The Research On The Characteristic And Interaction Of Gut Microbiota And Short-chain Fatty Acids In Depressive Disorder

Objective:Depressive disorder is a common mental illness that seriously affects the physical and mental health of patients.In the past decade,several studies have shown that patients with depressive disorders have gut microbiota disturbances and may affect depressive symptoms through gut microbiota metabolites such as short-chain fatty acids,but the relationship is still unclear.The primary goals of this study are to further understand the gut microbiota characteristics of individuals with severe depressive illness and to investigate the association between various bacterial genera and short-chain fatty acids.Second,to investigate the antidepressant properties of the primary short-chain fatty acid constituents and further examine the variations in gut microbiota between groups in order to offer fresh perspectives on the treatment of depression.Methods:The experiment was divided into two parts: the clinical component examined the association between the gut microbiota and short-chain fatty acids characteristics of depressive disorder using clinical data.Animal component: to investigate its anti-depressive impact and examine the alterations in the gut microbiota,short-chain fatty acid intervention was conducted on a CUMS rat model.Clinical component: this study included 25 healthy controls and 24 patients with major depressive disorders in total.The 24-item Hamilton Depression Scale(HAMD-24)was used to gauge the severity of the depression.The gut microbiota of the two groups was discovered using the 16 S r RNA sequencing method,and QIIME2 software was used to examine the diversity and various bacteria in the gut microbiota.Gas chromatography-mass spectrometry(GC-MS)was used to measure the participants’ plasma short-chain fatty acid concentration.The differences between the two groups were analyzed,and a correlation analysis was done between the various bacteria,the HAMD-24 score,and the short-chain fatty acid content.Animal component 76 male SD rats were randomly assigned to one of six groups:control(Control),chronic unpredictable stress model(CUMS),sodium acetate intervention(Acetate),sodium propionate intervention(Propionate),sodium butyrate intervention(Butyrate),and SCFAs intervention(SCFAs).There was a 28-day molding and intervention period.Behavioral assessments such as the forced swimming test,open field test,and sugar preference test were used to compare group differences in behavior and the effects of antidepressants.Cecal fecal samples from each group were taken in order to examine the variations in gut microbiota.Results:Clinical component: gut microbiota analysis: Alpha diversity: Chao1 index(P=0.021),Faith’s PD index(P=0.013),Good’s coverage index(P=0.008),Shannon index(P=0.002),Simpson index and Pielou’s Evenness index(P< 0.001)of MDD group were significantly lower than those of HC group;Beta diversity index: there were significant differences in Beta diversity between MDD group and HC group.Different gut microbiota:at the genus level,the abundance of bacteria related to short-chain fatty acid production in the HC group was significantly higher than that in the MDD group,such as Roseburia,Faecalibacterium,Ruminococcus,Dialister,Phascolarctobacterium,Prevotella,Lachnospira.Short-chain fatty acid analysis: the acetic acid(P < 0.001),propionic acid(P<0.001),isobutyric acid(P< 0.001),butyric acid(P< 0.001),isovaleric acid(P < 0.001),valeric acid(P < 0.001),caproic acid(P < 0.001)levels in MDD group were significantly lower than those in HC group.Correlation analysis: there was a significant negative correlation between the HAMD-24 scores and the scores of Roseburia(r=-0.711,P < 0.001)and Phascolarctobacterium(r=-0.596,P < 0.001).The HAMD-24 scores were negatively correlated with acetic acid(r=0.583,P < 0.001)and propionic acid(r=0.530,P < 0.001),isobutyric acid(r=0.393,P=0.006),butyric acid(r=0.378,P=0.008),isovaleric acid(r=0.390,P=0.006)and caproic acid(r=0.463,P=0.001)were positively correlated.Phascolarctobacterium and short-chain fatty acids included acetic acid(r=0.654,P< 0.001),propionic acid(r=0.450,P=0.001),isobutyric acid(r=0.405,P=0.004),butyric acid(r=0.303,P=0.036),isovaleric acid(r=0.411,P=0.004)and caproic acid(r=0.499,P < 0.001)were positively correlated.For the animal component: behavioral test: the sugar preference test: compared with the Control group,the sugar preference coefficient of the CUMS group decreased significantly(P=0.001);compared with CUMS group,sugar preference coefficient of Butyrate group(P < 0.001)and SCFAs group(P < 0.001)were significantly increased.Open field test: in terms of total distance,the total distance of CUMS group(P=0.034),Acetate group(P=0.021),and SCFAs group(P=0.033)was significantly different from that of Control group,indicating that CUMS group showed significant depression-like behavior.The sodium butyrate and short-chain fatty acids reversed depression-like behavior in this dimension;Forced swimming test: compared with CUMS group,the immobility time of Control group(P=0.001),Butyrate group(P < 0.001),and SCFAs group(P< 0.001)was significantly reduced,indicating that depressive like behavior is increasing in CUMS group.However,intervention of sodium butyrate and short-chain fatty acids can reverse this behavior.Gut microbiota analysis: there was no significant difference in Alpha diversity among the six groups;Beta Diversity: compared with Control group,significant differences were found among CUMS group(P=0.001),Acetate group(P=0.016),Propionate group(P=0.001),Butyrate group(P=0.001)and SCFAs group(P=0.001).The intervention did not significantly change the diversity of gut microbiota.Different gut microbiota: Streptococcus enriched after sodium acetate intervention;after sodium propionate intervention,Bifidobacterium was enriched Propionate group,Alteromonadales was enriched in Butyrate group,and Collinsella was enriched in SCFAs group.Conclusion:In clinical studies,gut microbiota of patients with major depressive disorder showed significant dysregulation and decreased levels of short-chain fatty acids.Roseburia and Phascolarctobacterium were significantly correlated with HAMD-24 scores and short-chain fatty acids.In animal studies,the sodium butyrate and short-chain fatty acids can significantly improve depressed-like behavior and regulate gut microbiota composition in rats.