Gut-brain axis disruption, intestinal barrier damage, and systemic inflammation as predictors of POCD after...

Postoperative cognitive dysfunction (POCD) is a common complication following cholecystectomy, and the full pathogenesis remains multifactorial. Accumulating evidence suggests that the gut-brain axis plays a critical role in the development of POCD, but the specific relationship linking intestinal barrier dysfunction, systemic inflammation, and cognitive impairment has not been quantitatively characterized in cholecystectomy patients.

This prospective nested case-control study enrolled 361 consecutive patients scheduled for elective cholecystectomy. Patients with POCD were identified using the Reliable Change Index (RCI). 24 POCD patients were matched 1:2 with 48 non-POCD controls. Serum levels of lipopolysaccharide-binding protein (LBP), interleukin-6 (IL-6), TNF-α, and neuronal injury markers were detected.

24 (6.7%) developed POCD. Baseline characteristics were well balanced. POCD patients exhibited dysregulated gut-brain axis biomarkers and a more pronounced, sustained postoperative inflammatory response. Multivariate regression analysis identified postoperative LBP (per 1 μg/mL increase; aOR = 1.08, 95%CI = 1.03-1.13, p = 0.001), peak postoperative IL-6 (per 1 pg/mL increase; aOR = 1.02, 95%CI = 1.01-1.03, p < 0.001), and peak postoperative TNF-α as independent risk factors for POCD. Higher preoperative MMSE score was a protective factor (aOR = 0.85, 95%CI = 0.73-0.99, p = 0.038). A greater decline in ΔMMSE was associated with an increased POCD risk.

This study confirms a stable and independent association between intestinal leakage, systemic inflammation, and POCD following cholecystectomy. LBP and IL-6 are key biomarkers in this pathway, with high predictive value for POCD risk. The gut-brain axis drives postoperative neuroinflammation, thus supporting targeted strategies for the prevention and treatment of POCD.