{"doi":"10.1093/neuonc/noaf024","title":"Intestinal <i>Bacteroides</i> drives glioma progression by regulating CD8+ T cell tumor infiltration","abstract":"BACKGROUND: The intestinal microbiota regulates normal brain physiology and the pathogenesis of several neurological disorders. While prior studies suggested that this operates through immune cells, the underlying mechanisms remain unclear. Leveraging 2 well-characterized murine models of low-grade glioma occurring in the setting of the neurofibromatosis type 1 (NF1) cancer predisposition syndrome, we sought to determine the impact of the gut microbiome on optic glioma progression. METHODS: Neurofibromatosis type 1 (Nf1)-mutant mice genetically engineered to develop optic pathway gliomas (Nf1OPG mice) by 3 months of age were reared under germ-free (GF) conditions, treated with specific cocktails of antibiotics, or given fecal matter transplants (FMTs). Intestinal microbial species were identified by 16S genotyping. Neutralizing transforming growth factor-beta (TGFβ) antibodies were delivered systemically, while in vitro experiments used isolated murine microglia and T cells. Single-cell RNA sequencing analysis was performed using established methods. RESULTS: Nf1 OPG mice raised in a GF environment or postnatally treated with vancomycin did not harbor optic gliomas or exhibit OPG-induced retinal nerve fiber layer thinning, which was reversed following conventionally raised mouse FMT or colonization with Bacteroides species. Moreover, this intestinal microbiota-regulated gliomagenesis was mediated by circulating TGFβ, such that systemic TGFβ neutralization reduced Nf1-OPG growth. TGFβ was shown to act on tumor-associated monocytes to induce Ccl3 expression and recruit CD8+ T cells necessary for glioma growth. CONCLUSIONS: Taken together, these findings establish, for the first time, a mechanistic relationship between Bacteroides in the intestinal microbiome and NF1-LGG pathobiology, suggesting both future predictive risk assessment strategies and therapeutic opportunities.","journal":"Neuro-Oncology","year":2025,"id":515844,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9573,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1224611,"name":"Xuanhe Qi","orcid":null,"position":1,"is_corresponding":false},{"id":1224076,"name":"Rui Mu","orcid":"0009-0005-4221-4159","position":2,"is_corresponding":false},{"id":1381231,"name":"Xuanwei Li","orcid":null,"position":3,"is_corresponding":false},{"id":1381232,"name":"Talia Eligator","orcid":null,"position":4,"is_corresponding":false},{"id":1275456,"name":"Megan Ouyang","orcid":null,"position":5,"is_corresponding":false},{"id":414884,"name":"Stephanie L Bozeman","orcid":null,"position":6,"is_corresponding":false},{"id":491706,"name":"Rachel Rodgers","orcid":"0000-0001-7787-0491","position":7,"is_corresponding":false},{"id":777256,"name":"Somya Aggarwal","orcid":"0000-0002-4586-9485","position":8,"is_corresponding":false},{"id":302322,"name":"Danielle E. Campbell","orcid":"0000-0002-4072-3874","position":9,"is_corresponding":false},{"id":716507,"name":"Lawrence A. Schriefer","orcid":"0000-0001-6865-8683","position":10,"is_corresponding":false},{"id":298001,"name":"Megan T. Baldridge","orcid":"0000-0002-7030-6131","position":11,"is_corresponding":false},{"id":295596,"name":"David H. Gutmann","orcid":"0000-0002-3127-5045","position":12,"is_corresponding":false},{"id":663297,"name":"Jit Chatterjee","orcid":"0000-0002-2444-9748","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-19T02:48:44.647022Z","pmid":"39868555","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}