BIOM-03. Gut microbiome α-diversity is associated with overall survival in pediatric embryonal tumors and high-grade gliomas

Introduction The gut microbiome exerts a multifaceted influence on treatment outcomes across various cancers. However, its potential role in pediatric brain tumors remains largely unexplored. Here, we report our findings delineating the gut microbiome composition and its association with survival outcomes in pediatric brain tumors. Methods Within the MIMIC program, we prospectively and longitudinally collect fecal samples from pediatric brain tumor patients (<21 years of age) at diagnosis. In this study, we analyzed the microbiome of 32 patients using 16S rRNA amplicon sequencing of the V3-V4 region. We analyzed microbial community shifts over five timepoints (117 samples) using α- and β-diversity metrics, and compared tumor groups with α-/β-diversity and ANCOMBC differential abundance analyses (DA). Lastly, the impact of baseline α-diversity on overall survival (OS) was analyzed. Results The included brain tumor patients (20 embryonal and 12 high-grade gliomas (HGGs)) did not differ in age and sex (both p = 0.7). Alpha-diversity and β-diversity for the complete population remained stable across the different timepoints. The microbiome of embryonal tumors versus HGG at baseline revealed a comparable α-diversity (Shannon-index p = 0.2). However, we observed a borderline significant difference for β-diversity (Permanova test p = 0.05). DA revealed 4 genera with a significant log-fold change between the two tumor groups. Based on an α-diversity (Shannon-index) cutoff corresponding to one-third of the respective group’s values, participants were stratified into two categories (high- vs. low-diversity). High-diversity was associated with significantly better OS compared with low-diversity. This pattern was observed in both embryonal tumors (2-year OS: 100% vs. 64% (95%CI 34-100), log-rank p = 0.04) and HGGs (1-year OS: 71% (95%CI 45-100) vs. 50% (95%CI 19-100), log-rank p = 0.03). Conclusion This is the first study to demonstrate a consistent association between the gut microbiome and survival outcomes across different pediatric brain tumor types. Additional patient enrollment is ongoing, and more rigorous analyses are underway.