Machine learning-based association between mixed metal exposure in early pregnancy and gestational diabetes mellitus: Mediating role of bile acid metabolism

Jiemei Li; Baoying Feng; Qiufen Wei; Hongling Zhang; Chuanqiao Tang; Ning Qin; Li Wu; Qian Liao; Yucheng Huang; Yuanyuan Li; Xiaoqiang Qiu; Yang Peng; Han Li

doi:10.1016/j.ecoenv.2025.119294

Machine learning-based association between mixed metal exposure in early pregnancy and gestational diabetes mellitus: Mediating role of bile acid metabolism

Jiemei Li (Co-first Author)
, Baoying Feng (Co-first Author)
, Qiufen Wei
, Hongling Zhang
, Chuanqiao Tang
, Ning Qin
, Li Wu
, Qian Liao
, Yucheng Huang
, Yuanyuan Li
, Xiaoqiang Qiu^*
, Yang Peng^*
, Han Li^*

^*Corresponding author for this work

Department of Electrical Engineering

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

3 Downloads (CityUHK Scholars)

Abstract

Background: Gestational diabetes mellitus (GDM) is common complication in pregnancy. Most studies on the relationship between metal and GDM have centered on a single metal or a few metals mixed, and it remains unclear whether bile acids are associated with this relationship.
Objective: To investigate the association between exposure to multiple metals in early pregnancy and GDM risk, and the mediating role of serum bile acids.
Methods: Based on a Guangxi Zhuang Birth Cohort, 650 pregnant women recruited were included in the study. Multiple machine models were used to explore the key metal variables and estimate the effects of mixed metal exposure. Then, a nested case-control study was designed with 1:1 individual matching by maternal age and gestational age (n = 304). Mediation analysis was used to assess the mediating role of serum bile acids between metal exposure and GDM.
Results: Mo and Sb were found to be negatively associated with GDM risk, while Cd was positively associated with GDM risk. The BKMR model showed that mixed exposure to Mo, Cd and Sb were negatively correlated with GDM risk. Besides, multiple bile acids (such as glycocholic acid (GCA), taurochenodeoxycholic acid (TCDCA), taurocholic acid (TCA)) and nine bile acid ratios were correlated with GDM risk. Mo, Cd and Sb were significantly correlated with bile acid levels. The TCA/CA and TCDCA/CDCA played a mediating role in Sb exposure and GDM risk.
Conclusions: Our findings indicate that exposure to Mo, Cd and Sb is significantly associated with the risk of GDM, and bile acids may play a mediating role in this.
© 2025 The Author(s).

Original language	English
Article number	119294
Number of pages	12
Journal	Ecotoxicology and Environmental Safety
Volume	306
Online published	27 Oct 2025
DOIs	https://doi.org/10.1016/j.ecoenv.2025.119294
Publication status	Published - 1 Nov 2025

Funding

We thank all the participants in the study. This work was funded by the National Key Research and Development Program of China (2022YFE0132900), the National Natural Science Foundation of China (No. U22A20407, No. 21906032, No. U23A20493 and No.42167061), the Guangxi Science Fund for Distinguished Young Scholars (2024GXNSFFA010012), the Advanced Innovation Teams and Xinghu Scholars Program of Guangxi Medical University, the Guangxi Key Laboratory of Reproductive Health and Birth Defect Prevention Open Subjects (No. GXWCH-ZDKF-2022–08).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Keywords

Gestational diabetes mellitus
Metals
Bile acids
Mediation effect
Birth cohort

Publisher's Copyright Statement

This full text is made available under CC-BY-NC 4.0. https://creativecommons.org/licenses/by-nc/4.0/

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10.1016/j.ecoenv.2025.119294

