IMMU-50. DIFFERENCES IN GUT MICROBIAL COMPOSITION BETWEEN PEDIATRIC BRAIN TUMOR PATIENTS AND HEALTHY CONTROLS – THE MIMIC PROGRAM

Abstract

Abstract INTRODUCTION The gut microbiome has been hypothesized to influence tumor initiation, immune evasion and treatment response in CNS tumor patients via the gut-brain axis, but data remains limited. To begin to address this question, we compared the gut microbial composition in a cohort of pediatric high-grade brain tumor patients with healthy controls. METHODS Within the MIMIC program, we prospectively collected fecal samples from 33 pediatric brain tumor patients at diagnosis and 26 pediatric healthy controls (HC) (< 21 years of age). Samples were analyzed using 16S rRNA amplicon sequencing of the V3-V4 region. Group differences were tested through the α- and β-diversity. Additionally, differential abundance (DA) analyses were performed. RESULTS Brain tumor patients (16 embryonal and 17 glial) significantly differed in age from HC (median 8 years vs 5 years, p< 0.001). Patient vs HC comparison revealed a comparable α-diversity (Shannon-index p=0.45), but significantly different β-diversity (Permanova test p=0.02). Corrected for age, DA revealed 18 genera with a significant log fold change. Twenty five of 33 brain tumor patients received dexamethasone during or prior to fecal sampling and 32 out of 33 patients received cefazolin, a first generation narrow-spectrum cephalosporin targeting mainly gram-positive bacteria, during surgery and before sample collection. Steroid use within brain tumor patients did not statistically affect α-diversity, β-diversity or DA. However, the impact of intravenously administered cefazolin during surgery on the gut microbiome in brain tumor patients remains unknown. CONCLUSION We report significant differences in gut microbial composition between pediatric brain tumor patients at diagnosis and healthy controls. DA revealed clinically relevant differences in Agathobacter , Fusicatenibacter , Eggerthella , and Hungatella. However, differences may be impacted by cefazolin administration. If and how gut microbial composition at diagnosis is associated with treatment efficacy and toxicity is subject to further research within the MIMIC program.