THE IMPACT OF HEALTHY FECAL MATERIAL TRANSPLANTATION ON GLIOBLASTOMA

Glioblastoma (GB) is the most lethal brain tumor with a 5-year survival rate of approximately 5%. Increasing evidence indicates that patients with glioblastoma exhibit an altered gut microbiota (GM) compared to healthy individuals, highlighting the relevance of the gut–brain axis in glioma progression. Among strategies to modulate the GM composition, fecal material transplantation (FMT) is the most direct approach. FMT consists of transferring fecal material from a healthy donor to a diseased recipient, often following broad-spectrum antibiotic (ABX) pre-treatment to facilitate microbial engraftment. To investigate whether FMT influences glioma development, mice orthotopically injected with GL261 murine cells received FMT from age-matched healthy mice or vehicle (PBS) through oral gavage. Treatments were administered three times weekly for two weeks, with or without ABX pre-treatment. FMT from healthy donors significantly reduced glioma growth in both ABX-pretreated and untreated mice, compared to the PBS or ABX controls. Although GM composition was successfully modulated in all groups, only the ABX+FMT group exhibited an increased frequencies of circulating and intratumoral CD107⁺ cytotoxic NK cells. The stronger NK-cell-mediated cytotoxicity was associated with increased IL-15 trans-presentation by dendritic cells and subsequent cytokine uptake by NK-cell in vivo. Preliminary in vitro analyses suggest that NK-cell activation is specifically triggered by bacterial extracellular vesicles (BEVs), a main GM-derived, isolated from ABX+FMT mice. Overall, these findings show that ABX pre-treatment followed by FMT induces a robust anti-tumor immune response, leading to sustained inhibition of glioma growth. This approach may represent a novel adjuvant therapeutic strategy for glioblastoma patients.