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Association of maternal gut microbial metabolites with gestational diabetes mellitus: evidence from an original case-control study, meta-analysis, and Mendelian randomization

European Journal of Clinical Nutrition (2024)Cite this article

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Abstract

Background

The associations of gut microbial metabolites, such as trimethylamine N-oxide (TMAO), its precursors, and phenylacetylglutamine (PAGln), with the risk of gestational diabetes mellitus (GDM) remain unclear.

Methods

Serum samples of 201 women with GDM and 201 matched controls were collected and then targeted metabolomics was performed to examine the metabolites of interest. Multivariable conditional logistic regression was applied to investigate the relationship between metabolites and GDM. Meta-analysis was performed to combine our results and four similar articles searched from online databases, and Mendelian randomization (MR) analysis was eventually conducted to explore the causalities.

Results

In the case-control study, after dichotomization and comparing the higher versus the lower group, the adjusted odds ratio and 95% confidence interval of choline and L-carnitine with GDM were 2.124 (1.186–3.803) and 0.293 (0.134–0.638), respectively; but neutral relationships between TMAO, betaine, and PAGln with GDM were observed. The following meta-analysis consistently revealed that L-carnitine was negatively associated with GDM. However, MR analyses showed no evidence of causalities.

Conclusions

Maternal levels of L-carnitine were related to the risk of GDM in both the original case-control study and meta-analysis. However, we did not observe any genetic evidence to establish a causal relationship between this metabolite and GDM.

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Fig. 1: The boxplot of gut microbial metabolites concentrations in GDM patients and controls.
Fig. 2: Difference of gut microbial metabolites expressions in GDM patients and controls in the meta-analysis.

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Data availability

Data are available from the corresponding author upon reasonable request.

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Acknowledgements

We want to thank the participants and investigators of the Framingham Heart Study, the TwinsUK study, the Kooperative Gesundheitsforschung in der Region Augsburg study, and the FinnGen study.

Funding

JY is currently receiving grant from the National Natural Science Fund of China (grant number: 82273635). XZ is currently receiving grant from the Gusu Health Talents Program Training Project in Suzhou (grant number: GSWS2023064).

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Authors and Affiliations

  1. Suzhou Center for Disease Prevention and Control, Suzhou, China

    Mengxin Yao & Xiaoyan Zhu

  2. Department of Epidemiology and Health Statistics, Medical College of Soochow University, Suzhou, China

    Mengxin Yao, Yue Xiao, Yaling Ding, Fei Liang, Zhuoqiao Yang, Wenxin Ge & Jieyun Yin

  3. Nanjing Municipal Center for Disease Control and Prevention, Nanjing, China

    Yanqun Sun

  4. Department of Geriatrics, Guangzhou First People’s Hospital, South China University of Technology, Guangzhou, China

    Bing Zhang

  5. Taicang Affiliated Hospital of Soochow University, The First People’s Hospital of Taicang, 58 Changsheng Road, Suzhou, China

    Qiuping Ma & Songliang Liu

  6. Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, Medical College of Soochow University, Suzhou, China

    Lili Xin & Jieyun Yin

  7. School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Xiaoyan Zhu

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Contributions

MY: Conceptualization, Software, Validation, Investigation, Writing - Original Draft. YX: Methodology, Investigation, Data Curation, Formal analysis. YS: Writing - Review & Editing. BZ: Writing - Review & Editing, Resources. YD: Investigation, Data Curation, Visualization. QM: Conceptualization, Resources, Supervision. FL: Software, Investigation, Data Curation. ZY: Investigation, Data Curation. WG: Investigation, Data Curation, Visualization. SL: Resources, Supervision. LX: Conceptualization. JY: Conceptualization, Writing - Review & Editing, Supervision, Funding acquisition. XZ: Resources, Writing - Review & Editing, Supervision, Funding acquisition.

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Correspondence to Jieyun Yin or Xiaoyan Zhu.

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This original study was approved by the ethics committee of Soochow University and First People’s Hospital of Taicang. Written informed consent was obtained from all the patients.

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Yao, M., Xiao, Y., Sun, Y. et al. Association of maternal gut microbial metabolites with gestational diabetes mellitus: evidence from an original case-control study, meta-analysis, and Mendelian randomization. Eur J Clin Nutr (2024). https://doi.org/10.1038/s41430-024-01502-z

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