Accumulating evidence has demonstrated that damages of gut microbiota are strongly associated with central nervous system (
CNS) diseases, such as perioperative
neurocognitive disorders (PND). The present study investigated the role of gut microbial metabolite
short-chain fatty acids (SCFAs) in surgery-induced cognitive deficits and
neuroinflammation in the hippocampus. Adult male C57BL/6J mice received either SCFA mixture or saline orally for 4 weeks, and then partial
hepatectomy was performed. The fecal supernatant of surgical mice was transplanted to normal mice for 3 weeks. The Morris water maze (MWM) and open-field tests were used to evaluate behavioral performance on postoperative or post-
transplantation days 3 and 7. In the MWM test, pretreatment with exogenous SCFAs partially reversed surgery-induced impairments in crossing times and the time spent in the target quadrant on postoperative day 3 (p < 0.05, p < 0.05, respectively). In the open-field test, compared with the surgical mice, exogenous SCFA administration prior to surgery partially improved the locomotor activity (p < 0.05) and anxiety-like behavior (p < 0.05) on postoperative day 3. Surgical
trauma and
anesthesia enhanced ionized
calcium-binding adapter molecule 1 (Iba-1) expression (p < 0.001), increased the levels of
interleukin (IL)-1β (p < 0.001) and
IL-6 (p < 0.001), and inhibited SCFA production (p < 0.001) on postoperative day 3. The expression of the
brain-derived neurotrophic factor (
BDNF) was also decreased (p < 0.001). Overall, surgical
trauma and
anesthesia exacerbated
cognitive impairment, enhanced neuroinflammatory responses, and inhibited SCFA production. Pretreatment with SCFAs attenuated these effects partially by reversing microglial overactivation, inhibiting neuroinflammatory responses, and enhancing
BDNF expression.