Potential Cause-and-Effect Relationship between Gut Microbiota and Childhood Neuroblastoma: A Mendelian Randomization Analysis.

Abstract

To analyze the potential causal-effect of gut microbiota (GM) on neuroblastoma (NB) risk using a Mendelian randomization (MR) study. A two-sample MR study was conducted using summary statistics of the GM from the largest available meta-analysis of genome-wide association studies conducted by the MiBioGen consortium. Pooled statistics for childhood NB were obtained from the IEU Consortium release data (1627 cases and 3254 controls). Inverse variance-weighted, weighted median, MR-Egger, and weighted mod were used to examine the causal relationship between GM and childhood NB. Single-nucleotide polymorphism (SNP) genes of positive GM were extracted using the PLINK program, and correlations between key SNP genes and tumor-regulated genes were analyzed. Functional enrichment analysis and transcription factor prediction were performed. Inverse variance weighted (IVW) results indicated that Erysipelotrichia exerted a protective effect against childhood NB (odds ratio = 0.371, 95% Confidence interval: 0.173 - 0.795, P = 0.011) and that Oscillospira exerted a risk effect against childhood NB (odds ratio = 2.378, 95% Confidence interval: 1.121 - 5.043, P = 0.024), indicating the association of GM with childhood NB. Further screening analysis using the IVW test revealed a reliable causal relationship between Erysipelotrichia and NB. Two SNP genes (MUC4 and PELI2) of Erysipelotrichia were extracted and analyzed. Both key genes were significantly associated with tumor-regulated genes, enriched in several pathways associated with tumor progression, and correlated with several upstream transcription factors. It was observed that Erysipelotrichia is causally associated with NB using a two-sample MR study. Furthermore, the discovery of two SNP genes, MUC4 and PELI2, provides potential targets for the diagnosis and treatment of NB.