Mediating Effects of Immunophenotypes on the Causal Relationship of Gut Microbiota and Their Metabolic Pathways With Osteonecrosis: A Mendelian Randomization Analysis.

BACKGROUND

This study examined the potential causal relationship between gut microbiota and osteonecrosis and analyzed the mediating effects of immunophenotypes to establish evidence-based causal associations.

METHODS

Bayesian weighted Mendelian randomization and the inverse-variance weighted method were used to evaluate the causal relationships between osteonecrosis and 412 gut microbial species and their metabolic pathways, as well as between osteonecrosis and 731 immune cell signatures. Mediation analysis was conducted to assess the role of immune cells in mediating the relationship between gut microbiota and osteonecrosis.

RESULTS

A total of 16 gut microbial species and their metabolic pathways and 23 immunophenotypes were identified as causal factors in susceptibility to osteonecrosis (p < 0.05). The superpathway of sulfate assimilation and cysteine biosynthesis of the gut microbiota demonstrated a protective effect against osteonecrosis. The absolute count of CD33- HLA DR + Myeloid cell exhibited a mediation effect of 4.15%, while T cell %lymphocyte demonstrated a mediation effect of 12.16% in this protective mechanism.

CONCLUSION

The study findings highlighted the role of the superpathway of sulfate assimilation and cysteine biosynthesis of the gut microbiota in exerting a protective effect against osteonecrosis. This protective effect is substantially mediated by a decrease in the absolute count of CD33- HLA DR + Myeloid cell and an increase in T cell % lymphocyte.