Guanglei Chen
Yaxian Jin
*
Yuhao Zheng
The final, formatted version of the article will be published soon.
ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Microorganisms in Vertebrate Digestive Systems
Volume 15 - 2024 |
doi: 10.3389/fmicb.2024.1414977
Genetic Prediction of Blood Metabolites Mediating the Relationship Between Gut Microbiota and Alzheimer's Disease: A Mendelian Randomization Study
Provisionally accepted- Guizhou University of Traditional Chinese Medicine, Guiyang, China
Background: Observational studies have suggested an association between gut microbiota and Alzheimer's disease (AD); however, the causal relationship remains unclear, and the role of blood metabolites in this association remains elusive. Purpose: To elucidate the causal relationship between gut microbiota and AD and to investigate whether blood metabolites serve as potential mediators. Results: After adjustment for reverse causality and MVMR correction, class Actinobacteria (OR: 1.03, 95% CI: 1.01-1.06, P = 0.006), family Lactobacillaceae (OR: 1.03, 95% CI: 1.00-1.05, P = 0.017), genus Lachnoclostridium (OR: 1.03, 95% CI: 1.00-1.06, P = 0.019), genus Ruminiclostridium9 (OR: 0.97, 95% CI: 0.94-1.00, P = 0.027) and genus Ruminiclostridium6 (OR: 1.03, 95% CI: 1.01-1.05, P = 0.009) exhibited causal effects on AD. Moreover, 1-ribosyl-imidazoleacetate levels (-6.62%), Metabolonic lactone sulfate levels (2.90%), and Nonadecanoate (19:0) levels (-12.17%) mediated the total genetic predictive effects of class Actinobacteria on AD risk. Similarly, 2-stearoyl-GPE (18:0) levels (-9.87%), Octadecanedioylcarnitine (C18-DC) levels (4.44%), 1-(1-enyl-stearoyl)-2-oleoyl-GPE (p-18:0/18:1) levels (38.66%), and X-23639 levels (13.28%) respectively mediated the total genetic predictive effects of family Lactobacillaceae on AD risk. Furthermore, Hexadecanedioate (C16-DC) levels (5.45%) mediated the total genetic predictive effects of genus Ruminiclostridium 6 on AD risk; Indole-3-carboxylate levels (13.91%), X-13431 levels (7.08%), Alpha-ketoglutarate to succinate ratio (-13.91%), 3-phosphoglycerate to glycerate ratio (15.27%), and Succinate to proline ratio (-14.64%) respectively mediated the total genetic predictive effects of genus Ruminiclostridium 9 on AD risk. Conclusion: Our mediation MR analysis provides genetic evidence suggesting the potential mediating role of blood metabolites in the causal relationship between gut microbiota and AD. Further large-scale randomized controlled trials are warranted to validate the role of blood metabolites in the specific mechanisms by which gut microbiota influence AD.
Keywords: Gut Microbiota, Blood metabolites, Alzheimer's disease, Mendelian randomization, Two-step mendelian randomization, Univariable Mendelian Randomization, multivariable Mendelian randomization
Received: 10 Apr 2024; Accepted: 22 Jul 2024.
Copyright: © 2024 Chen, Jin, Chu, Zheng, Chen and Zhu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yaxian Jin, Guizhou University of Traditional Chinese Medicine, Guiyang, China
Cancan Chu, Guizhou University of Traditional Chinese Medicine, Guiyang, China
Yunzhi Chen, Guizhou University of Traditional Chinese Medicine, Guiyang, China
Xing Zhu, Guizhou University of Traditional Chinese Medicine, Guiyang, China
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