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This study aims to explore the causal relationship between gut microbiota and frailty using Mendelian randomization (MR) methods and assess the potential mediating or masking effects of immune cells in this relationship.
Genome-wide association study data for 473 gut microbiota taxa, 731 immune cell characteristics, and frailty were extracted from the GWAS Catalog. A two-sample MR approach was employed to evaluate the causal relationship between gut microbiota and frailty. To identify the mediating or masking effects of immune cells, a two-step MR strategy was applied, and reverse MR analysis was conducted to validate the unidirectional nature of the causal mediation pathway (gut microbiota →immune cells → frailty).
The study found that 4 gut microbiota taxa and 17 immune cell characteristics had causal associations with frailty. Mediation analysis revealed two causal mediation pathways: phylum Firmicutes A → CD28+ CD45RA+ CD8br AC → frailty, and species Lachnospira rogosae → CD62L-CD86 + myeloid DC %DC → frailty. Immune cell characteristics acted as masking effects in both pathways, and reverse MR analysis supported the unidirectional nature of these causal relationships.
The causal associations and mediation effects identified in this study provide a theoretical basis and direction for the development of frailty management strategies based on gut microbiota and immune cells.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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