| Objectives1.Comparison of structural characteristics of intestinal microflora between first episode schizophrenics and healthy controls.2.Comparison of faecal short chain fatty acids between first episode schizophrenics and healthy controls.3.To analyze the relationship between intestinal microflora,fecal short chain fatty acids and mental symptoms in first episode schizophrenia,to explore the possible role of intestinal microflora and its metabolite short chain fatty acids in schizophrenia.Methods1.From December 2017 to December 2019,49 patients(case group),medical staff and 50 healthy volunteers(control group)were selected from the Department of psychiatry,the First Affiliated Hospital of Zhengzhou University.On the day of admission,all patients were asked about their medical history,physical examination and psychiatric examination,collected general clinical data and assessed with positive and negative symptom scale.2.The fresh morning stool was collected by sterile sealed collecting tube and stored in-80? refrigerator immediately.Analysis of the diversity and difference of intestinal microflora between the two groups by 16S rRNA gene high throughput sequencing;Gas chromatography-mass spectrometry was used to detect the content of short chain fatty acids in the feces of the two groups,and the correlation between intestinal microflora,fecal short chain fatty acids and mental symptoms was further analyzed.3.SPSS24.0 statistical soft ware was used to analyze the experimental data.Two independent samples t-test was used to test the normal distribution data of age,education level and alpha diversity index of two groups,and the results were expressed as mean ± standard deviation(x±s).The relative abundance of intestinal microflora at the level of phylum,class,family and genus showed a skew distribution,and Wilcoxon rank sum test was used for group comparison,and the results were expressed as median(upper quartile,lower quartile)[M(QL,Qu)].Gender and other categorical variables were analyzed by chi-square test or continuous correction chi-square test,and the percentage of the number of use cases in the result was expressed as[example(%)].Spearman rank correlation was used to analyze the correlation between relative abundance of intestinal microflora and SCFAs level,PANSS score,and Pearson correlation was used to analyze the correlation between SCFAs level and PANSS score p<0.05 showed that there was significant difference between the two sides.Results1.There was no significant difference in age,education,gender and smoking history between the two groups(ps>0.05).2.The results showed that the Shannon index of the case group(5.11±0.70)was lower than that of the control group(5.84±0.59),and the Simpson index of the case group(0.96±0.01)was higher than that of the control group(0.90±0.07),and the differences were statistically significant(ps<0.01).There was no significant differences between the two groups in Chao1 index and Ace index(ps>0.05).The results of Beta diversity analysis showed that there were significant differences in the composition of intestinal microflora between the two groups.3.The difference analysis of species composition showed that the relative abundance of Actinobacteria and low abundance of fusobacteria and phylum of soft wall in the case group were lower than those in the control group(ps<0.05).At the class level,The relative abundance of Bacilli,Erysipelotrichia and unidentified_Actinobacteria in the case group were lower than those in the control group(ps<0.05).At the family level,the relative abundances of Lachnospiraceae,Bacteroideae,Bifidobacteriaceae,Peptostreptococcaceae and low abundances Rikenellaceae in the case group were lower than those in the control group,and the relative abundances of Veillonellaceae and Prevotellaceae were higher than those in the control group(ps<0.05).At the genus level,the abundance of the Unidentified_Ruminococcaceae,Bifidobacterium,Blautia and Bacteroides in the case group were lower than those in the control group(ps<0.05).In addition,through the analysis of LDA Effect Size,we identified 12 markers with LDA score>4,among which Prevotellace,unidentified_Prevotellace,Negativicutes,Selenomonadales,Veillonella ceae were the dominant groups of schizophrenia,Lachnospiraceae,Blautia,Bacteroideae,Bacteroides,Pepsostretotococcaceae,Romboutsia,unidentified_Ruminocaceae are the dominant groups of the control group.4.The levels of total short chain fatty acids,acetic acid,isovaleric acid and hexanoic acid in the case group(4.80±1.87,4.00±1.83,0.07±0.03,0.04±0.01)ug/mL was higher than those of the control group(3.74±1.60,3.10±1.62,0.05±0.02,0.03±0.01)ug/mL,and the concentration of isobutyric acid(0.04±0.02)ug/mL was lower than that of the control group(0.05±0.02)ug/mL,and the differences are statistically significant(ps<0.05).5.The correlation analysis of intestinal microflora and short chain fatty acids with PANSS score showed that the relative abundance of Prevotellaceae was positively correlated with the positive symptom score(r=0.390,p=0.012),and the relative abundance of Lachnospiraceae was negatively correlated with the positive symptom score(r=-0.433;p<0.01).The total SCFAs and acetic acid levels in feces were negatively correlated with PANSS positive symptom scores(r=-0.463,p=0.001;r=-0.403,p=0.004).6.The correlation analysis between short chain fatty acids and intestinal microflora showed that the levels of total short chain fatty acids and acetic acids were positively correlated with the relative abundance of Lachnospiraceae(r=0.389,p=0.006;r=0.355±p=0.012)and the levels of propionic acid was positively correlated with the relative abundances of Negativicutes,Selenomonadales and Veillonellaceae(r=0.323,p=0.035;r=0.322,p=0.035;r=0.354,p=0.020),the levels of valeric acid was positively correlated with the relative abundances of Negativicutes,Selenomonadales and Veillonellaceae(r=0.354,p=0.012;r=0.331,p=0.020;r=0.318,p=0.026).Conclusions1.There are significant differences in the characteristics of intestinal microflora between the first episode schizophrenics and the healthy controls.12 bacteria such as Prevotellaceae,unidentifide_Prevotellaceae may be the biomakers of schizophrenia.2.The level of faecal short chain fatty acids in first episode schizophrenia has changed,the level of total short chain fatty acid,acetic acid,isovaleric acid and hexanoic acid in feces was higher than that in healthy people,and the level of isobutyric acid was lower than that in healthy people.3.The relative abundance of Lachnospiraceae was correlated with fecal acetic acid and total short chain fatty acids,and all of them were correlated with positive symptom score,suggesting that the changes of intestinal microflora and short chain fatty acids may be involved in the pathogenesis of schizophrenia. |
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