AUTHOR=Yan Jia-Ying , Lin Tsung-Han , Jong Yu-Tang , Hsueh Jun-Wei , Wu Sze-Hsien , Lo Hsiu-Jung , Chen Yee-Chun , Pan Chien-Hsiung 

TITLE=Microbiota signatures associated with invasive Candida albicans infection in the gastrointestinal tract of immunodeficient mice

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=13

YEAR=2024

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1278600

DOI=10.3389/fcimb.2023.1278600

ISSN=2235-2988

ABSTRACT=<p><italic>Candida albicans</italic> is a commensal microorganism in the human gut but occasionally causes invasive <italic>C. albicans</italic> infection (ICA), especially in immunocompromised individuals. Early initiation of antifungal therapy is associated with reduced mortality of ICA, but rapid diagnosis remains a challenge. The ICA-associated changes in the gut microbiota can be used as diagnostic and therapeutic targets but have been poorly investigated. In this study, we utilized an immunodeficient Rag2γc (<italic>Rag2</italic>-/-<italic>il2γc</italic>-/-) mouse model to investigate the gut microbiota alterations caused by <italic>C. albicans</italic> throughout its cycle, from its introduction into the gastrointestinal tract to invasion, in the absence of antibiotics. We observed a significant increase in the abundance of <italic>Firmicutes</italic>, particularly <italic>Lachnospiraceae</italic> and <italic>Ruminococcaceae</italic>, as well as a significant decrease in the abundance of <italic>Candidatus Arthromitus</italic> in mice exposed to either the wild-type SC5314 strain or the filamentation-defective mutant (<italic>cph1/cph1 efg1/efg1</italic>) HLC54 strain of <italic>C. albicans</italic>. However, only the SC5314-infected mice developed ICA. A linear discriminate analysis of the temporal changes in the gut bacterial composition revealed <italic>Bacteroides vulgatus</italic> as a discriminative biomarker associated with SC5314-infected mice with ICA. Additionally, a positive correlation between the <italic>B. vulgatus</italic> abundance and fungal load was found, and the negative correlation between the <italic>Candidatus Arthromitus</italic> abundance and fungal load after exposure to <italic>C. albicans</italic> suggested that <italic>C. albicans</italic> might affect the differentiation of intestinal Th17 cells. Our findings reveal the influence of pathogenic <italic>C. albicans</italic> on the gut microbiota and identify the abundance of <italic>B. vulgatus</italic> as a microbiota signature associated with ICA in an immunodeficient mouse model.</p>