Intratumoral microbiota stratifies glioma malignancy and patient survival through metabolic associations
- 1Department of Cancer Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Immunotherapy, Chongqing, China
- 2Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore, Singapore
- 3Integrative Sciences and Engineering Programme, National University of Singapore Graduate School, National University of Singapore, Singapore, Singapore
Abstract
BackgroundGlioma is the most common primary malignant tumor of the central nervous system, and its clinical outcomes remain highly heterogeneous despite advances in molecular classification and therapeutic strategies. Emerging evidence suggests that the intratumoral microbiome may influence tumor progression and the tumor microenvironment; however, its role in glioma malignancy stratification and prognosis remains poorly understood. This study aimed to characterize the intratumoral microbiota of glioma tissues and investigate its associations with tumor grade, overall survival, and potential metabolic regulatory mechanisms.MethodsA total of 107 treatment-naïve glioma patients were retrospectively enrolled, and tumor tissue samples were subjected to 16S rRNA gene sequencing to profile intratumoral microbial communities. Microbial sequence processing and taxonomic annotation were performed using QIIME2 and DADA2 pipelines. Microbial diversity and compositional differences were evaluated using alpha diversity analysis, Bray–Curtis distance-based principal coordinate analysis (PCoA), and differential abundance analysis. Kaplan–Meier survival analysis, univariate Cox regression, random forest feature selection, and multivariate prognostic modeling were performed to identify microbiome-associated survival indicators. Bootstrap optimism correction was performed with 1,000 resamples. PICRUSt2 was used to predict microbial functional profiles.ResultsWe found that intratumoral microbiota composition was significantly associated with WHO grade and overall survival. Positively associated taxa, including Firmicutes and Clostridia, were enriched in low-grade gliomas and favorable-prognosis groups, whereas negatively associated taxa such as Enterobacterales and Porphyromonas gingivalis predominated in high-grade gliomas and poor-survival patients. The model based on WHO grade–associated microbiota achieved optimism-corrected AUCs of 0.71, 0.86, and 0.88 at 1, 2, and 3 years, respectively. Functional prediction suggested differences in microbial pathways related to nucleotide biosynthesis and amino acid metabolism between groups.ConclusionsCollectively, these findings suggest associations of intratumoral microbial signatures with glioma malignancy and prognosis, alongside differences in predicted microbial functional profiles. These exploratory observations warrant independent validation to clarify their biological and potential clinical relevance.
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BibTeX
@article{yao2026intratumoral,
title = {{Intratumoral microbiota stratifies glioma malignancy and patient survival through metabolic associations}},
author = {Yao Yao and Yuyan Yang and Jiaqin Song and Li Wu and Mingyue Xu and Haiyao Liu and Yih-Cherng Liou and Yih-Cherng Liou and Lei Xia and Lei Xia},
journal = {Frontiers in Cellular and Infection Microbiology},
year = {2026},
month = oct,
doi = {10.3389/fcimb.2026.1940097},
url = {https://doi.org/10.3389/fcimb.2026.1940097},
note = {CC BY},
}
RIS
TY - JOUR
TI - Intratumoral microbiota stratifies glioma malignancy and patient survival through metabolic associations
AU - Yao Yao
AU - Yuyan Yang
AU - Jiaqin Song
AU - Li Wu
AU - Mingyue Xu
AU - Haiyao Liu
AU - Yih-Cherng Liou
AU - Yih-Cherng Liou
AU - Lei Xia
AU - Lei Xia
PY - 2026
DA - 2026/10/23
JO - Frontiers in Cellular and Infection Microbiology
DO - 10.3389/fcimb.2026.1940097
UR - https://doi.org/10.3389/fcimb.2026.1940097
AB - BackgroundGlioma is the most common primary malignant tumor of the central nervous system, and its clinical outcomes remain highly heterogeneous despite advances in molecular classification and therapeutic strategies. Emerging evidence suggests that the intratumoral microbiome may influence tumor progression and the tumor microenvironment; however, its role in glioma malignancy stratification and prognosis remains poorly understood. This study aimed to characterize the intratumoral microbiota of glioma tissues and investigate its associations with tumor grade, overall survival, and potential metabolic regulatory mechanisms.MethodsA total of 107 treatment-naïve glioma patients were retrospectively enrolled, and tumor tissue samples were subjected to 16S rRNA gene sequencing to profile intratumoral microbial communities. Microbial sequence processing and taxonomic annotation were performed using QIIME2 and DADA2 pipelines. Microbial diversity and compositional differences were evaluated using alpha diversity analysis, Bray–Curtis distance-based principal coordinate analysis (PCoA), and differential abundance analysis. Kaplan–Meier survival analysis, univariate Cox regression, random forest feature selection, and multivariate prognostic modeling were performed to identify microbiome-associated survival indicators. Bootstrap optimism correction was performed with 1,000 resamples. PICRUSt2 was used to predict microbial functional profiles.ResultsWe found that intratumoral microbiota composition was significantly associated with WHO grade and overall survival. Positively associated taxa, including Firmicutes and Clostridia, were enriched in low-grade gliomas and favorable-prognosis groups, whereas negatively associated taxa such as Enterobacterales and Porphyromonas gingivalis predominated in high-grade gliomas and poor-survival patients. The model based on WHO grade–associated microbiota achieved optimism-corrected AUCs of 0.71, 0.86, and 0.88 at 1, 2, and 3 years, respectively. Functional prediction suggested differences in microbial pathways related to nucleotide biosynthesis and amino acid metabolism between groups.ConclusionsCollectively, these findings suggest associations of intratumoral microbial signatures with glioma malignancy and prognosis, alongside differences in predicted microbial functional profiles. These exploratory observations warrant independent validation to clarify their biological and potential clinical relevance.
SN - 2235-2988
ER -