Perioperative probiotic treatment decreased the incidence of postoperative cognitive impairment in elderly patients following non-cardiac surgery: A randomised double-blind and placebo-controlled trial.

BACKGROUND: Given that population aging is a global health challenge, the high prevalence of postoperative neurocognitive impairment in elderly patients necessitates the development of novel simple and effective prevention methods. OBJECTIVE: To evaluate the effects of perioperative application of oral probiotic as a prophylaxis for cognitive impairment in elderly patients following non-cardiac surgery. METHODS: This randomised double-blind and placebo-controlled trial included 120 elderly patients (in a modified intention-to-treat analysis) scheduled for elective orthopaedic or colorectal surgery. Patients were assigned to receive either probiotics or a placebo from hospital admission until discharge. The primary endpoint was the incidence of postoperative cognitive impairment, defined as a decrease of ≥3 points in the Mini-Mental State Examination (MMSE) scores from admission baseline to the 7th day post-surgery. Secondary endpoints included changes in plasma interleukin-6 (IL-6) and cortisol, postoperative pain intensity, postoperative sleep quality, gastrointestinal function recovery, and faecal microbiota composition. RESULTS: The incidence of postoperative cognitive impairment in the probiotic group was significantly lower than in the control group (3 of 59 patients [5.1%] vs. 10 of 61 patients [16.4%], P = 0.046). In addition, compared to pre-surgery, the levels of plasma IL-6 and cortisol in the probiotic group decreased more than in the control group 5-7 days after surgery (IL-6: -117.90 ± 49.15 vs. -14.93 ± 15.21, P = 0.044; cortisol: -158.70 ± 53.52 vs. 40.98 ± 72.48, P = 0.010). Relative abundance at the genus level in the faeces of the probiotic group also changed more than in that of the control group during the perioperative period. In contrast, postoperative pain intensity, sleep quality, and gastrointestinal function recovery did not differ significantly between the two groups. CONCLUSION: Perioperative application of oral probiotic prevents postoperative cognitive impairment in elderly patients following non-cardiac surgery, possibly via the limitation of peripheral inflammation and the stress response.

Intestinal dysbacteriosis mediates the reference memory deficit induced by anaesthesia/surgery in aged mice.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is associated with increased morbidity and mortality and has become a major concern for patients and caregivers. POCD is most common in older patients. Previous studies demonstrated that the gut microbiome affects cognitive function and behaviour, and perioperative factors, including the operation itself, antibiotics, opioids or acid-inducing drugs, affect the gut microbiome. Thus, we hypothesised that intestinal dysbacteriosis caused by anaesthesia/surgery induces POCD. METHODS: Tibial fracture internal fixation was performed in 18-month-old C57BL/6 mice under isoflurane anaesthesia to establish the POCD model. The Morris water maze was used to measure reference memory after anaesthesia/surgery. High-throughput sequencing of 16S rRNA from faecal samples was used to investigate changes in the abundance of intestinal bacteria after anaesthesia/surgery. To confirm the role of the gut microbiome in POCD, we pretreated mice with compound antibiotics or mixed probiotics (VSL#3). Anaesthesia/surgery impaired reference memory and induced intestinal dysbacteriosis in aged mice. RESULTS: The 16S rRNA sequencing data revealed 37 genera (18 families) of bacteria that changed in abundance after anaesthesia/surgery. Pretreating mice with compound antibiotics or mixed probiotics (VSL#3) prevented the learning and memory deficits induced by anaesthesia/surgery. We further conducted quantitative real-time polymerase chain reaction (qRT-PCR) of 22 common types of bacteria among the 37 total types to verify the results of bacterial flora changes after anaesthesia/surgery. Numbers of 8 types of bacteria changed after anaesthesia/surgery but returned to normal after treatment with a mix of probiotics. CONCLUSIONS: Our data suggest that deficits in reference memory induced by anaesthesia/surgery are mediated by intestinal dysbacteriosis.