Effects of prebiotic galacto-oligosaccharide on postoperative cognitive dysfunction and neuroinflammation through targeting of the gut-brain axis

摘要

Surgery-induced neuroinflammation plays an important role in postoperative cognitive dysfunction (POCD). Gut microbiota is a key regulator of neurological inflammation. Nurturing with prebiotics is an effective microbiota manipulation that can regulate host immunity and cognition. The aim of the present study was to test whether administration of the prebiotic Bimuno? (galactooligosaccharide (B-GOS) mixture) could ameliorate POCD and attenuate surgery-induced neuroinflammation through the microbiota-brain-axis. Adult rats undergoing abdominal surgery under isoflurane anesthesia were fed with water or prebiotic B-GOS supplementation (15?g/L) for 3?weeks. Novel objective recognition task was employed for testing cognitive changes on postoperative day three. Expression of microglial marker Iba-1 in the hippocampus was assessed by immunohistochemical staining. Expression levels of phenotypic gene markers of activated microglia (M1: iNOS, CD68, CD32; M2: Ym1, CD206, and SOCS3) in hippocampus were determined by quantitative polymerase chain reaction (qPCR). Inflammatory cytokines in the hippocampus were assessed using enzyme-linked immunosorbent assay (ELISA). Feces were collected for microbial community analysis. Rats exhibited an impairment in novel objective recognition 3?days after surgery compared with control rats (P??.01). In the hippocampus, expressions of Iba-1 and M1 markers of surgical rats were significantly upregulated. Similarly, expressions of SOCS3 and CD206 in the hippocampus were upregulated. Additionally, increasing levels of IL-6 and IL-4 were evident in the hippocampus. Administration of B-GOS significantly alleviated cognitive decline induced by surgery (P??.01). B-GOS-fed rats showed a significantly downregulated activation of microglia and expressions of M1-related genes and SOCS3 and IL-6. While there was no significant difference in expressions of CD206 and Ym1 and IL-4 between the surgical and B-GOS groups. Analysis of gut microbiome found that administration of B-GOS induced a significant change beta diversity of the gut microbiome and proliferation of Bifidobacterium and other potentially anti-inflammatory microbes. Administration of B-GOS has a beneficial effect on regulating neuroinflammatory and cognitive impairment in a rat model of abdominal surgery and was associated with the manipulation of gut microbiota.