Study Of The Correlation Between Gut Microbiota And Lipid Metabolism In First-episode Schizophrenic

Objectives1.To observe the difference in the relative abundance of gut microbiota and serum lipid between first-episode schizophrenics and healthy control.2.To observe the dynamical changes in gut microbiota,lipid metabolism and the scores of psychiatric symptoms after treatment with antipsychotic drugs.3.To analyze the correlation between the gut microbiota,serum lipid and psychiatric symptoms in first-episode schizophrenia,and further investigate the influence of gut microbiota on the imbalance of lipid metabolism caused by antipsychotic drugs.Methods1.Eighty and seven drug-free first-episode schizophrenic patients were recruited to the psychiatric department of the First Affiliated Hospital of Zhengzhou University from April 2018 to April 2020.Ninety demographically matched healthy volunteers in the Zhengzhou area were recruited through advertisements.All participants were ascertained through the sociodemographic characteristics interview,physical examination,and laboratory tests.All enrolled subjects were collected for fasting venous blood and the fecal samples in the early morning after enrollment.Height and weight were measured to calculated body mass index(BMI).The Positive and Negative Syndrome Scale(PANSS)was used to assess psychiatric symptoms in patients.The patient group was followed up during medication treatment for 12 weeks and 24 weeks.2.Serum levels of triglyceride(TG),total cholesterol(TCHO),high-density lipoprotein(HDL)and low-density lipoprotein(LDL)were measured by enzymatic colorimetric assay.Serum level of glucose(GLU)was measured by glucose oxidase method.3.The bacterial DNA was extracted by QIAamp Fast DNA Stool Mini Kit according to the manufacturer’s instructions.DNA concentrations were tested by ultraviolet spectrophotometer.The absolute copies of bacteria were quantified by quantitative polymerase chain reaction(PCR):according to the 16S rRNA gene sequences,designing the specific primers by targeting the V4 region,constructing standard plasmid.Sequences with more than 97%identity are clustered into Operational Taxonomic Units(OTUs).And species annotation based on the SSUrRNA database.4.The data were analyzed using SPSS version 25.0.The normal distributed data were described in the form of mean and standard deviation(X±S).Two independent-sample t test were used to compare the measurement data between groups.The correlation test uses Pearson correlation analysis.The non-normal distributed data were described in the median(lower quartile,upper quartile)[M(QL,QU)].The measurement data between groups were compared using the Mann-Whitney U test.Spearman rank correlation was used to analyze the correlation.Categorical variables were tested by the chi-square test.The changes of biological indicators in the patient group were analyzed using a mixed effect model.And P<0.05(two-tailed)was considered statistically significant.Results1.A total of 87 schizophrenes were enrolled in the patient group and a total of 90 volunteers were enrolled in the control group.There were no significant differences in gender,age,education,smoking between the two groups(P>0.05).2.The serum levels of TCHO,TG,HDL,LDL and BMI between patients and controls were no significant differences(all P>0.05).The serum level of GLU in patients was higher than that of controls(P=0.002).3.The results of Alpha diversity analysis suggested that the Shannon index of the patient group was lower than that of the control group,and the Simpson index of the patient group was higher than that of the control group,and the differences were statistically significant(all P<0.05).There were no significant differences between the two groups in Chao1 index and Ace index(all P>0.05).The result of the Beta diversity analysis showed that there was a significant difference in the composition of gut microbiota between the patient group and the control group(P<0.001).The relative abundance of family Ruminococcaceae,family Lachnospiraceae and family Bacteroidaceae occupied the dominant position in the gut microbiota structure.In the family level of gut microbiota,the relative abundance of family Bacteroidaceae,Bifidobacteriaceae,Rikenellaceae,Peptostreptococcaceae,Lactobacillaceae,Streptococcaceae and Pasteurellaceae in the patient group was lower than that of the control group(all P<0.05),and there was no significant