Alterations Of The Human Oral Microbiome And Development Of A Prognostic Model In Systemic Lupus Erythematosus

Systemic lupus erythematosus(SLE)is the prototype of autoimmune disease,which is characterized by a wide variety of auto-antibodies production and clinical manifestations.The disease is more common in females of childbearing age,the incidence in female is about 9-11 times higher than that in male.The pathogenesis of SLE is still poorly understood and multiple factors may involve in the development of disease,including genetic,epigenetic,immunoregulatory,ethnic,hormonal,and environmental factors.Recent years,the overall survival of patients with SLE has greatly improved with the advances in diagnosis and management.The human microecosystem has an important role in the maintenance of human health and disease pathogenesis.In disease state,the human oral microecology may become disorganized,and each disease has its own unique oral microbial alterations.In addition,the microbiome is closely related to disease recovery.Nevertheless,the characteristics of oral microbiome in SLE have been rarely reported.Furthermore,patients with SLE may sometimes admit to the intensive care unit(ICU)due to lifethreatening conditions,and the outcome is still poor.Although there are numerous reports regarding the clinical features and outcome of patients with SLE admitted to the ICU.However,the number of patients was relatively small in the majority of studies,and a scoring system was not established.To address these issues,this study intends to investigate the alterations of oral microbiome in SLE and the clinical features of SLE admitted to the ICU from the following two aspects.Part 1:Alterations of the human oral microbiome in SLE.Part 2:Development of a prognostic model of SLE.Part 1 Alterations of the human oral microbiome in systemic lupus erythematosusObjectiveTo characterize the oral microbiome profiles in patients with SLE,evaluate the potential of the microbiome as a non-invasive biomarker for SLE.MethodsWe sequenced and analyzed 420 tongue coating samples.According to the random number table,samples were divided into two mutually exclusively cohorts named derivation(n=100)and validation(n=40).We characterized the oral microbiome,constructed microbial classifiers in the derivation cohort and verified their diagnostic potential in the validation cohort.ResultsCompared with healthy controls(n=200),oral microbial diversity is increased in SLE(n=100),and the microbial community is remarkably distinguished from health control.Genera Prevotella and Veillonellaare are enriched,while Streptococcus and Porphyromonas are reduced in SLE.Twenty-seven predicted microbial functions including ansamycins,arginine and ornithine metabolisms increase,while 34 functions including aminobenzoate and unsaturated fatty acid metabolisms decrease in SLE.Notably,two optimal microbial markers are identified by the random forest model.The area under the curve value of the probability of disease index reaches 0.9166 in the derivation cohort and 0.8422 in the validation cohort.Moreover,Abiotrophia and Lactobacillales are increased with SLE disease activity progression,while phyllobacterium and unclassified micrococcaceae are decreased.Conclusions1.The oral microbial diversity is increased in SLE,and the microbial community is distinguished from health control.2.The microbial classifiers may have great potential as a non-invasive diagnostic biomarker for SLE.Part 2 Development of a prognostic model in systemic lupus erythematosusObjectiveTo explore the clinical features of patients with SLE admitted to the ICU,identify prognostic factors,and develop and evaluate a prognostic model to predict in-ICU mortality of patients with SLE.MethodsThis was a single center retrospective study.A total of 480 SLE patients with 505 ICU admissions from October 2010 to October 2019 were screened,and 391 patients were enrolled.The clinical feature and outcomes of the patients were analyzed.According to the random number table,patients were divided into two mutually exclusively cohorts named derivation(n=293)and validation(n=98).Prognostic factors were identified by a Cox model with Markov Chain Monte Carlo simulation and evaluated by latent analysis.The risk score was developed based on the derivation cohort and evaluated by the validation cohort.ResultsAmong the 391 patients,348 patients were females.The median age of patients was 34 years,and the median course of SLE was six months.The median APACHEII and SLEDAI were 17 and 10,respectively.The average in-ICU mortality was 53.4%.A total of 186 patients were admitted to the ICU due to infection.Pneumonia(320/391,81.8%)was the most common clinical manifestation followed by renal disease(246/391,62.9%).Nine prognostic factors including age,white blood cell count,alanine transaminase,uric acid,intracranial infection,shock,intracranial hemorrhage,respiratory failure,and calcineurin inhibitors usage were identified,and a model was developed.The model had C statistic of 0.912(95%CI,0.889-0.948)and 0.807(95%CI 0.703-0.889),with predictive range of 5.2%-98.3%and 6.3%-94.7%for the derivation and validation cohorts,respectively.Based on distribution of the risk score,25.3%,49.5%,and 25.2%of patients were stratified into the high,average,and lowrisk groups,with corresponding in-ICU mortality of 0.937,0.593,and 0.118,respectively.Conclusions1.The mortality rate of patients with SLE admitted to the ICU remains high.2.The prognostic model can better predict the outcome of patients with SLE admitted to the ICU,and help clinicians stratify patients according to their risk of death.