Fecal Short-chain Fatty Acid Contents And Their Correlations With Th17 And Treg Levels In Patients With Systemic Lupus Erythematosus

BackgroundSystemic lupus erythematosus（SLE）is a chronic autoimmune disease with complex etiology.It mainly occurs in women of childbearing age,with sex ratio（male to female）is up to 1:9.Compared to people of other races,the prevalence and incidence of SLE are higher in Black,Asian and Hispanic populations.However,the causes of SLE remains unknown.Recent studies have shown that environmental factors played important roles in the occurrence and development of SLE,such as diet,infection,microorganisms and other factors.The microorganisms of human body,mainly include bacteria,fungi,archaea and viruses,constitute a complex micro-ecosystem.At present,a number of studies have shown that disordered gut microbiota in patients with SLE might be related to the occurrence and development of SLE.Changes of gut microbiota might affect its metabolites,leading to occurrence and development of disease.Moreover,studies found that some short-chain fatty acids（SCFAs）producing microbes（such as butyrate-producing microbes）in gut of SLE patients showed a downward trend.SCFAs were mainly produced by lactobacillus,bifidobacterium and other beneficial bacteria in the colon through digesting indigestible carbohydrates such as dietary fiber,resistant starch,oligosaccharides and other indigestible carbohydrates.SCFAs could promote the growth of beneficial bacteria in human body by reducing the p H value in colon environment,so as to improve the imbalance of gut microbiota.More than 70%of immune cells in the human body inhabit gut.But instead of stagnating in the gut,these cells could move to various parts of the body to play a role.T helper cell 17（Th17）and regulatory T cells（Treg）are effector T cells activated by naive CD4⁺T cells.Researchers found that the imbalance of Th17 and Treg cells might induce or aggravate the symptom of SLE.Previous studies also showed that SCFAs might affect the balance of Th17 and Treg cells.However,no studies have demonstrated correlations between SCFAs in the gut of SLE patients,Th17 cells,Treg cells and relative cytokines.ObjectiveTo describe differences of SCFAs content between SLE patients and healthy controls（HCs）,to explore possible impacts of different disease characteristics of SLE patients on SCFAs in stool,to study roles of Th17 cells,Treg cells and relative cytokines in SLE,and to clarify correlations between SCFAs in the gut of SLE patients,Th17 cells,Treg cells and relative cytokines.MethodsGas chromatography-mass spectrometer was used to determine contents of acetic acid,propionic acid,butyric acid,valeric acid,isovaleric acid and isobutyric acid in feces of SLE patients and HCs.Flow cytometry was used to determine contents of Th17 and Treg cells.Cytometric bead array and enzyme linked immunosorbent assay were applied to determine contents of Intertleukin-10（IL-10）,IL-17A,IL-21 and IL-22 in serum of SLE patients and HCs.Mann-Whitney U test was used to compare contents of SCFAs,Th17 cells,Treg cells and related cytokines among different groups.Spearman correlation analysis was used to explore correlations of SCFAs,Th17 cells,Treg cells and related cytokines in SLE patients and HCs.Results1.Compared with HCs,there are differences in the SCFAs in stool of SLE patients,so as in Th17,Treg cells and relative cytokines.Compared with HCs,butyric acid in SLE patients was decreased,while isobutyric acid and isovaleric acid were increased,all with significant differences.The proportion of Th17 and Treg cells in PBMCs of SLE patients showed upward trends,but with no statistic difference.Besides,the contents of IL-10 and IL-17A in the serum of SLE patients were increased,and the differences were statistically significant.2.The contents of some SCFAs in SLE patients’stool were correlated with Th17,Treg cells and relative cytokines.The contents of isovaleric acid,isobutyric acid and valeric acid were negatively correlated with Th17 cells and the ratio of Th17/Treg.There was a positive correlation between Treg and Th17 cells.The systemic lupus erythematosus disease activity index was positively correlated with the ratio of Th17/Treg.Anti-double-stranded DNA antibody was positively correlated with IL-10 and negatively correlated with IL-21 and IL-22.3.Compared to SLE patients without nephritis,the content of butyric acid in stool of SLE patients with nephritis was decreased with a significant difference.In SLE patients with nephritis,we found positive correlation between isovaleric acid and IL-22.There was a positive correlation between isobutyric acid and IL-22.The acetate was negatively correlated with IL-17A.And IL-21 was positive correlated with the content of IL-17A with a significant difference.ConclusionsCompared with HCs,there are differences in SCFAs in stool of SLE patients,as well as Th17 and Treg-related cytokines.The contents of some SCFAs in stool of SLE patients were correlated with Th17,Treg cells and relative cytokines.Compared with SLE patients without nephritis,patients with nephritis had lower fecal butyric content.