Establishment and evaluation on a rat model of postoperative delirium induced by cardiopulmonary bypass with human gut microbiota

Objective To establish a rat model of postoperative delirium (POD) induced by cardiopulmonary bypass with human gut microbiota using fecal microbiota transplantation (FMT) technology, and evaluate the model based on bioinformatics, cytokine analysis, and behavioral testing methods.

Methods SPF-grade adult male SD rats weighing 400 to 450 g were selected. After undergoing a week of Morris water maze training, rats with consistent performance were used to construct pseudo-germ-free rat models. Subsequently, 20 successfully modeled rats were randomly divided into two groups: (CON group receiving fecal microbiota filtrate from healthy individuals) and (POD group receiving fecal microbiota filtrate from POD patients). Behavioral tests were conducted two weeks after modeling, and rat feces were collected for metagenomic sequencing. Rats were euthanized by cervical dislocation, and blood and brain tissue samples were collected for cytokine and histopathological examinations.

Results Compared with the CON group, the POD group exhibited significantly increased relative abundances of Akkermansiaceae, Prevotellaceae, and Akkermansia muciniphila, while the relative abundances of Lactobacillaceae and Mediterraneibacter massiliensis decreased significantly (P < 0.05). Serum levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were significantly higher in the POD group than those in the CON group (P < 0.05). Hematoxylin-eosin (HE) staining in the POD group revealed neurons with pyknotic and hyperchromatic nuclei. After modeling, the average latency in the Morris water maze was significantly longer in the POD group than that in the CON group (P < 0.05).

Conclusion This study utilizes fecal microbiota transplantation technology to establish a rat model of POD induced by cardiopulmonary bypass with human gut microbiota. The changes in gut microbiota structure abundance, levels of POD-related inflammatory factors, and Morris water maze test results in this model are similar to the clinical manifestations observed in patients with POD induced by cardiopulmonary bypass.