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To investigate the overall association between co-exposure to metals and phthalates (PAEs) and blood lipid indicators, as well as the role of metabolic disturbances and endogenous metabolites as mediators in this association.
A total of 74 residents from Guangzhou (n=35) and Qingyuan (n=39) were randomly selected, and their urine samples were analyzed for 15 metal elements and 9 PAE metabolites. Generalized linear models and generalized weighted quantile sum (gWQS) regression models were used to assess the association between individual pollutants, combined exposure, and blood lipid levels. Non-targeted metabolomics, meet-in-the-Middle (MITM) approach, and mediation analysis were performed to identify endogenous metabolites and metabolic pathways linking combined exposure with blood lipid changes, and to explore the mediating effects of metabolites.
The concentrations of seven metals, including arsenic and cadmium, and four PAE metabolites, including mono-isobutyl phthalate (MiBP), were significantly positively correlated with increased total cholesterol (TC). The weighted quantile sum (WQS) index, which represented the overall load of metal and PAE combined exposure, showed a dose-dependent relationship with TC increase. For each one-unit increase in the WQS index, TC increased by 0.43 (95% CI: 0.05-0.82) mmol/L. Eight metabolites, including perilla acid, dehydroepiandrosterone, octanoylcarnitine, arachidonic acid, estrone, kynurenine, glucose-6-phosphate, and ferulic acid, were significantly associated with the WQS index and TC levels, and exhibited significant mediating effects, and the corresponding mediation effects were 0.09 (95% CI: 0.02-0.27)，0.18 (95% CI: 0.04-0.35)、0.21 (95% CI: 0.02-0.44)、0.12 (95% CI: 0.02-0.24)、0.08 (95% CI: 0.02-0.21)、0.08 (95% CI: 0.01-0.20) and 0.09 (95% CI: 0.01-0.19), respectively. The biosynthesis pathway of steroid hormones was significantly enriched.
The biosynthesis pathway of steroid hormones and metabolites such as dehydroepiandrosterone and androstenone may mediate the overall association between combined exposure to metals and PAEs and the increase in TC levels, providing the metabolic perspective for the overall effect on blood lipids of co-exposure to metals and PAEs.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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