difference in the relative abundance of family Enterobacteriaceae(P>0.05).4.After 24 weeks of treatment,serum levels of TCHO,TG,LDL and BMI in the patient group with the antipsychotic drug risperidone increased compared with those indexes of the baseline period(all P<0.05);Serum levels of HDL and GLU were not a significant difference in the two periods(all P>0.05).After 12 weeks of risperidone treatment,serum levels of TCHO,TG,LDL and BMI in the patient group were higher than those of the baseline period(all P<0.05),and levels of HDL and GLU were no significant difference in the two periods(all P>0.05).There was no significant difference in serum glycolipid indexes between the 12th week and the 24th week(all P>0.05).After 24 weeks of treatment,the Shannon index(P=0.357)and Simpson index(P=0.290)were not significantly different from those of the baseline period(both P>0.05).There was no significant statistical difference in the change of the Beta diversity index(P>0.05).The relative abundance of family Bifidobacteriaceae in the patient group decreased in 24 weeks compared with the baseline period(P<0.001);the relative abundance of 12 weeks decreased compared with the baseline period(P<0.001);the relative abundance between 12 weeks and 24 weeks had no difference statistical significance(all P>0.05).The relative abundance of family Streptococcaceae in the baseline period was not statistically different from that of 24 weeks(P>0.05);the relative abundance of 12 weeks was lower than that of the baseline period(P=0.034);the relative abundance of 24 weeks was higher than that of 12 weeks(P=0.040).The relative abundance of family Lactobacillaceae in the baseline period was not statistically different from that of 24 weeks(P>0.05);the relative abundance of 12 weeks was lower than that of the baseline period(P=0.012);the relative abundance between 12 weeks and 24 weeks was no significant difference(P>0.05).After 12 weeks and 24 weeks treatment with RIS,the positive symptom scores,the negative symptom scores,the general pathological symptom scores and total scales in PANSS of the patient group were significantly decreased compared with the baseline period(all P<0.05).Among the 60 patients who completed the 24-week follow-up,16 patients(26.7%)were clinically cured,29 patients(48.3%)were significantly improved,and 15 patients(25.0%)were effective.5.In the patient group,there was no correlation between serum lipids and gut microbiota(all P>0.05).The change of family Streptococcaceae was negatively correlated with the change of TCHO levels(r=-0.319,P=0.021)after 12-week treatment;the change of family Bifidobacteriaceae was negatively associated with the change of TG levels(r=-0.326,P=0.018)after 24-week treatment.In the patient group,the relative abundance of family Rikenellaceae family at baseline was negatively associated with the general pathological symptoms of PANSS(r=-0.410,P<0.001)and the total score(r=-0.334,P=0.002)respectively.After 12-week treatment^the change of family Lactobacillaceae was negatively correlated with the change of positive symptom score(r=-0.319,P=0.021).After 24-week treatment,the change of family Bifidobacteriaceae was negatively associated with the change of positive symptoms(r=-0.415,P=0.002).The multiple regression analysis showed that the relative abundance of family Bifidobacteriaceae was negatively correlated with positive symptoms and the level of TCHO was positively correlated with positive symptoms in the case group at 24 weeks,and the standardized regression coefficients were-0.316 and 0.272,respectively.The equation was statistically significant(F=5.195,P=0.009).Conclusions1.In the first-episode,drug-free schizophrenic patients,the diversity and relative abundance of gut microbiota changed,and there was no significant difference in lipids compared with the control groups,suggesting the imbalance of gut microbiota may play a potential role in the development of schizophrenia.2.Single antipsychotic drug risperidone induced structural changes of gut microbiota,abnormal metabolism of serum lipids,and improvement of efficacy scores.3.Gut microbiota were correlated with changes in serum lipid levels,and the correlation between lipid TCHO and the relative abundance of family Bifidobacteriaceae may potentially affect the changes in efficacy scores,suggesting that the gut microbiota may be a study of antipsychotic drug-induced metabolic disorders new direction.