores colonization resistance against C. albicans without requiring the administration of live bacteria.

Meeting report ‘Microbiology 2023: from single cell to microbiome and host’, an international interacademy conference in Würzburg

“…Notably, increased epithelial oxygenation after Clostridia depletion drove a postantibiotic C. albicans expansion. Commensal Clostridia species could be replaced functionally with 5-aminosalicylic acid (5-ASA), which activated mitochondrial oxygen consumption to restore epithelial hypoxia and reinstate colonization resistance against C. albicans (Savage et al 2023 ). Thus, 5-ASA treatment is a nonbiotic intervention that restores colonization resistance against C. albicans .…”

Mucosal Immunity to Gut Fungi in Health and Inflammatory Bowel Disease

“…biofilm and hyphal development [41]. A recent pre-print article identified that the ubiquitous UC treatment 5-aminosalicylic acid can reduce post-antibiotic C. albicans bloom, which is thought to be promoted by the restoration of mucosal hypoxia and gut re-colonisation by Clostridia [42]. Separately, Candida tropicalis levels appear to be positively correlated with several pathogenic bacteria within the guts of CD patients, and their co-existence within biofilms is associated with more filamentous growth [9].…”