Metabolome-wide association study of phenylalanine in plasma of common marmosets

Little systematic knowledge exists concerning the impacts of cumulative lifelong exposure, termed the exposome, on requirements for nutrients. Phenylalanine (Phe) is an essential dietary amino acid with an aromatic ring structure similar to endogenous metabolites, dietary compounds and environmental agents. Excess plasma Phe in genetic disease or nutritional deficiency of Phe has adverse health consequences. In principle, structurally similar chemicals interfering with Phe utilization could alter Phe requirement at an individual level. As a strategy to identify components of the exposome that could interfere with Phe utilization, we tested for metabolites correlating with Phe concentration in plasma of a non-human primate species, common marmosets (Callithrix jacchus). The results of tests for more than 5,000 chemical features detected by high-resolution metabolomics showed 17 positive correlations with Phe metabolites and other amino acids. Positive and negative correlations were also observed for 33 other chemicals, which included matches to endogenous metabolites and dietary, microbial and environmental chemicals in database searches. Chemical similarity analysis showed many of the matches had high structural similarity to Phe. Together, the results show that chemicals in marmoset plasma could impact Phe utilization. Such chemicals could contribute to early lifecycle developmental disorders when neurological development is vulnerable to Phe levels.