Abstract: Background　Intestinal microorganisms play a significant role in regulating host metabolism and dietary lipid metabolism.Recent studies have showed that schizophrenia is associated with lipid metabolism disorders and gut microbial dysbiosis to some degree.However，rare studies in China are focused on the characteristics of gut microbial metabolism and serum lipid metabolism in patients with schizophrenia at different stages. Objective　To study the changes of serum lipid and gut microbial metabolism in patients with schizophrenia，and further explore their influence on the disease. Methods　Forty-two schizophrenic patients in acute stage（acute group），41 schizophrenic patients in remission stage（remission group）and 40 healthy volunteers（healthy control group）were recruited from Anhui Mental Health Center from November 2018 to July 2019.General demographic information including gender，age，height，weight，BMI，and duration of schizophrenia were collected.Clinical symptoms of schizophrenia were assessed by the Positive and Negative Syndrome Scale（PANSS）. The blood sample was collected to measure the levels of total cholesterol（TC），high-density lipoprotein（HDL），triglyceride（TG），apolipoprotein A1（APOA1），apolipoprotein B1（APOB1）. The stool sample was collected to detect the characteristics of microbial metabolism by using the liquid chromatography-mass spectrometry.And the association of microbial metabolism and blood lipid levels with schizophrenia was explored. Results　The average scores of cognitive，excitement，and depression factors，positive and negative subscales and PANSS scale in acute group were higher than those in remission group（P<0.05）.The healthy control group had higher average levels of HDL and APOA1 than both remission and acute groups（P<0.05）.The average level of TG in remission group was higher than that in acute group or healthy control group（P<0.05）.There was a negative correlation between TC level and depression factor score in acute group（P<0.05）. There was a negative correlation between HDL level and negative subscale score in remission group（P<0.05）. The APOA1 level was positively correlated with the positive subscale score（P<0.05），and negatively correlated with the negative subscale score（P<0.05）.Compared with the control group，both acute and remission groups showed significantly changed overall microbial metabolic composition，and notably different lipid metabolism pathways such as steroid hormone synthesis，sphingolipid metabolism，cortisol synthesis and secretion，ovarian steroid production and regulation of fat metabolism in adipocytes（P<0.05）. Moreover，acute group also demonstrated abnormal biosynthesis of unsaturated fatty acid，linoleic acid metabolism and arachidonic acid metabolism pathway. Conclusion　Some abnormal changes in blood lipid and microbial metabolism were found in both acute and remission schizophrenic patients，of which dyslipidemia may be associated with schizophrenic symptoms，and the abnormal lipid metabolism of microorganisms may further affect the lipid metabolism process of the host，both of them are high risk factors for schizophrenia and should be valued in further research and diagnosis and treatment.

Key words: Schizophrenia, Gastrointestinal microbiome, Lipid metabolism, Liquid chromatography-mass spectrometry, Metabolomics, Acute stage, Remission stage

摘要： 背景　肠道菌群在调节宿主新陈代谢和饮食来源的脂质代谢中具有重要作用。近年来研究发现，精神分裂症与脂质代谢紊乱及肠道菌群异常均有一定关联，但目前国内针对不同时期精神分裂症患者的肠道菌群代谢与血清脂质代谢特征的研究仍较少。目的　研究精神分裂症患者血脂及相应肠道菌群代谢改变，并探讨两者对疾病的影响。方法　纳入2018年11月—2019年7月安徽省精神卫生中心住院的精神分裂症急性期患者42例（急性期组），缓解期患者41例（缓解期组），志愿招募匹配的健康人40例（健康对照组）为研究对象，收集其性别、年龄、身高、体质量、体质指数（BMI）、患者病程等一般资料，并采用阳性和阴性综合征量表（PANSS）评估患者临床症状，并收集血液和粪便标本，检测总胆固醇（TC）、高密度脂蛋白（HDL）、三酰甘油（TG）、载脂蛋白A1（APOA1）、载脂蛋白B1（APOB1）。采用液相色谱-质谱分析法分析菌群代谢特征并比较3组间的差异性，探讨肠道菌群代谢及血脂水平改变对精神分裂症的影响。结果　急性期组的认知因子、兴奋因子、抑郁因子、阳性因子、阴性因子评分及PANSS总分高于缓解期组（P<0.05）。缓解期组、急性期组的HDL、APOA1水平低于健康对照组（P<0.05）；缓解期组TG水平高于急性期组、健康对照组（P<0.05）。急性期精神分裂症患者TC水平与抑郁因子评分呈负相关（P<0.05）。缓解期精神分裂症患者HDL水平与阴性因子评分呈负相关（P<0.05）；缓解期精神分裂症患者APOA1水平与阳性因子评分呈正相关（P<0.05），与阴性因子评分呈负相关（P<0.05）。与对照组相比，精神分裂症患者整体肠道菌群代谢组成发生改变，在相关脂质代谢通路如类固醇激素的合成、鞘脂代谢、皮质醇的合成与分泌、卵巢类固醇生成及调节脂肪细胞中的脂肪代谢等通路存在差异（P<0.05）；精神分裂症急性期患者不饱和脂肪酸的生物合成、亚油酸代谢、花生四烯酸代谢通路存在异常。结论　不同时期的精神分裂症患者均存在部分血脂和肠道菌群代谢的改变，其中血脂异常与疾病症状具有相关性，肠道菌群的脂质代谢异常则可能进一步影响宿主脂质代谢过程，两者均是精神分裂症的高危险因素，应在今后的研究和诊疗中加以重视。

关键词: 精神分裂症, 胃肠道微生物组, 脂质代谢, 液相色谱-质谱分析, 代谢组学, 急性期, 缓解期