Relationship Between Gut Microbiota and Phenylalanine Levels: A Mendelian Randomization Study

The specific members of the gut microbiota linked to phenylketonuria remain to be identified. This study aimed to assess the association between gut microbiota on phenylalanine (Phe) levels using a two-sample Mendelian randomization (MR) approach. Summary statistics from genome-wide association studies (GWAS) related to individual gut microbiota were obtained from the MiBioGen Global Consortium database. The data set of Phe levels was derived from GWAS summary datasets. Inverse variance weighting (IVW) served as the primary method to infer the causal relationship between gut microbiota and Phe levels. Additional pleiotropy and heterogeneity tests were conducted to evaluate the reliability of the findings. The Family XIII AD3011 group had a protective effect on Phe levels (OR = 0.962, 95% CI: 0.942-0.982, p < 0.001), and these associations remained significant after FDR correction (adjusted p-value = 0.027). There was no evidence of notable heterogeneity and horizontal pleiotropy among the instrumental variables. Our data indicate that Family XIII AD3011 group is associated with reduced Phe levels, highlighting a potential link between gut microbiota and Phe levels. Although MR analysis supports a causal relationship, it may not precisely estimate the effect size, necessitating further studies to validate these findings and quantify the association.