Association of gut microbiota and arginine-agmatine metabolism with postoperative delirium in elderly patients following lower limb fracture surgery: a prospective nested case-control study.

OBJECTIVE

This study aimed to investigate the role of gut microbiota and arginine-agmatine metabolic levels in the pathogenesis of postoperative delirium (POD) in elderly patients following lower limb fracture surgery.

METHODS

This prospective nested case-control study enrolled 111 patients aged ≥65 years who were scheduled for elective lower limb orthopedic surgery. POD was assessed twice daily (08:00-10:00 and 18:00-20:00) using the Confusion Assessment Method-Chinese Reversion (CAM-CR). Thirty patients who developed POD were matched to thirty non-POD patients via propensity score matching (PSM). Fecal samples collected one day preoperatively underwent gut microbiota analysis using 16S rRNA gene sequencing, with α-diversity, β-diversity, and linear discriminant analysis effect size (LEfSe) analyses performed. Additionally, fasting venous blood samples collected one day preoperatively were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to quantify plasma levels of arginine, agmatine, putrescine, spermidine, and spermine. Spearman correlation analysis was performed to explore associations between differential bacterial genus abundance, arginine-agmatine metabolite levels, and CAM-CR scores.

RESULTS

Compared to controls, the POD group showed significantly altered gut microbiota β-diversity (P < 0.001) but no change in α-diversity. At the genus level, LEfSe analysis revealed increased abundance of Megasphaera and Clostridium innocuum group, and decreased abundance of Paraprevotella and Akkermansia in the POD group. Additionally, the POD group exhibited significantly elevated arginine levels (P = 0.044) and reduced agmatine (P = 0.016) and spermine (P = 0.005) levels. Correlation analysis demonstrated that arginine levels were positively correlated with Megasphaera abundance and CAM-CR score, but negatively correlated with Paraprevotella and Akkermansia abundance; agmatine concentrations were positively correlated with Akkermansia abundance but negatively correlated with CAM-CR score; putrescine levels were negatively correlated with Clostridium innocuum group abundance; spermine levels were positively correlated with Paraprevotella abundance but negatively correlated with CAM-CR score. CAM-CR score was negatively associated with Akkermansia abundance and positively associated with Megasphaera abundance (all P < 0.05).

CONCLUSIONS

Gut microbiota and arginine-agmatine metabolism are associated with the pathogenesis of POD in elderly lower limb fracture patients, though their precise mechanistic roles require further investigation.