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Published on: July 31, 2019
Causal Relationships between Gut Microbiotas, Blood Metabolites, and Neuroendocrine Tumors: A Mediated Mendelian
ZheXu Cao1, JiangSheng Huang1, Xia Long2
1Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, China.
Introduction:
Neuroendocrine tumors (NETs) are a heterogeneous group of epithelial tumors originating from different anatomical sites, and identifying the gut microbiota and metabolic mechanisms involved in the onset of NETs may help to develop appropriate disease prevention and monitoring strategies.
Methods:
We employed a mediated two-sample Mendelian randomization (MR) approach, analyzing gut microbiota from German studies and NET datasets from the 10th round of the FinnGen project. Mediation analyses were conducted using the metabolites dataset from the Canadian Longitudinal Study of Aging (CLSA) and the TwinsUK study. Instrumental variables were chosen according to established MR criteria and analyzed using the Wald ratio, inverse-variance weighted (IVW), MR-Egger, and weighted median methods. To ensure robustness, sensitivity analyses were performed using Cochrane's Q, Egger's intercept, MR-PRESSO, and leave-one-out methods.
Results:
Causal relationships were identified between the genetic determinants of 6, 5, 2, 1, 2, 3 gut microbiotas and the risk of colorectal, lung, pancreatic, rectum, small intestine, and stomach NETs. Similarly, the genetic determinants of 4, 6, 1, 5, 10, and 7 metabolites were found to be causally related to the risk of colorectal, lung, pancreatic, rectum, small intestine, and stomach NETs, respectively. Through Wald ratio and IVW methods, we preliminarily identified 957 microbiota-metabolite pairs with significant causal associations and formed 13 mediated relationships between the impact of gut microbiotas on NETs.
Conclusion:
Our study suggests that gut microbiotas and its derived metabolites may contribute to the onset of NET, offering a novel insight into the disease's pathogenesis.
Insights
Gut microbes and their metabolites may play a causal role in neuroendocrine tumor (NET) development. This study identifies specific gut microbiota and metabolite links to various NETs, offering new prevention and monitoring insights.
Area of Science:
- Genetics
- Microbiology
- Oncology
Background:
- Neuroendocrine tumors (NETs) are diverse epithelial tumors with unknown origins.
- Understanding gut microbiota and metabolic roles in NETs is crucial for prevention and monitoring.
Purpose of the Study:
- To investigate the causal relationships between gut microbiota, metabolites, and NET risk.
- To explore potential disease prevention and monitoring strategies for NETs.
Main Methods:
- A mediated two-sample Mendelian randomization (MR) approach was used.
- Analyzed gut microbiota (German studies) and NET data (FinnGen project).
- Metabolite data from CLSA and TwinsUK studies were used for mediation analyses.
Main Results:
- Identified causal links between gut microbiota genetic determinants and risks for colorectal, lung, pancreatic, rectum, small intestine, and stomach NETs.
- Found causal relationships between metabolite genetic determinants and risks for these NETs.
- Discovered 957 significant microbiota-metabolite pairs and 13 mediated relationships in NET development.
Conclusions:
- Gut microbiota and their derived metabolites may contribute to NET pathogenesis.
- Provides novel insights into the mechanisms underlying NET development.
- Suggests potential targets for NET prevention and monitoring strategies.
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