Investigating causal associations among gut microbiota, gut microbiota-derived metabolites, and gestational diabetes mellitus: a bidirectional Mendelian randomization study

Abstract

Background: Previous studies have shown that gut microbiota (GM) and gut microbiota-derived metabolites are associated with gestational diabetes mellitus (GDM). However, the causal associations need to be treated with caution due to confounding factors and reverse causation. Methods: This study obtained genetic variants from genome-wide association study including GM ( N = 18,340), GM-derived metabolites ( N = 7,824), and GDM (5,687 cases and 117,89 controls). To examine the causal association, several methods were utilized, including inverse variance weighted, maximum likelihood, weighted median, MR-Egger, and MR.RAPS. Additionally, reverse Mendelian Randomization (MR) analysis and multivariable MR were conducted to confirm the causal direction and account for potential confounders, respectively. Furthermore, sensitivity analyses were performed to identify any potential heterogeneity and horizontal pleiotropy. Results: Greater abundance of Collinsella was detected to increase the risk of GDM. Our study also found suggestive associations among Coprobacter , Olsenella , Lachnoclostridium , Prevotella9 , Ruminococcus2 , Oscillibacte , and Methanobrevibacter with GDM. Besides, eight GM-derived metabolites were found to be causally associated with GDM. For the phenylalanine metabolism pathway, phenylacetic acid was found to be related to the risk of GDM. Conclusions: The study first used the MR approach to explore the causal associations among GM, GM-derived metabolites, and GDM. Our findings may contribute to the prevention and treatment strategies for GDM by targeting GM and metabolites, and offer novel insights into the underlying mechanism of the disease.

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“…Meanwhile, Dorea is associated with autism spectrum disorder (ASD) ( Li Z. et al, 2023 ), inflammatory bowel disease (IBD) ( Zhang et al, 2021 ), hypertensive disorders in pregnancy (HDP) ( Wu et al, 2023a ), polycystic ovary syndrome (PCOS) ( Min et al, 2023 ), hemorrhagic stroke ( Shen et al, 2023 ), age-related macular degeneration (AMD) ( Li and Lu, 2023 ), nicotine dependence ( Chen Y. et al, 2023 ), and insomnia ( Li Z. et al, 2023 ). Similarly, Lachnochlostrium is linked to multiple diseases, including Alzheimer’s disease (AD) ( Ning et al, 2022 ), nonalcoholic fatty liver disease (NAFLD) ( Zhang et al, 2023 ), myasthenia gravis ( Su et al, 2023 ), type 2 diabetes ( Li and Li, 2023 ), gestational diabetes mellitus ( Wu et al, 2023b ), renal cell cancer ( Yin et al, 2023 ), insomnia ( Li Z. et al, 2023 ), peripheral artery disease ( Shi et al, 2024 ), peripheral atherosclerosis ( Jiang et al, 2023 ), Primary open-angle glaucoma (POAG) ( Zhou et al, 2024 ), and intervertebral disc degeneration ( Zheng et al, 2023 ). These studies demonstrate a causal association between gut microbiota and diseases.…”

Cross-talk between the gut microbiota and hypothyroidism: a bidirectional two-sample Mendelian randomization study

“…All statistical analyses were conducted using R version 4.2.3 (R Foundation for Statistical Computing, Vienna, Austria). For the purpose of performing MR analyses, TwosampleMR (0.5.6) ( 38 ) and MR-PRESSO (1.0) ( 36 ) were employed. Figure 2 displays the MR diagram utilized in this study.…”