肠道菌群与叶酸的关联对首发未用药精神分裂症患者精神症状的影响

Effect of the correlation between gut microbiota and folic acid in first-episode schizophrenia

目的探讨肠道菌群、叶酸及两者的关联性对首发未用药精神分裂症(SCZ)患者精神症状的影响。方法选取2018年3月至2019年12月郑州大学第一附属医院首发未用药SCZ患者100例(SCZ组)和健康对照者90名(健康对照组),采用电化学发光法测定血清中叶酸水平,采用阳性和阴性症状量表(PANSS)评定SCZ组精神症状,采用认知功能成套测验(MCCB)评估认知功能。采集粪便样本提取细菌DNA,进行16S rRNA测序。探索SCZ患者肠道菌群和叶酸对精神症状和认知功能的影响。结果SCZ组纳入男41例,女59例,年龄(22.6±8.2)岁;健康对照组纳入男32名,女58名,年龄(23.0±3.0)岁。SCZ组血清叶酸水平低于健康对照组[M(Q1,Q3)][6.92(4.98,8.49)μg/L比8.93(7.13,13.37)μg/L](P<0.001)。SCZ组肠道菌群中双歧杆菌属[0.005(0.003,0.013)比0.014(0.004,0.031)]和拟杆菌属相对丰度[0.015(0.001,0.091)比0.083(0.029,0.193)]低于健康对照组(均P<0.001)。与健康对照组相比,SCZ组在认知功能的七大维度的评分下降明显(均P<0.05)。SCZ组血清叶酸水平与PANSS中阴性症状分呈负相关(r=-0.378,P<0.001),与信息处理速度(r=0.310,P=0.011)呈正相关。SCZ组双歧杆菌属相对丰度与血清叶酸水平呈正相关(r=0.374,P<0.001),与一般精神病理分呈负相关(r=-0.326,P=0.001),与信息处理速度呈正相关(r=0.330,P=0.003)。多重线性回归分析结果显示SCZ患者叶酸×双歧杆菌属交互项与一般精神病理分相关(F=8.655,P=0.007),回归系数为-29.240。叶酸×双歧杆菌交互项与认知功能无相关性(均P>0.05)。结论首发未用药SCZ患者中血清叶酸水平和双歧杆菌相对丰度下降,并且与其精神症状相关,提示菌群相对丰度和叶酸水平可作为精神症状的潜在客观评估指标。

Objective To explore the effects of gut microbiota and the serum level of folicacid on psychiatric symptoms in first-episode,drug-free schizophrenic(SCZ)patients.Methods A total of 100 first-episode,drug-free SCZ patients(SCZ group)from the First Affiliated Hospital of Zhengzhou University and 90 demographically matched healthy individuals(healthy control group)were enrolled.The serum level of folic acid was measured by the electrochemical luminescence method.Positive and Negative Syndrome Scale(PANSS)was used to assess the psychiatric symptoms and Matrics Consensus Cognitive Battery(MCCB)was used to evaluate cognitive function.Bacterial DNA was extracted from the fecal samples for high-through put sequencing of the 16S rRNA.The effects of gut microbiota and folic acid on the psychiatric symptoms and cognitive function in SCZ patients were explored.Results A total of 41 males and 59 females,with an age of(22.6±8.2)years were included in the patient group,and 32 males and 58 females with an age of(23.0±3.0)years were included in the healthy control group.The fasting folic acid level inserum of the SCZ group was lower than that of healthy control group[6.92(4.98,8.49)μg/L vs 8.93(7.13,13.37)μg/L,P<0.001].The relative abundance of genus Bifidobacterium[0.005(0.003,0.013)vs 0.014(0.004,0.031)]and genus Bacteroides[0.015(0.001,0.091)vs 0.083(0.029,0.193)]was lower in the SCZ group than that of the healthy control group(both P<0.001).In comparison with the healthy control group,scores of cognitive function in the seven domains were significantly lower in the SCZ group(all P<0.05).In the patient group,the serum level of folic acid was negatively related to the negative symptom score(r=-0.378,P<0.001),but had a positive correlation with the score of speed of processing(r=0.310,P=0.011).In the SCZ group,the relative abundance of the genus Bifidobacterium was positively correlated with the serum level of folic acid(r=0.374,P<0.001)and the score of speed of processing(r=0.330,P=0.003)respectively,but was negatively correlated with the general psychopathology score(r=-0.326,P=0.001).The results of multiple linear regression analysis showed that the interaction term between folic acid and genus Bifidobacteriumin in SCZ patients were correlated with the general psychopathology score,with a regression coefficient of-29.240(F=8.655,P=0.007).There was no statistical correlation between the aforementioned interaction term and cognitive function(both P>0.05).Conclusion In first-episode,drug-free SCZ patients,there were decreases in the serum folic acid level and the relative abundance of genus Bifidobacterium,which were related to the psychiatric symptoms,suggesting that these two substances can be used as potential objective indicators for evaluating psychiatric symptoms.