Research On The Diversity Of Skin Microbiota In Female Patients With Systemic Lupus Erythematosus

Background Systemic lupus erythematosus（SLE）is a kind of severe autoimmune diseases involving multiple organ systems with diverse clinical manifestations.SLE tends to occur in women of childbearing age.skin manifestations are common in SLE patients and occur in approximately 80% of patients during the course of SLE.Importantly,skin manifestations are the first symptom of SLE in up to 25% of cases.It is difficult to identify the skin manifestations of SLE patients,so it is easy to delay the diagnosis and treatment of SLE.Skin is the largest organ of the human body,with many beneficial,symbiotic,neutral,and potentially pathogenic microbes.Some studies suggest that compared with the skin of healthy people,the disorder of skin microbiota is related to several skin diseases and immune diseases.The alteration of skin microbial community might play an important role in autoimmune diseases.Although exposed to the external environment,the structure and function of skin microbiota are stable at each taxon level,and have site and individual specificity,which provides a basis for the exploration of skin microbiota in different disease states.ObjectivesTo identify the differences of skin microbiota between skin rash of female patients with SLE and control populations,to analyze changes of skin microbial diversity and composition of SLE patients with different clinical feature,to study the correlation between the significant different bacteria in the skin microbiota of SLE patients and clinical indicators,and to found the skin microbial specificity of SLE patients.MethodsA case-control design was used in this study.Skin samples from rash and non-rash sites of female patients with SLE,rash sites of rosacea patients and healthy controls were collected.16S rRNA sequencing was applied to detect skin microbiota.The diversity and structure of skin microbiota in SLE patients were identify.Wilcoxon rank sum test and linear discriminant effect size analysis were used to identify the differences of skin microbial community and function between SLE patients and controls.Differences of skin microbiota under different clinical symptoms were analyzed.Spearman correlation analysis was conducted to measure the correlation between different species of skin microbiota and laboratory indexes in SLE patients.ResultsA total of 80 skin samples were collected from rash and non-rash sites of female patients with SLE,rash sites of rosacea patients and healthy controls for microbiological detection.The microbial diversity and composition in skin rash of SLE patients were altered.Compared with the three control groups,Firmicutes,Bacilli,Bacteroidetes,Bacteroidales,Bacteroidia,Clostridia,Clostridiales,Pseudomonas,Moraxelaceae Prevotellaceae and others were enriched in skin rash of SLE.Based on the Kyoto Encyclopedia of genes and genomes database,it was found that the genetic information processing,replication and repair,translation,nucleotide metabolism,energy metabolism and ribosomal pathways of microbiome skin rash of SLE significantly increased,while the metabolic pathways of heterologous biodegradation and metabolism decreased.The abundance of Verrucomicrobiaceae and Aerococcaceae increased in the low activity group,while the abundance of Hyphomonaceae,Bacteroidaceae,Caulobacteraceae and Pseudomonasaceae increased in the high activity group.Caulobacteraceae had a positive correlation with systemic lupus erythematosus disease activity index-2K（SLEDAI-2K）（r=0.50,P=0.025）,and a negative correlation with complement 3（r=-0.58,P=0.007）;Aerococcaceae was negatively correlated with SLEDAI-2K（r=-0.52,P=0.020）and immunoglobulin G（r=-0.46,P=0.043）;Dechloromonas was negatively correlated with erythrocyte sedimentation rate（r=-0.58,P=0.007）and anti ds-DNA（r=-0.58,P=0.007）.Kingella was negatively correlated with SLEDAI（r=-0.49,P=0.027）,but positively correlated with immunoglobulin A（r=0.55,P=0.012）.ConclusionsThis study illustrates the alteration of microbial diversity and composition,and some metabolic functions of microbiota in SLE skin rash.Based on different skin microbiota,it may provide clues for further exploration of SLE diagnosis and treatment from a new perspective.This study has made a preliminary exploration on the skin microbiota of SLE patients.In the future,a larger sample size is needed to further explore the important functional role of skin microbiota in SLE.