5-ASA can functionally replace Clostridia to prevent a post-antibiotic bloom of Candida albicans by maintaining epithelial hypoxia

Savage, H. P.; Bays, D. J.; Gonzalez, M. A. F.; Bejarano, E. J.; Nguyen, H.; Masson, H. L. P.; Carvalho, T. P.; Santos, R. L.; Thompson, G.; Bäumler, A. J.

doi:10.1101/2023.04.17.537218

bioRxiv · 10.1101/2023.04.17.537218

5-ASA can functionally replace Clostridia to prevent a post-antibiotic bloom of Candida albicans by maintaining epithelial hypoxia

Savage, H. P.·Bays, D. J.·Gonzalez, M. A. F.·Bejarano, E. J.·Nguyen, H.·Masson, H. L. P.·Carvalho, T. P.·Santos, R. L.·Thompson, G.·Bäumler, A. J.

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Abstract

Antibiotic prophylaxis sets the stage for an intestinal bloom of Candida 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 against C. albicans. Streptomycin treatment, which depletes Clostridia from the gut microbiota, disrupted colonization resistance against C. albicans and 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.

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Savage, H. P., Bays, D. J., Gonzalez, M. A. F., Bejarano, E. J., Nguyen, H., Masson, H. L. P., Carvalho, T. P., Santos, R. L., Thompson, G., Bäumler, A. J.. 2023-04-17. 5-ASA can functionally replace Clostridia to prevent a post-antibiotic bloom of Candida albicans by maintaining epithelial hypoxia. https://doi.org/10.1101/2023.04.17.537218

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