Abstract 709: Gut microbiome, physical activity and cognitive dysfunction among childhood brain tumor survivors

Abstract Background: Childhood brain tumor survivors (BTS) experience a significant increase in cognitive dysfunction, adversely affecting educational attainment and quality of life. The biological mechanisms of cognitive dysfunction, particularly the gut microbiome (GM) and its function, are rarely studied in childhood BTS. Physical activity (PA) may mitigate cognitive dysfunction by reducing proinflammatory GM. Associations of GM with PA and cognitive dysfunction are unknown in childhood BTS. This study investigated associations of GM with PA and cognitive dysfunction in this population. Methods: A prospective, observational study was conducted in 28 childhood BTS (60% female, 63% white, mean age 13.7 years) enrolled from Children’s Healthcare of Atlanta. 16S rRNA V3V4 gene of fecal specimens was sequenced for GM. PA and cognitive function were self-reported by the Patient-Reported Outcomes Measurement Information System-PA and Cognitive Function scales; cognitive performance (working memory [WM] and processing speed [PS]) was tested by Wechsler Adult Intelligence Scale-IV (18-21 year) or Wechsler Intelligence Scales for Children-V (7-17 year). Chi-square test analyzed the relationship of PA with cognition; Mann-Whitney and PERMANOVA tests were used for diversity analysis, and general linear models for abundance analysis. Function of 16S bacterial communities were analyzed by Tax4fun2. Results: Most survivors were diagnosed with medulloblastoma (71%) with surgery (98%) and radiotherapy (65%). 61% and 71% of survivors reported low PA and cognitive function (T-score<50); 31% reported low WM and 77% reported low PS. A higher PA indicated better self-report cognitive function (p=0.035). Survivors with normal PA and self-report cognitive function (T-score≥50) showed higher diversity than those with low PA (p=0.086), mild (p=0.026) and moderate (p=0.028) self-report cognitive dysfunction, respectively. Children with normal PA had lower abundance of proinflammatory genera UBA1819 (p=0.016), Ruminococcus gnavus group (p=0.016), Incertae sedis (p=0.026), Alistipes (p=0.026), but higher anti-inflammatory Marvinbryantia (p=0.005). Children with high normal self-report cognitive function had higher Marvinbryantia (p=0.007). Survivors with normal WM had lower Ruminococcus gnavus group (p=0.085) but higher Ruminococcus gnavus group (p=0.086) for normal PS. Fatty acid biosynthesis and vitamin metabolism were associated with PA, while glycan, lipid, and amino acid metabolisms were associated with cognitive dysfunction. Conclusions: Low PA was associated with lower diversity and more proinflammatory taxa, which are linked with cognitive dysfunction. Promoting PA and anti-inflammatory GM may be useful strategies to improve cognitive function in childhood BTS. Future work is needed to study whether GM mediates the relationship of PA with cognitive dysfunction in a large cohort. Citation Format: Jinbing Bai, Anna Janss, Claire Mazewski, Hye In Noh, Maria C. Swartz, Lisa Ingerski, Grace Fong. Gut microbiome, physical activity and cognitive dysfunction among childhood brain tumor survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 709.