Dataset Information

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.

SUBMITTER: Wu X

PROVIDER: S-EPMC10497006 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

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

Wu Xinrui X Lin Dihui D Li Qi Q Cai Jiawang J Huang Houxiang H Xiang Tianyu T Tan Hongzhuan H

Aging 20230823 16

<h4>Background</h4>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.<h4>Methods</h4>This study obtained genetic variants from genome-wide association study including GM (<i>N</i> = 18,340), GM-derived metabolites (<i>N</i> = 7,824), and GDM (5,687 cases and 117,89 controls). To examine ...[more]

PMID: 37616057

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Project description:BackgroundThe interaction between the intestinal flora and gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) remains poorly understood, despite the known effect of the gut microbiota on gastrointestinal adenocarcinomas. Hence, the present research aimed to determine the potential causal correlation between the intestinal flora and GEP-NENs by conducting a bidirectional Mendelian randomization (MR) analysis.MethodsTwo-sample MR analysis was conducted using the summary statistics of the gut microbiota from the MiBioGen consortium and those of GEP-NENs from the FinnGen research project. The inverse-variance weighted approach was utilized as the primary analytical method. To enhance the robustness of our findings, multiple sensitivity tests were performed, including Cochran's Q test for evaluating heterogeneity, the MR-Egger intercept test to detect horizontal pleiotropy, and the MR-PRESSO test to identify outliers and assess pleiotropy bias. Additionally, a leave-one-out analysis was performed to validate the consistency of our findings. The MR-Steiger test was also utilized to determine the causal direction in the correlation between the gut microbiota and GEP-NENs. Finally, a reverse MR analysis was performed to assess reverse causality between the intestinal flora and GEP-NENs.ResultsWe identified 42 taxa of the gut microbiota that were potentially causally associated with GEP-NENs; of these taxa, 7, 8, 11, and 16 taxa were causally associated with pancreatic NENs, colorectal NENs, small intestinal NENs, and gastric NENs, respectively. After adjusting for false discovery rate (FDR) correction, we found significant causal links of Euryarchaeota with small intestinal NENs and Family XIII UCG-001 with gastric NENs. The sensitivity analyses confirmed the stability of these correlations. In the reverse MR analysis, colorectal NENs and small intestinal NENs were found to be associated with variations in 8 and 6 different taxa of the gut microbiota, respectively. After adjusting for FDR correction, no significant causal links were detected between GEP-NENs and the intestinal flora.ConclusionThe present study reveals a potential causal association between certain taxa of the intestinal flora and GEP-NENs, thus providing new perspectives regarding the role of the intestinal flora in the development of these tumors. These insights could provide innovative approaches to screen and prevent these diseases.

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Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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