Related Experiment Video

Updated: Jul 2, 2025

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
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Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities

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

Shuai Han1,2, Jiapei Gao2, Zi Wang1,2

  • 1Department of Anesthesiology, Northern Jiangsu People's Hospital, Clinical Medical School, Yangzhou University, Yangzhou, China.

Frontiers in Microbiology
|February 23, 2024
PubMed
Abstract

Insights

This study used Mendelian randomization to investigate the causal link between gut microbiota, immune cells, and morphine tolerance (MT). Certain gut bacteria and immune cells were found to influence MT risk, suggesting potential therapeutic targets.

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.
Keywords:
Mendeliancausalitygut microbiotaimmunitymorphine tolerance

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