Exploring Causal Links Between Gut Microbiota and Geriatric Syndromes: A Two-Sample Mendelian Randomization Analysis.

Background: Both observational studies and clinical trials have demonstrated a link between the gut microbiota and the geriatric syndrome. Nevertheless, the exact nature of this relationship, particularly concerning causality, remains elusive. Mendelian randomization (MR) is a method of inference based on genetic variation to assess the causal relationship between an exposure and an outcome. In this study, we conducted a two-sample Mendelian randomization (TSMR) study to fully reveal the potential genetic causal effects of gut microbiota on geriatric syndromes. Methods: This study used data from genome wide association studies (GWAS) to investigate causal relationships between the gut microbiota and geriatric syndromes, including frailty, Parkinson's disease (PD), delirium, insomnia, and depression. The primary causal relationships were evaluated using the inverse-variance weighted method, MR Egger, simple mode, weighted mode and weighted median. To assess the robustness of the results, horizontal pleiotropy was examined through MR-Egger intercept and MR-presso methods. Heterogeneity was assessed using Cochran's Q test, and sensitivity was evaluated via the leave-one-out method. Results: We identified 41 probable causal relationships between gut microbiota and five geriatric syndrome-associated illnesses using the inverse-variance weighted method. Frailty showed five positive and two negative causal relationships, while PD revealed three positive and four negative causal connections. Delirium showed three positive and two negative causal relationships. Similarly, insomnia demonstrated nine positive and two negative causal connections, while depression presented nine positive and two negative causal relationships. Conclusions: Using the TSMR method and data from the public GWAS database and, we observed associations between specific microbiota groups and geriatric syndromes. These findings suggest a potential role of gut microbiota in the development of geriatric syndromes, providing valuable insights for further research into the causal relationship between gut microbiota and these syndromes.

Multiple reports on the causal relationship between various chronic pain and gut microbiota: a two-sample Mendelian randomization study.

Background: Previous evidence suggests a link between gut microbiota and chronic pain, but the causal relationship is not yet fully understood. Methods: We categorized gut microbiota based on phylum, class, order, family, and genus levels and gathered pain-related information from the UKB and FinnGen GWAS project. Then, we conducted MR analysis to explore the potential causal relationship between gut microbiota and chronic pain at 12 specific locations. Results: We have discovered a direct connection between genetic susceptibility in the gut microbiota (gut metabolites) and pain experienced at 12 specific locations. Notably, Serotonin (5-HT) and Glycine were found to be associated with a higher risk of pain in the extremities. On the other hand, certain microbial families and orders were found to have a protective effect against migraines. Specifically, the family Bifidobacteriaceae (IVW, FDR p = 0.013) was associated with a lower risk of migraines. Furthermore, the genus Oxalobacter (IVW, FDR p = 0.044) was found to be linked to an increased risk of low back pain. Importantly, these associations remained significant even after applying the Benjamini-Hochberg correction test. Our analysis did not find any heterogeneity in the data (p > 0.05), as confirmed by the Cochrane's Q-test. Additionally, both the MR-Egger and MR-PRESSO tests indicated no significant evidence of horizontal pleiotropy (p > 0.05). Conclusion: Our MR analysis demonstrated a causal relationship between the gut microbiota and pain, highlighting its potential significance in advancing our understanding of the underlying mechanisms and clinical implications of microbiota-mediated pain.