Correlation Analysis Of Intestinal Flora And Short-chain Fatty Acid Characteristics In Inflammation-associated Depression

Objective:Depression is a psychiatric disorder that has a serious impact on human physical and mental health.Previous studies have shown that inflammation-associated depression is a subtype of drug-resistant depression that is associated with specific symptoms and biological abnormalities.The gut microbiota may be a source of low-grade inflammation.Therefore,this study analyzed the gut flora and short chain fatty acid levels in patients with inflammation-associated depression to explore the relationship between them,aiming to provide a theoretical basis for the early identification,prevention and prognosis of inflammation-associated depression.Methods:1.Eighty-five patients with depressive disorders who were not on antidepressant treatment and 85 healthy subjects were recruited,and general demographic data of the subjects were collected.We assessed their anxiety and depression levels using the Hamilton Anxiety Inventory(HAMA)and the 17-item Hamilton Depression Inventory(HAMD-17)respectively.We used 16 S r RNA gene sequencing to detect the sequences of the intestinal flora of the two groups.The two groups of intestinal flora were compared in terms of diversity and species composition,and the differential strains of the two groups were identified.The levels of short-chain fatty acids and inflammatory factors in plasma were measured by gas chromatography-mass spectrometry(GC-MS)and enzyme-linked immunosorbent assay(ELISA)respectively.We compared the differences in intestinal flora,short-chain fatty acids,clinical symptoms and inflammatory factors between the two groups of subjects,and analyzed the correlation between the above indicators.2.Depressed patients(n=85)were divided into inflammation-associated depression group(n=42)and non-inflammation-associated depression group(n=43)according to peripheral blood hs-CRP concentration.There were 85 healthy subjects.The differences between the three groups of subjects in terms of intestinal flora,short-chain fatty acids,clinical symptoms and inflammatory factors were compared and correlations between these indicators were performed.3.Twenty patients were randomly selected from the inflammation-associated depression group(n=42)and 20 subjects were randomly selected from the healthy control group(n=85).Metagenomic sequencing was used to identify specific strains closely associated with inflammation-associated depression and their functions at the species level.Results:1.There were no significant differences in age,gender and body mass index(BMI)between the depression group and the healthy controls(P > 0.05).The depression group had significantly fewer years of education than HCs(P<0.001).The total scores of HAMD-17 and HAMA,and the 5-factor score of the HAMD-17 were higher in the depression group than in the healthy controls(P < 0.001).The level of hs-CRP in the depression group was significantly higher than that in the healthy control group(P <0.001),while the levels of propionic acid and butyric acid were significantly lower than those in the healthy control group(P < 0.05).There were differences in alpha diversity and beta diversity between the two groups.LEf Se analysis identified 21 characteristic species that were significantly different between the two groups(LDA > 2).Correlation analysis revealed positive correlations between hs-CRP level and HAMD-17 scores,four factor scores of HAMD-17(anxiety/somatization,cognitive disturbance,sluggish,somnipathy),HAMA scores,concentration of acetic acid,but negative correlations with Clostridium(P < 0.05).2.There were no significant differences in age,gender and BMI among the inflammation-associated depression group,non-inflammation-associated depression group and healthy control group(P>0.05).Subjects in the three groups differed in years of education,total score of HAMD-17,5-factor score of HAMD-17 and total score of HAMA(P < 0.05).IL-6,propionic acid and butyric acid concentrations differed among the three groups(P < 0.05).There were no significant differences between inflammation-associated depression group and non-inflammation-associated depression group in general demographic data,clinical symptoms,short-chain fatty acid and inflammatory factors except hs-CRP(P >0.05).The relative abundance of the pro-inflammatory bacteria Bacteroidaceae and Bacteroides were found to be significantly higher in patients with inflammation-associated depression than in non-inflammation-associated depression and healthy controls by LEf Se analysis,whereas the relative abundances of anti-inflammatory bacteria Clostridiaceae,Faecalibacterium and Clostridium were lower.Correlation analysis revealed that the relative abundance of Clostridiaceae and Clostridium were negatively correlated with scores of anxiety/somatization,cognitive disturbance,sluggish and somnipathy.3.Stool samples were determined by shotgun metagenomic sequencing.We performed LEf Se analysis and found that 43 species were reduced in relative abundance and 9 species were enriched in the inflammation-associated depression group.Mogibacterium diversum enriched in the inflammation-associated depression group was positively correlated with hs-CRP and HAMD-17 total score.In addition,we found that the expression of K00244(fumarate reductase A)was significantly reduced in the inflammation-associated depression group.After annotating K00244 into KEGG Pathway Maps,abnormal butyrate metabolism(map00650)was found.Conclusion:1.Patients with depression had lower propionic acid and butyric acid levels,higher hs-CRP levels in peripheral blood,and changed in the composition of the intestinal flora compared to the healthy population.2.The relative abundance of pro-inflammatory bacteria Bacteroides were higher in patients with inflammation-associated depression,while the relative abundance of anti-inflammatory bacteria Clostridium and Faecalibacterium,which produce short-chain fatty acids,was lower.3.Propionic acid and butyric acid levels in peripheral blood of patients with inflammation-associated depression were decreased.The relative abundance of Bacteroides was negatively correlated with the concentration of propionic acid and butyric acid,and positively correlated with the severity of depressive symptoms.4.The expression of K00244(fumarate reductase A)was significantly reduced in patients with inflammation-associated depression,and butyrate metabolism(map00650)was abnormal.