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Li, J., Feng, B., Wei, Q., Zhang, H., Tang, C., Qin, N., Wu, L., Liao, Q., Huang, Y., Li, Y., Qiu, X., Peng, Y., & Li, H. (2025). Machine learning-based association between mixed metal exposure in early pregnancy and gestational diabetes mellitus: Mediating role of bile acid metabolism. Ecotoxicology and Environmental Safety, 306, Article 119294. https://doi.org/10.1016/j.ecoenv.2025.119294

@article{01ce575669f74622b2dcfb5433482530,

title = "Machine learning-based association between mixed metal exposure in early pregnancy and gestational diabetes mellitus: Mediating role of bile acid metabolism",

abstract = "Background: Gestational diabetes mellitus (GDM) is common complication in pregnancy. Most studies on the relationship between metal and GDM have centered on a single metal or a few metals mixed, and it remains unclear whether bile acids are associated with this relationship. Objective: To investigate the association between exposure to multiple metals in early pregnancy and GDM risk, and the mediating role of serum bile acids. Methods: Based on a Guangxi Zhuang Birth Cohort, 650 pregnant women recruited were included in the study. Multiple machine models were used to explore the key metal variables and estimate the effects of mixed metal exposure. Then, a nested case-control study was designed with 1:1 individual matching by maternal age and gestational age (n = 304). Mediation analysis was used to assess the mediating role of serum bile acids between metal exposure and GDM. Results: Mo and Sb were found to be negatively associated with GDM risk, while Cd was positively associated with GDM risk. The BKMR model showed that mixed exposure to Mo, Cd and Sb were negatively correlated with GDM risk. Besides, multiple bile acids (such as glycocholic acid (GCA), taurochenodeoxycholic acid (TCDCA), taurocholic acid (TCA)) and nine bile acid ratios were correlated with GDM risk. Mo, Cd and Sb were significantly correlated with bile acid levels. The TCA/CA and TCDCA/CDCA played a mediating role in Sb exposure and GDM risk. Conclusions: Our findings indicate that exposure to Mo, Cd and Sb is significantly associated with the risk of GDM, and bile acids may play a mediating role in this. {\textcopyright} 2025 The Author(s).",

keywords = "Gestational diabetes mellitus, Metals, Bile acids, Mediation effect, Birth cohort",

author = "Jiemei Li and Baoying Feng and Qiufen Wei and Hongling Zhang and Chuanqiao Tang and Ning Qin and Li Wu and Qian Liao and Yucheng Huang and Yuanyuan Li and Xiaoqiang Qiu and Yang Peng and Han Li",

year = "2025",

month = nov,

day = "1",

doi = "10.1016/j.ecoenv.2025.119294",

language = "English",

volume = "306",

journal = "Ecotoxicology and Environmental Safety",

issn = "0147-6513",

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}

Li, J, Feng, B, Wei, Q, Zhang, H, Tang, C, Qin, N, Wu, L, Liao, Q, Huang, Y, Li, Y, Qiu, X, Peng, Y & Li, H 2025, 'Machine learning-based association between mixed metal exposure in early pregnancy and gestational diabetes mellitus: Mediating role of bile acid metabolism', Ecotoxicology and Environmental Safety, vol. 306, 119294. https://doi.org/10.1016/j.ecoenv.2025.119294

Machine learning-based association between mixed metal exposure in early pregnancy and gestational diabetes mellitus: Mediating role of bile acid metabolism. / Li, Jiemei (Co-first Author); Feng, Baoying (Co-first Author); Wei, Qiufen et al.
In: Ecotoxicology and Environmental Safety, Vol. 306, 119294, 01.11.2025.

