Intestinal Bacteroides drives glioma progression by regulating CD8+ T cell tumor infiltration

Changes in the gut microbiome can have profound effects on the nervous system through modulation of T cell and microglia function. Since our prior studies demonstrated that T cells and microglia positively regulate low-grade glioma growth through the establishment of T cell-microglia immune circuit, we sought to explore the impact of changes in the gut microbiota on tumor biology. For these studies, genetically engineered Neurofibromatosis type 1 (NF1) optic glioma (Nf1-OPG) mice were raised in a germ-free environment or treated with antibiotics to deplete gut bacteria. First, we demonstrated that Nf1-OPG mice raised in a germ-free (gnotobiotic) environment or treated with specific antibiotics lacked optic gliomas and had improved OPG-induced retinal pathology (increased retinal nerve fiber layer thickness). Second antibiotic-treated Nf1-OPG mice gavaged with fecal microbiota from Nf1-OPG mice raised in a standard barrier facility restored optic glioma growth. Third, we showed that both germ-free and antibiotic-treated Nf1-OPG mice exhibited reduced intra-tumoral CD8+ T cell content resulting from decreased microglia chemokine production. Collectively, these findings establish a mechanistic relationship between the gut microbiota and brain tumor growth relevant to potential therapeutic interventions for pediatric low-grade gliomas. Overall design: All experiments were performed under active Animal Studies Committee protocols at Washington University School of Medicine(Washington University in St Louis Institutional Animal Care and Use Committee).Mice?harboring?a neomycin cassette insertion in exon 31 (Nf1+/-)?with?GFAP-Cre-mediated.?Nf1?loss in neuroglial progenitors (Nf1flox/neo; GFAP-Cre, Nf1-OPG mice) (Bajenaru et al., 2003). Mice were either treated with Vancomycin or PBS from 6-12 weeks of age and optic nerves were harvested for single cell seq.