National Institute of Infectious Disease and Vaccinology, National Health Research Institutes, Miaoli, Taiwan.
School of Dentistry, China Medical University, Taichung, Taiwan.
Front Cell Infect Microbiol. 2024 Jan 17;13:1278600. doi: 10.3389/fcimb.2023.1278600. eCollection 2023.
is a commensal microorganism in the human gut but occasionally causes invasive 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 (-/--/-) mouse model to investigate the gut microbiota alterations caused by 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 , particularly and , as well as a significant decrease in the abundance of in mice exposed to either the wild-type SC5314 strain or the filamentation-defective mutant () HLC54 strain of . However, only the SC5314-infected mice developed ICA. A linear discriminate analysis of the temporal changes in the gut bacterial composition revealed as a discriminative biomarker associated with SC5314-infected mice with ICA. Additionally, a positive correlation between the abundance and fungal load was found, and the negative correlation between the abundance and fungal load after exposure to suggested that might affect the differentiation of intestinal Th17 cells. Our findings reveal the influence of pathogenic on the gut microbiota and identify the abundance of as a microbiota signature associated with ICA in an immunodeficient mouse model.
是人体肠道中的共生微生物,但偶尔会引起侵袭性感染(ICA),特别是在免疫功能低下的个体中。早期开始抗真菌治疗与降低 ICA 的死亡率相关,但快速诊断仍然是一个挑战。ICA 相关的肠道微生物群变化可用作诊断和治疗靶点,但研究甚少。在这项研究中,我们利用免疫缺陷 Rag2γc(-/-/-)小鼠模型,在没有抗生素的情况下,研究了从肠道引入到侵袭过程中引起的肠道微生物群变化。我们观察到暴露于野生型 SC5314 菌株或丝状缺陷突变体()HLC54 菌株的小鼠中,数量显著增加,尤其是和,而数量显著减少。然而,只有 SC5314 感染的小鼠才会发展为 ICA。肠道细菌组成的时间变化的线性判别分析显示为与具有 ICA 的 SC5314 感染小鼠相关的鉴别生物标志物。此外,我们还发现数量与真菌负荷之间存在正相关,而暴露于后数量与真菌负荷之间存在负相关,这表明可能会影响肠道 Th17 细胞的分化。我们的研究结果揭示了致病性对肠道微生物群的影响,并确定了数量作为免疫缺陷小鼠模型中与 ICA 相关的微生物群特征。
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