{"doi":"10.1101/2023.04.17.537218","title":"5-ASA can functionally replace Clostridia to prevent a post-antibiotic bloom of <i>Candida albicans</i> by maintaining epithelial hypoxia","abstract":"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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":399079,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.958,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":863179,"name":"Derek J. Bays","orcid":"0000-0003-0264-5569","position":1,"is_corresponding":false},{"id":1175405,"name":"Mariela A. F. Gonzalez","orcid":null,"position":2,"is_corresponding":false},{"id":1175406,"name":"Eli J. Bejarano","orcid":null,"position":3,"is_corresponding":false},{"id":630398,"name":"Henry Nguyen","orcid":"0000-0002-6737-1485","position":4,"is_corresponding":false},{"id":1014301,"name":"Hugo L. P. Masson","orcid":"0009-0000-4156-8549","position":5,"is_corresponding":false},{"id":1060496,"name":"Thaynara Parente de Carvalho","orcid":"0000-0002-7158-8249","position":6,"is_corresponding":false},{"id":728915,"name":"Renato L. Santos","orcid":"0000-0002-4830-0470","position":7,"is_corresponding":false},{"id":249633,"name":"George R. Thompson","orcid":"0000-0001-8518-5750","position":8,"is_corresponding":false},{"id":630400,"name":"Andreas J. Bäumler","orcid":"0000-0001-9152-7809","position":9,"is_corresponding":false},{"id":630397,"name":"Hannah P. Savage","orcid":"0000-0002-1057-7239","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-19T01:19:51.724387Z","pmid":"37131682","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}