Perioperative neurocognitive disorders are common in elderly patients who have undergone surgical procedures. Neuroinflammation induced by microglial activation is a hallmark of these neurological disorders. Acetate can suppress inflammation in the context of inflammatory diseases. We employed an exploratory laparotomy model with isoflurane anesthesia to study the effects of acetate on perioperative neurocognitive disorders in aged mice. Neurocognitive function was assessed with open-field tests and Morris water maze tests 3 or 7 days post-surgery. Acetate ameliorated the surgery-induced cognitive deficits of aged mice and inhibited the activation of IBA-1, a marker of microglial activity. Acetate also reduced expression of inflammatory proteins (tumor necrosis factor-α, interleukin-1β and interleukin-6), oxidative stress factors (NADPH oxidase 2, inducible nitric oxide synthase and reactive oxygen species), and signaling molecules (nuclear factor kappa B and mitogen-activated protein kinase) in the hippocampus. BV2 microglial cells were used to verify the anti-inflammatory effects of acetate in vitro. Acetate suppressed inflammation in lipopolysaccharide-treated BV2 microglial cells, but not when GPR43 was silenced. These results suggest that acetate may bind to GPR43, thereby inhibiting microglial activity, suppressing neuroinflammation, and preventing memory deficits. This makes acetate is a promising therapeutic for surgery-induced neurocognitive disorders and neuroinflammation.

Background: Postoperative gastrointestinal function in uences postoperative recovery and hospital stay length for patients undergoing colorectal surgery. Goal-directed uid therapy (GDFT) restricts uid administration to an amount required to prevent dehydration. Although the uid management of GDFT could decrease the incidence of postoperative complications in patients who undergo high-risk surgery, certain patients may not respond to GDFT. Thus, to achieve optimal treatment, identi cation of patients suitable for GDFT is necessary. Accordingly, in this study, we evaluated the predictive capacity of metabolomics pro ling for postoperative recovery after surgery for colorectal cancer. Methods: Metabolomic pro ling of 48 patients with colorectal cancer who underwent surgery was performed. Patients were divided into delayed-and enhanced-recovered groups based on gastrointestinal function within 72 hours, and the results of-omics analysis showed differential serum metabolites between the two groups of patients in the postanesthesia care unit 24 hours after surgery. A support vector machine model was applied to evaluate the curative effects of GDFT in different patients. Results: Four metabolites, oleamide, ubiquinone-1, acetylcholine, and oleic acid, were found to be highly associated with postoperative gastrointestinal function and could serve as potential biomarkers. Moreover, four pathways were found to be highly related to postoperative gastrointestinal recovery. Among these, the vitamin B6 metabolism pathway may be a common pathway for improving postoperative recovery in various diseases. Conclusion: Our ndings proposed a novel method to predict postoperative recovery of gastrointestinal function based on metabolomic pro ling and suggested the potential mechanisms contributing to gastrointestinal function after surgical resection of colorectal cancer under the uid management of GDFT.

Nutrition support is essential for surgical patients. Patients undergoing pancreaticoduodenectomy (PD) require tremendous nutrient support but also faced with risks of infection and gastrointestinal complications. Early parenteral nutrition has recently shown benefits while limited information provided about the influence on metabolism. This prospective single-center cohort study used plasma metabolomics to clarify metabolic alteration after early parenteral nutrition followed with enteral nutrition. Patients undergoing pancreaticoduodenectomy (n = 52) were enrolled. 36 patients received parenteral nutrition within 3 days postoperatively followed with EN (TPN group), 16 patients received standard fluids followed with EN (GIK group). We found that the weight loss is reduced in TPN group while the other clinical outcomes and inflammatory cytokines showed no statistical significance. The TPN group showed significance in amino acids, lipid, and phospholipids metabolism compared with the GIK group. Moreover, integration analysis indicated that early TPN could promote the metabolism of long-chain fatty acids, phospholipids, ketone bodies, and branched-chain amino acids. We conclude that early TPN support followed with EN for patients undergoing PD reduced the perioperative weight loss and promoted the metabolic transition to anabolic metabolism with the recovery of lipid metabolism, suggesting its benefits for the recovery of patients.