{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T01:15:06Z","timestamp":1768526106070,"version":"3.49.0"},"posted":{"date-parts":[[2025,9,8]]},"group-title":"Microbiology","reference-count":102,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"National Institute of Health","award":["K24 AI12316"],"award-info":[{"award-number":["K24 AI12316"]}]},{"name":"National Institute of Health","award":["P01 AI179406"],"award-info":[{"award-number":["P01 AI179406"]}]},{"name":"National Institute of Health","award":["R01 DK070855"],"award-info":[{"award-number":["R01 DK070855"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,9,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The gut microbiota plays a critical role in constraining\n                  <jats:italic>Candida albicans<\/jats:italic>\n                  (\n                  <jats:italic>Ca<\/jats:italic>\n                  ) colonization of the gastrointestinal (GI) tract, a key precursor to disseminated fungal infection in immunocompromised hosts. Depletion of commensal microbiota increases\n                  <jats:italic>Ca<\/jats:italic>\n                  burden and promotes dissemination, yet the mechanisms of microbiota-mediated\n                  <jats:italic>Ca<\/jats:italic>\n                  colonization resistance remain poorly defined. Here, we show that gut microbiota-derived short-chain fatty acids (SCFAs) directly inhibit\n                  <jats:italic>Ca<\/jats:italic>\n                  growth by impairing hexose uptake, disrupting central carbon metabolism, and inducing intracellular acidification.\n                  <jats:italic>In vivo<\/jats:italic>\n                  , SCFAs enhance\n                  <jats:italic>Ca<\/jats:italic>\n                  colonization resistance only in the presence of an intact gut microbiome, which is required to drive SCFA-induced taxonomic shifts that further augment resistance. Commensal microbiota lacking SCFA production exhibit diminished capacity to restrict\n                  <jats:italic>Ca<\/jats:italic>\n                  colonization, while prebiotic therapy that increases luminal SCFA levels enhances\n                  <jats:italic>Ca<\/jats:italic>\n                  clearance. These findings define a critical microbiota\u2013metabolite mechanism underlying\n                  <jats:italic>Ca<\/jats:italic>\n                  colonization resistance and suggest strategies to modulate GI fungal burden and prevent invasive disease.\n                <\/jats:p>","DOI":"10.1101\/2025.09.08.674977","type":"posted-content","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T04:20:31Z","timestamp":1757391631000},"source":"Crossref","is-referenced-by-count":0,"title":["Microbiota-derived short-chain fatty acids mediate\n                  <i>Candida albicans<\/i>\n                  gastrointestinal colonization resistance"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9479-6251","authenticated-orcid":false,"given":"Animesh A.","family":"Mishra","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura 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