Gut microbiota dysbiosis and bone mineral density in hemodialysis patients: The mediating role of immune-metabolic pathways and clinical implications for nursing care.

Gut microbiota community structure significantly differed across BMD tertiles in maintenance hemodialysis patients.

• 165 maintenance hemodialysis patients were included in this single-center prospective cross-sectional study.
• Community structure differences across BMD tertiles were statistically significant (R2 = 0.033, P = 0.003).
• Fecal samples underwent 16S rRNA sequencing and functional prediction.
• BMD was measured via dual-energy X-ray absorptiometry (DXA).

Beta-diversity (PCoA-PC1) was negatively associated with femoral neck BMD, while alpha-diversity (Shannon index) showed a positive association after full adjustment.

• Both associations were statistically significant (P < 0.05) after full covariate adjustment.
• Principal coordinate 1 (PCoA-PC1) was used as the measure of beta-diversity.
• The Shannon diversity index was used as the measure of alpha-diversity.
• These associations were independent of other clinical variables included in the adjusted model.

Fifteen differentially abundant genera were identified between high and low BMD groups.

• The comparison was made between patients in the highest and lowest BMD tertiles.
• Functional prediction revealed short-chain fatty acid (SCFA) pathways were positively associated with BMD.
• Indole/p-cresol pathways showed negative associations with BMD.
• Inflammatory cytokines measured included IL-6 and TNF-α, and gut-derived metabolites included indoxyl sulfate and butyrate.

Immune markers and gut-derived metabolites collectively mediated 45.71% of the relationship between gut microbiota and BMD.

• Mediation analysis was used to quantify the roles of immune markers and gut-derived metabolites.
• The combined mediation proportion was 45.71% of the total microbiota-BMD relationship.
• Mediators assessed included inflammatory cytokines (IL-6, TNF-α) and gut-derived metabolites (indoxyl sulfate, butyrate).
• The remaining portion of the microbiota-BMD association was not explained by these immune-metabolic mediators.

Nursing-modifiable factors significantly modified the association between gut microbiota dysbiosis and BMD.

• The negative relationship between gut microbiota dysbiosis and BMD was strengthened by low fiber intake.
• Severe constipation was identified as a factor that strengthened the negative microbiota-BMD relationship.
• Proton pump inhibitor (PPI) use strengthened the negative association between gut microbiota dysbiosis and BMD.
• Inadequate dialysis, defined as Kt/V < 1.4, also strengthened the negative microbiota-BMD relationship.