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

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, , , and were significantly enriched in HGG-FMT mice, while and increased in HC-FMT mice. Furthermore, showed a positive correlation with sphingosine, sphingosine 1-phosphate, and D-sphingosine in HGG-FMT mice. Conversely, 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.