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

TY - JOUR

T1 - Machine learning-based association between mixed metal exposure in early pregnancy and gestational diabetes mellitus

T2 - Mediating role of bile acid metabolism

AU - Li, Jiemei

AU - Feng, Baoying

AU - Wei, Qiufen

AU - Zhang, Hongling

AU - Tang, Chuanqiao

AU - Qin, Ning

AU - Wu, Li

AU - Liao, Qian

AU - Huang, Yucheng

AU - Li, Yuanyuan

AU - Qiu, Xiaoqiang

AU - Peng, Yang

AU - Li, Han

PY - 2025/11/1

Y1 - 2025/11/1

N2 - Background: Gestational diabetes mellitus (GDM) is common complication in pregnancy. Most studies on the relationship between metal and GDM have centered on a single metal or a few metals mixed, and it remains unclear whether bile acids are associated with this relationship. Objective: To investigate the association between exposure to multiple metals in early pregnancy and GDM risk, and the mediating role of serum bile acids. Methods: Based on a Guangxi Zhuang Birth Cohort, 650 pregnant women recruited were included in the study. Multiple machine models were used to explore the key metal variables and estimate the effects of mixed metal exposure. Then, a nested case-control study was designed with 1:1 individual matching by maternal age and gestational age (n = 304). Mediation analysis was used to assess the mediating role of serum bile acids between metal exposure and GDM. Results: Mo and Sb were found to be negatively associated with GDM risk, while Cd was positively associated with GDM risk. The BKMR model showed that mixed exposure to Mo, Cd and Sb were negatively correlated with GDM risk. Besides, multiple bile acids (such as glycocholic acid (GCA), taurochenodeoxycholic acid (TCDCA), taurocholic acid (TCA)) and nine bile acid ratios were correlated with GDM risk. Mo, Cd and Sb were significantly correlated with bile acid levels. The TCA/CA and TCDCA/CDCA played a mediating role in Sb exposure and GDM risk. Conclusions: Our findings indicate that exposure to Mo, Cd and Sb is significantly associated with the risk of GDM, and bile acids may play a mediating role in this. © 2025 The Author(s).

AB - Background: Gestational diabetes mellitus (GDM) is common complication in pregnancy. Most studies on the relationship between metal and GDM have centered on a single metal or a few metals mixed, and it remains unclear whether bile acids are associated with this relationship. Objective: To investigate the association between exposure to multiple metals in early pregnancy and GDM risk, and the mediating role of serum bile acids. Methods: Based on a Guangxi Zhuang Birth Cohort, 650 pregnant women recruited were included in the study. Multiple machine models were used to explore the key metal variables and estimate the effects of mixed metal exposure. Then, a nested case-control study was designed with 1:1 individual matching by maternal age and gestational age (n = 304). Mediation analysis was used to assess the mediating role of serum bile acids between metal exposure and GDM. Results: Mo and Sb were found to be negatively associated with GDM risk, while Cd was positively associated with GDM risk. The BKMR model showed that mixed exposure to Mo, Cd and Sb were negatively correlated with GDM risk. Besides, multiple bile acids (such as glycocholic acid (GCA), taurochenodeoxycholic acid (TCDCA), taurocholic acid (TCA)) and nine bile acid ratios were correlated with GDM risk. Mo, Cd and Sb were significantly correlated with bile acid levels. The TCA/CA and TCDCA/CDCA played a mediating role in Sb exposure and GDM risk. Conclusions: Our findings indicate that exposure to Mo, Cd and Sb is significantly associated with the risk of GDM, and bile acids may play a mediating role in this. © 2025 The Author(s).

KW - Gestational diabetes mellitus

KW - Metals

KW - Bile acids

KW - Mediation effect

KW - Birth cohort

UR - https://www.webofscience.com/wos/woscc/full-record/WOS:001614967200008

U2 - 10.1016/j.ecoenv.2025.119294

DO - 10.1016/j.ecoenv.2025.119294

M3 - RGC 21 - Publication in refereed journal

SN - 0147-6513

VL - 306

JO - Ecotoxicology and Environmental Safety

JF - Ecotoxicology and Environmental Safety

M1 - 119294

ER -

Machine learning-based association between mixed metal exposure in early pregnancy and gestational diabetes mellitus: Mediating role of bile acid metabolism

Abstract

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UN SDGs

Research Keywords

Publisher's Copyright Statement

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