Oral administration of live- or heat-killed Candida albicans worsened cecal ligation and puncture sepsis in a murine model possibly due to an increased serum (1→3)-β-D-glucan

• Published in: PloS one 2017-07, Vol.12 (7), p.e0181439-e0181439
• Main Authors: Panpetch, Wimonrat, Somboonna, Naraporn, Bulan, Dewi Embong, Issara-Amphorn, Jiraphorn, Finkelman, Malcolm, Worasilchai, Navaporn, Chindamporn, Ariya, Palaga, Tanapat, Tumwasorn, Somying, Leelahavanichkul, Asada
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animal models; Animals; Antibiotics; Antifungal agents; Bacteria; beta-Glucans - blood; Biology and Life Sciences; Blood Bactericidal Activity; Bone marrow; Candida; Candida albicans; Candida albicans - physiology; Candidemia; Cecum; Cecum - pathology; Cytokines - blood; Disease Models, Animal; Drug dosages; E coli; Escherichia coli - metabolism; Feces - microbiology; Fluconazole; Fungi; Gastrointestinal Microbiome; Glucan; Heat; Intensive care; Intestinal microflora; Intestine; Laboratory animals; Lactobacillus rhamnosus; Ligation; Macrophages; Macrophages - metabolism; Male; Medicine; Medicine and Health Sciences; Mice; Mice, Inbred ICR; Microbiota; Oral administration; Punctures; Research and Analysis Methods; Rodents; Sepsis; Sepsis - blood; Sepsis - microbiology; Surgery; Survival Analysis; Time Factors; Tumor necrosis factor-TNF; Xenichthys xanti
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0181439

Candida albicans is the most common fungus in the human intestinal microbiota but not in mice. To make a murine sepsis model more closely resemble human sepsis and to explore the role of intestinal C. albicans, in the absence of candidemia, in bacterial sepsis, live- or heat-killed C. albicans was orally administered to mice at 3h prior to cecal ligation and puncture (CLP). A higher mortality rate of CLP was demonstrated with Candida-administration (live- or heat-killed) prior to CLP. Fecal Candida presented only in experiments with live-Candida administration. Despite the absence of candidemia, serum (1→3)-β-D-glucan (BG) was higher in CLP with Candida-administration than CLP-controls (normal saline administration) at 6h and/or 18h post-CLP. Interestingly, fluconazole attenuated the fecal Candida burden and improved survival in mice with live-Candida administration, but not CLP-control. Microbiota analysis revealed increased Bacteroides spp. and reduced Lactobacillus spp. in feces after Candida administration. Additionally, synergy in the elicitation of cytokine production from bone marrow-derived macrophages, in vitro, was demonstrated by co-exposure to heat-killed E. coli and BG. In conclusion, intestinal abundance of fungi and/or fungal-molecules was associated with increased bacterial sepsis-severity, perhaps through enhanced cytokine elicitation induced by synergistic responses to molecules from gut-derived bacteria and fungi. Conversely, reducing intestinal fungal burdens decreased serum BG and attenuated sepsis in our model.