Exogenous chemical exposures and metabolic disruptions in hyperuricemia: a multi-omics mediation study

Hyperuricemia has emerged as a significant public health concern. However, the relationship between hyperuricemia and both individual and mixed exogenous chemicals remains poorly understood, and the underlying mechanisms are still unclear.

This study aimed to elucidate the risk factors and biological mechanisms underlying hyperuricemia by integrating multi-omics data.

UPLC-MS-based methods were employed to quantify 186 exogenous chemicals and profile metabolites from serum samples of 298 pairs of hyperuricemia patients and matched control subjects.

Significant disturbances in amino acid metabolism, energy metabolism, and gut microbiota-related metabolism were observed in hyperuricemia patients. The concentrations of perfluoroheptanoic acid, perfluorobutanesulfonate, sodium 4-chlorophenoxyacetate, and indole-3-butyric acid were significantly higher in hyperuricemia patients. A positive association was observed between combined exposures and hyperuricemia risk, with indole-3-butyric acid being the most significant contributor. Perfluorinated compounds may affect uric acid excretion via gut microbiome-related metabolites. Indole-3-butyric acid might modulate the enzymatic activity of various acyl-CoA dehydrogenases, leading to disruptions in fatty acid metabolism and an increased risk of hyperuricemia. Furthermore, genetic susceptibility appears to further increase the risk of hyperuricemia.

In summary, hyperuricemia is related to the interplay of environmental exposures and individual genetic susceptibility, with metabolic dysregulation serving as a crucial mediating link. These findings offer novel insights into the potential health risks associated with exogenous chemical exposures.