Deciphering the contributions of fecal microbiota from patients with high-grade glioma to tumor development in a humanized microbiome mouse model of glioma

利用人源化微生物组小鼠胶质瘤模型,解析高级别胶质瘤患者粪便微生物群对肿瘤发展的影响

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Abstract

BACKGROUND: Recent studies have revealed associations between gut microbiota and glioma. However, the underlying mechanisms remain poorly understood. This study primarily aims to elucidate the impact of altered gut microbiota on tumor progression in glioma-bearing mice. METHODS: Fecal samples were collected from glioma patients and healthy controls to compare the effects of human-derived gut microbiota on glioma development in mice. We also analyzed the associations between these microbiota profiles and plasma metabolites. RESULTS: Significant differences were observed in both the composition and diversity of the gut microbiota between glioma patients and healthy controls. Mice transplanted with gut microbiota from high-grade glioma patients (HGG-FMT) exhibited accelerated glioma progression compared to those transplanted with microbiota from healthy individuals (HC-FMT). Specifically, Eisenbergiella, Mailhella, and Merdimonas were significantly enriched in HGG-FMT mice, while Limosilactobacillus and Anaerospora increased in HC-FMT mice. Furthermore, Merdimonas showed a positive correlation with sphingosine, sphingosine 1-phosphate, and D-sphingosine in HGG-FMT mice. Conversely, Limosilactobacillus was positively correlated with stearidonic acid and eicosapentaenoic acid in HC-FMT mice. CONCLUSIONS: Our findings demonstrate that gut microbiota from high-grade glioma patients can promote glioma progression in mice, potentially through mechanisms involving sphingosine 1-phosphate. This metabolite may enter the bloodstream and accelerate glioma growth, offering novel insights into glioma pathogenesis and potential treatment options.

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