Genetically supported causality between gut microbiota, immune cells and morphine tolerance: a two-sample Mendelian...

Area of Science:

• Genetics
• Immunology
• Microbiology

Background:

• Previous research suggests a link between gut microbiota/immune cells and morphine tolerance (MT).
• The causal relationship between these factors and MT remains uncertain.
• Investigating this association is crucial for understanding MT development.

Purpose of the Study:

• To investigate the causal association between gut microbiota/immune cells and morphine tolerance (MT).
• To reveal the impact of gut microbiota/immune cells on the risk of developing MT.
• To utilize a two-sample Mendelian randomization (MR) study for causal inference.

Main Methods:

• Employed two-sample Mendelian randomization (MR) using genome-wide association study (GWAS) summary statistics.
• Utilized inverse variance-weighted (IVW) method as the primary analysis approach.
• Applied MR-PRESSO, MR-Egger regression, Cochran's Q-test, and leave-one-out analysis to ensure robustness and assess pleiotropy and heterogeneity.

Main Results:

• Identified 6 gut microbial taxa and 16 immune cells causally related to MT.
• Found 2 bacterial features and 9 immunophenotypes associated with a lower risk of MT.
• Detected 4 bacterial features and 7 immunophenotypes significantly associated with an increased MT risk.
• Confirmed robustness of findings through heterogeneity, pleiotropy, and sensitivity analyses.

Conclusions:

• Confirmed a potential causal link between gut microbiota, immune cells, and MT.
• Elucidated potential mechanisms by which gut microbiota and immune cells contribute to MT.
• Provided a foundation for developing targeted prevention strategies for MT.