Perioperative neurocognitive dysfunction (PND) refers to alterations in cognitive function before and/or after surgery, which are clinically manifested by abnormalities of learning, memory, language, thinking, spirit, and emotions. Postoperative delirium and postoperative cognitive dysfunction are included in PND, which has a higher incidence in elderly patients and leads to longer hospital stays, higher costs, greater social burdens, and increased mortality. Previously, it was assumed that cognition is controlled only by the central nervous system, but recent research indicates that various factors, including gut microbiota, significantly influence cognitive function and neurological health by affecting brain structure, vascular physiology, and blood-brain barrier permeability. The aim of the study is to investigate the impact of probiotics on gut microbiota and their potential role in postoperative neurocognitive dysfunction in patients undergoing total hip and knee replacement surgeries.

The study will be conducted in the Department of Anaesthesiology, Pain Medicine and Critical Care, AIIMS after obtaining the institutional ethics committee approval. Patients above 60 years undergoing total hip or knee arthroplasty under general anaesthesia will be recruited after obtaining an informed consent. The patient who does not meet the inclusion criteria and or not willing to participate in the study will be excluded from the study. The recruited patients will be classified in two groups Group A (Probiotic group) and Group B (Control group). The drug will be used from 2 weeks before operation until 2 weeks postoperatively. The probiotic group will be treated with Probiotic capsules containing Lactobacillus Acidophilus twice a day (2 billions CFU/ day) while the control group will be treated with placebo capsules containing Calcium 500mg twice a day in the same package. The drug and placebo will be similar in size, shape and smell. The drug will be taken orally, twice a day, and the postoperative cognitive function will be evaluated using a neuropsychological test. If participants request to withdraw from the trial, we will discontinue the allocated intervention for the given trial participants. The baseline assessment, demographic details, medical history, history of neurological deficit of the patients will be recorded in the data collection form. All patients will receive standard anesthesia care. At recovery room, the vitals and the oxygen saturation of the patient are regularly monitored every fifteen minutes. Stool samples will be collected at three different times: 24 hours prior to surgery, 24 hours after Surgery and 2 week after surgery. The samples will be kept in a sterilized container and stored in a refrigerator or freezer until they are picked up or brought to the study site. The collected stool samples will be sent to laboratory for detailed analysis of the bacteria and other microorganisms present in the gut. Metagenomic analysis will allows comprehensive profiling of microbial communities and their functional capabilities, providing insights into how gut microbiota changes related to PND.  Descriptive and non-parametric statistical analysis would be carried out to analyse the data. The data would be analysed through SPSS 26.0 version or any other standard bio statistical software. Bioinformatics analysis will be done for the prediction of known and novel variants. Any variant with a P value < 0.05 will be considered significant.

By employing advanced metagenomic techniques, this research seeks to identify specific microbial taxa associated with PND and assess changes in gut microbiota post-anesthesia and surgery. The findings will provide preliminary data on microbial signatures linked to PND, inform future therapeutic strategies, and establish the feasibility of larger-scale studies, potentially leading to innovative, non-invasive interventions to improve postoperative cognitive outcomes and patient quality of life