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Intracellular acidification by microbiota-derived valeric acid facilitates trans-kingdom ecology limiting Candida parapsilosis colonization

Year: 2026
Type: article
Abstract: In hematopoietic cell transplant (HCT) patients, intestinal Candida parapsilosis expansion and translocation can cause life-threatening candidemia, yet whether commensal intestinal bacteria prevent Candida expansion remains incompletely defined. Here, we trained a machine learning model on supernatant metabolomic profiles of Lachnospiraceae to identify bacteria-derived inhibitors of fungal growth, identifying valeric and butyric acids as top hits. Fecal samples from HCT patients supported this association, with valeric and butyric acid levels inversely correlating with C. parapsilosis growth. In cell culture and mice, valeric acid inhibited C. parapsilosis growth by increasing intracellular acidification. Administration of glycerol valerate, or free or microencapsulated valeric acid, to release valeric acid along the entire intestinal tract blunted C. parapsilosis growth at murine intestinal sites where valeric acid was detected. Thus, machine learning identified a mechanistic driver of trans-kingdom ecology limiting C. parapsilosis intestinal expansion and may inform strategies to reduce patient risk of candidiasis.
DOI: 10.1016/j.chom.2026.05.008
Authors: Keiko Yasuma-Mitobe, Chen Liao, Tibor Németh, Kevin Byrne, Audrey Billips, Ruben Jose Jesus Faustino Ramos, Cristine Nicole Salinas, Eric Chan, Martina Perissinoto, Sophia Adami-Sampson, Ayesha Salman, Ashley M. Sidebottom, George Plitas, Geraldine Butler, Justin R. Cross, Eric G. Pamer, Attila Gácser, Joao B. Xavier, Tobias M. Hohl
Institutions: Memorial Sloan Kettering Cancer Center, Dartmouth College, University of Szeged, University College Dublin, Cornell University, Rockefeller University, University of Chicago
Language: English
Open Access status: hybrid
Estimated APC paid: $10,400
Funders: Takeda Science Foundation, Geoffrey Beene Foundation, National Institutes of Health, Japan Society for the Promotion of Science, National Cancer Institute, National Institute of Allergy and Infectious Diseases
Awards: Understanding the molecular mechanisms regulating fungal colonization and disease in the mammalian intestinal niche, G3037845930, G6733382815, G7821288898, Unraveling the ecology of intestinal fungal expansion in immunocompromised patients through computational modeling and machine learning, Cancer Center Support Grant, INITIATION OF THE IMMUNE RESPONSE TO ASPERGILLUS FUMIGATUS, Unraveling the ecology of intestinal fungal expansion in immunocompromised patients through computational modeling and machine learning
OpenAlex ID: W7163528503
FWCI: 2.067
Cites: 83
Cited by: 1
Related to: 10