Causal association between gut microbiota and osteonecrosis in European populations: a two-sample Mendelian...

Recent studies have linked gut microbiota composition to osteonecrosis, but the causal relationship remains unclear. Clarifying this relationship is clinically important because osteonecrosis currently lacks early biomarkers and etiology-targeted therapies; if causal, the gut microbiome would offer a readily modifiable intervention target.

We conducted a two-sample Mendelian randomization analysis to explore this relationship. Exposure data were sourced from the MiBioGen consortium (N = 18,340), while outcome data on osteonecrosis were obtained from FinnGen (N = 392,580). The Inverse Variance Weighted method was used as the primary analytical approach, supplemented by comprehensive sensitivity analyses to assess the robustness of our findings.

Our analysis screened 196 microbial taxa and identified seven taxa associated with osteonecrosis risk in European populations. Protective effects were noted for the genus Odoribacter (OR = 0.579; P = 0.027) and family Alcaligenaceae (OR = 0.703; P = 0.049). Conversely, increased risk was linked to the genus Eubacterium fissicatena group (OR = 1.272; P = 0.046), genus Bifidobacterium (OR = 1.372; P = 0.038), order Bifidobacteriales (OR = 1.412; P = 0.023), family Bifidobacteriaceae (OR = 1.412; P = 0.023) and phylum Actinobacteria (OR = 1.750; P = 0.001). Sensitivity analyses confirmed the robustness of these findings, with no evidence of pleiotropy or heterogeneity.

This study establishes a causal link between gut microbiota composition and osteonecrosis, suggesting that gut microbiota may be a modifiable factor in its pathogenesis. Further research is needed to elucidate underlying mechanisms and evaluate microbiota-targeted interventions for prevention and treatment.