Sleep dysfunction and gut dysbiosis-related amino acid metabolism disorders in cynomolgus monkeys after middle cerebral artery occlusion

This study explored the characteristics of post-stroke sleep dysfunction and verified its association with gut probiotic dysbiosis-related amino acid metabolism disorders using fecal microbiota transplantation (FMT) in a non-human primate stroke model. Twenty adult male cynomolgus monkeys were divided into sham (n = 4), middle cerebral artery occlusion (MCAO, n = 5), MCAO + FMT (n = 3), and donor (n = 8) groups. The MCAO + FMT group received FMT 4 weeks post-MCAO. Sleep parameters, gut microbiota, gamma-aminobutyric acid (GABA), and glutamine in the cerebrospinal fluid (CSF) were measured at baseline and 4, 8, and 12 weeks postoperatively. At 4, 8, and 12 weeks postoperatively, the MCAO group showed decreased sleep efficiency, lower relative abundance of Lactobacillus, and reduced GABA in the CSF compared with the sham group. Sleep efficiency at 4 and 8 weeks post-FMT and GABA concentration in the CSF at 4 weeks post-FMT were higher in the MCAO + FMT group than in the MCAO group. Post-stroke sleep dysfunction in monkeys is characterized by impaired sleep coherence, associated with decreased levels of probiotics such as Lactobacillus, GABA, and glutamine in the CSF, and can be ameliorated using FMT.

本研究旨在探究卒中后睡眠功能障碍的特征，并通过在非人灵长类卒中模型中实施粪便菌群移植（fecal microbiota transplantation, FMT），验证其与肠道益生菌失调相关氨基酸代谢紊乱的关联。本研究选取20只成年雄性食蟹猴，分为假手术（sham, n=4）组、大脑中动脉闭塞（middle cerebral artery occlusion, MCAO, n=5）组、MCAO+FMT（n=3）组以及供体（n=8）组。MCAO+FMT组于卒中造模后4周接受粪便菌群移植干预。分别于基线期、术后4周、8周及12周检测睡眠参数、肠道菌群、脑脊液（cerebrospinal fluid, CSF）中γ-氨基丁酸（gamma-aminobutyric acid, GABA）与谷氨酰胺水平。术后4、8、12周时，与假手术组相比，MCAO组食蟹猴的睡眠效率降低，乳酸杆菌（Lactobacillus）相对丰度下降，脑脊液中γ-氨基丁酸水平降低。MCAO+FMT组在粪便菌群移植后4周、8周的睡眠效率，以及移植后4周的脑脊液γ-氨基丁酸浓度，均高于MCAO组。食蟹猴卒中后睡眠功能障碍以睡眠连贯性受损为特征，其发病与乳酸杆菌等益生菌丰度降低、脑脊液中γ-氨基丁酸及谷氨酰胺水平下降密切相关，且可通过粪便菌群移植得到改善。