Mohamed Zaynab Sidi, Wu Qiong, Jacome Maria A, Chen Jianan, Etame Arnold B
School of Medicine, Tulane University, New Orleans, LA 70112, USA.
Department of Neuro-Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
Int J Mol Sci. 2025 Mar 24;26(7):2935. doi: 10.3390/ijms26072935.
Glioblastoma (GBM) remains the most aggressive primary brain tumor, with poor survival outcomes and treatment limited to maximal safe surgical resection, chemotherapy with temozolomide, and radiotherapy. While immunotherapy and targeted treatments show promise, therapeutic resistance and disease progression remain major challenges. This is partly due to GBM's classification as a "cold tumor" with low mutational burden and a lack of distinct molecular targets for drug delivery that selectively spare healthy tissue. Emerging evidence highlights the gut microbiota as a key player in cancer biology, influencing both glioma development and treatment response. This review explores the intersectionality between the gut microbiome and GBM, beginning with an overview of microbiota composition and its broader implications in cancer pathophysiology. We then examine how specific microbial populations contribute to glioma oncogenesis, modulating immune responses, inflammation, and metabolic pathways that drive tumor initiation and progression. Additionally, we discuss the gut microbiome's role in glioma therapeutic resistance, including its impact on chemotherapy, radiotherapy, and immunotherapy efficacy. Given its influence on treatment outcomes, we evaluate emerging strategies to modulate gut flora, such as probiotics, dietary interventions, and microbiota-based therapeutics, to enhance therapy response in GBM patients. Finally, we address key challenges and future directions, emphasizing the need for standardized methodologies, mechanistic studies, and clinical trials to validate microbiota-targeted interventions in neuro-oncology. By integrating gut microbiome research into GBM treatment paradigms, we may unlock novel therapeutic avenues to improve patient survival and outcomes.
胶质母细胞瘤（GBM）仍然是最具侵袭性的原发性脑肿瘤，生存预后较差，治疗方法仅限于最大程度的安全手术切除、替莫唑胺化疗和放疗。虽然免疫疗法和靶向治疗显示出前景，但治疗耐药性和疾病进展仍然是主要挑战。部分原因是GBM被归类为“冷肿瘤”，其突变负担低，缺乏可选择性地保护健康组织的独特药物递送分子靶点。新出现的证据突出了肠道微生物群作为癌症生物学中的关键角色，影响着神经胶质瘤的发展和治疗反应。这篇综述探讨了肠道微生物群与GBM之间的交叉关系，首先概述微生物群的组成及其在癌症病理生理学中的更广泛影响。然后，我们研究特定的微生物群体如何促进神经胶质瘤的发生，调节免疫反应、炎症和驱动肿瘤起始与进展的代谢途径。此外，我们讨论肠道微生物群在神经胶质瘤治疗耐药性中的作用，包括其对化疗、放疗和免疫治疗疗效的影响。鉴于其对治疗结果的影响，我们评估调节肠道菌群的新兴策略，如益生菌、饮食干预和基于微生物群的治疗方法，以增强GBM患者的治疗反应。最后，我们阐述关键挑战和未来方向，强调需要标准化方法、机制研究和临床试验来验证神经肿瘤学中针对微生物群的干预措施。通过将肠道微生物群研究纳入GBM治疗模式，我们可能会开辟新的治疗途径，以改善患者的生存率和治疗结果。
