title: Using Bayesian modelling to investigate factors governing antibiotic-induced Candida albicans colonization of the GI tract.
abstract: Receipt of broad-spectrum antibiotics enhances Candida albicans colonization of the GI tract, a risk factor for haematogenously-disseminated candidiasis. To understand how antibiotics influence C. albicans colonization, we treated mice orally with vancomycin or a combination of penicillin, streptomycin, and gentamicin (PSG) and then inoculated them with C. albicans by gavage. Only PSG treatment resulted in sustained, high-level GI colonization with C. albicans. Furthermore, PSG reduced bacterial diversity in the colon much more than vancomycin. Both antibiotic regimens significantly reduced IL-17A, IL-21, IL-22 and IFN-γ mRNA levels in the terminal ileum but had limited effect on the GI fungal microbiome. Through a series of models that employed Bayesian model averaging, we investigated the associations between antibiotic treatment, GI microbiota, and host immune response and their collective impact on C. albicans colonization. Our analysis revealed that bacterial genera were typically associated with either C. albicans colonization or altered cytokine expression but not with both. The only exception was Veillonella, which was associated with both increased C. albicans colonization and reduced IL-21 expression. Overall, antibiotic-induced changes in the bacterial microbiome were much more consistent determinants of C. albicans colonization than either the GI fungal microbiota or the GI immune response.
authors: J. Craig Venter Institute, Rockville, MD, USA.
authors: Jyoti
authors: J
authors: Shankar
authors: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
authors: Norma V
authors: NV
authors: Solis
authors: J. Craig Venter Institute, Rockville, MD, USA.
authors: Stephanie
authors: S
authors: Mounaud
authors: J. Craig Venter Institute, Rockville, MD, USA.
authors: Sebastian
authors: S
authors: Szpakowski
authors: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
authors: Hong
authors: H
authors: Liu
authors: J. Craig Venter Institute, Rockville, MD, USA.
authors: Liliana
authors: L
authors: Losada
authors: J. Craig Venter Institute, Rockville, MD, USA.
authors: William C
authors: WC
authors: Nierman
authors: 1] Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA [2] David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors: Scott G
authors: SG
authors: Filler
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000166:cytology / Q000187:drug effects; D001499:Bayes Theorem; D002176:Candida albicans / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D016208:Databases, Factual; D005658:Fungi / Q000166:cytology / Q000187:drug effects; D041981:Gastrointestinal Tract / Q000382:microbiology*; D007082:Ileum / Q000378:metabolism / Q000382:microbiology; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota; D012336:RNA, Ribosomal, 16S / Q000032:analysis; D000097043:Interleukin-22; D000098546:Interleukin-21
chemical_list: D000900:Anti-Bacterial Agents; D007371:Interferon-gamma; D020381:Interleukin-17; D007378:Interleukins; D012336:RNA, Ribosomal, 16S; D000097043:Interleukin-22; D000098546:Interleukin-21
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