The Gut–Brain Axis in the Pathogenesis of Postoperative Cognitive Dysfunction: Literature Review

Abstract

Postoperative cognitive dysfunction (POCD) is a pressing issue in modern surgical practice, particularly among older patients undergoing extensive abdominal, including colorectal, surgery. Impairments of memory, attention, executive function, and processing speed that emerge after surgery can significantly reduce patients' quality of life, prolong hospitalization, and hinder full recovery. The pathogenesis of POCD is multifactorial and involves the perioperative stress response, systemic inflammation, endothelial dysfunction, and disruption of the body's barrier systems. Contemporary views on the mechanisms of this condition extend beyond purely neurogenic concepts: increasing attention is being paid to the role of the intestinal barrier and the gut–brain axis as an independent and still insufficiently characterized link in its pathogenesis.
The purpose of the study is to systematize current data on the pathogenesis of postoperative cognitive dysfunction, with a focus on the role of the intestinal barrier and the gut–brain axis as key but insufficiently characterized links in this process.
Methods. A targeted literature search was conducted in PubMed, eLibrary, and Google Scholar databases for the period from 2010 to 2025 using the following keywords: postoperative cognitive dysfunction, gut–brain axis, intestinal barrier, colorectal surgery, surgical stress, general anesthesia, intestinal permeability. A total of 33 sources were selected and analyzed. The review sequentially addresses the general links in POCD pathogenesis — the perioperative stress response, systemic inflammation, endothelial dysfunction, disruption of the blood–brain and intestinal barriers, neuroinflammation, and neurometabolic shifts — as well as the humoral, neural (vagal), and neuroendocrine pathways of the gut–brain axis. Particular attention is given to biomarkers of intestinal barrier dysfunction (zonulin, claudin-3, I-FABP, citrulline) and their association with the systemic inflammatory response.
Conclusion. The intestinal barrier represents an important and relatively underappreciated link in the pathogenesis of postoperative cognitive dysfunction. Its disruption can initiate and sustain systemic inflammation, increase blood–brain barrier permeability, and affect central nervous system function via the gut–brain axis, warranting further investigation of this pathway as a potential therapeutic target, including in patients undergoing colorectal surgery.