WOFAPS 2025 8th World Congress of Pediatric Surgery

Yinbing Tang, Jinhu Wang

Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children’s Regional Medical Center

Objective: To investigate the characteristics of gut microbiome and fecal metabolites in neuroblastoma (NB), and explore potential probiotics and postbiotics for NB diagnosis and therapy.

Approach: The gut microbiome discriminations between NB and ganglioneuroblastoma (GNB)/ganglioneuroma (GN) from newly diagnosed and untreated patients were determined by shotgun metagenomic sequencing. Correlation between crucial species and neuron-specific enolase (NSE) level was analyzed. Metabolomic was employed and analyzed combined with metagenomic data to identify the major bioactive gut derived metabolites. Mouse model was established to explore the tumor-inhibiting role of flavonoid metabolites. Cell proliferation, apoptosis assays and signaling pathway detections were conducted to clarify the underlying mechanisms for NB differentiation and maturation.

Results: A distinctive microbiome was observed in NB with decreased abundance of species in genera Blautia, Roseburia, Bifidobacterium. The altered gut microbiome presented a good diagnostic efficiency with an AUC of 0.76. Additionally, the abundance of Blautia wexlerae, Roseburia faecis, Bifidobacterium pseudocatenulatum was negatively correlated with serum NSE concentrations. Functional pathways such as biosynthesis of amino acid and degradation of flavonoids was eriched in GNB/GN. Consistently, metabolomic data showed biosynthesis of plant secondary metabolites and degradation of flavonoids were upregulated in GNB/GN, suggesting the importance of flavonoids metabolites in suppressing NB progression. Metabolites composition was distinguishing between NB and GNB/GN. Specifically, several flavonoid metabolites especially 6,7,4'-Trihydroxyisoflavone (THIF) and Equol 7-O-Glucuronide (Eq) were significantly decreased in NB. And flavonoid metabolites were positively correlated with species in Blautia and Roseburia. Furthermore, animal model showed an impressive efficacy of THIF and Eq in suppressing tumor growth and promoting NB differentiation. Mechanistically, THIF and Eq inhibited proliferation and promoted apoptosis of NB cells via PI3K/AKT/mTOR signaling pathway.

Conclusion: Our findings highlight gut microbiota an indicative potential for NB diagnosis and provide prospective postbiotics for improving NB prognosis.