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

IF 9.7 1区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Environment International Pub Date : 2025-10-01 DOI:10.1016/j.envint.2025.109832

Yang Ouyang , Lvyun Sun , Di Yu , Qi Li , Shanshan Du , Xiaolin Wang , Mengyao Wang , Guowang Xu , Weimin Ye , Xinyu Liu

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Abstract

Background

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.

Objectives

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

Methods

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.

Results

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.

Conclusions

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.

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外源性化学暴露和高尿酸血症的代谢中断：多组学中介研究

背景：高尿酸血症已成为一个重要的公共卫生问题。然而，高尿酸血症与个体和混合外源性化学物质之间的关系仍然知之甚少，潜在的机制仍然不清楚。目的综合多组学数据，探讨高尿酸血症的危险因素和生物学机制。方法采用suplc - ms -based方法，对298对高尿酸血症患者和对照组的186种外源化学物质进行定量分析。结果高尿酸血症患者的氨基酸代谢、能量代谢和肠道菌群相关代谢均出现明显紊乱。高尿酸血症患者的全氟庚酸、全氟丁磺酸、4-氯苯氧乙酸钠和吲哚-3-丁酸浓度显著升高。综合暴露与高尿酸血症风险之间存在正相关，其中吲哚-3-丁酸是最显著的贡献者。全氟化合物可能通过肠道微生物相关代谢物影响尿酸排泄。吲哚-3-丁酸可能调节各种酰基辅酶a脱氢酶的酶活性，导致脂肪酸代谢中断和高尿酸血症的风险增加。此外，遗传易感性似乎进一步增加了高尿酸血症的风险。综上所述，高尿酸血症与环境暴露和个体遗传易感性的相互作用有关，代谢失调是一个重要的中介环节。这些发现为与外源性化学品接触相关的潜在健康风险提供了新的见解

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Environment International 环境科学-环境科学

CiteScore

21.90

自引率

3.40%

发文量

734

审稿时长

2.8 months

期刊介绍： Environmental Health publishes manuscripts focusing on critical aspects of environmental and occupational medicine, including studies in toxicology and epidemiology, to illuminate the human health implications of exposure to environmental hazards. The journal adopts an open-access model and practices open peer review. It caters to scientists and practitioners across all environmental science domains, directly or indirectly impacting human health and well-being. With a commitment to enhancing the prevention of environmentally-related health risks, Environmental Health serves as a public health journal for the community and scientists engaged in matters of public health significance concerning the environment.