Research On The Diversity Of Intestinal Fungi In Patients With Systemic Lupus Erythematosus

BackgroundSystemic lupus erythematosus(SLE)is caused by abnormal autoimmune reactions of human body.SLE is systematic and has clinical heterogeneity.Most SLE patients(women of childbearing age)involve important organs and tissues such as the brain,kidneys,and blood during the progression of the disease.The incidence is 20-150 cases per 100,000 people,and with the improvement of SLE diagnostic ability and survival rate,the incidence rate shows an increasing trend.Although the proportion of intestinal fungi is small,it plays an important role in human health.Existing research suggests that intestinal fungal disorders are associated with autoimmune diseases compared to the healthy people.Changes in fungal communities may have an important impact on the progression of autoimmune diseases.However,the characteristic of intestinal fungi in SLE patients are still unclear.ObjectiveThe aim of this study is to explore the diversity and composition of intestinal fungal community between SLE patients and healthy controls(HCs);The characteristics of intestinal fungal in SLE patients with different disease activity and clinical subtypes were analyzed;To explore the correlation between differential fungi and laboratory indicators.MethodsFrom June 2021 to September 2022,a total of 50 newly diagnosed SLE cases without drug treatment were collected from the Rheumatology and Immunology Department of Anhui Provincial Hospital and the First Affiliated Hospital of Anhui Medical University.At the same time,50 HCs matched with age,body mass index and diet of SLE were recruited as the control from the physical examination center of Anhui Medical University and the First Affiliated Hospital of Anhui Medical University.Results1.Compared with HCs,the diversity of intestinal fungi in SLE patients is decreased.There were significant differences in fungi composition between the SLE group and the HCs group.We observed that the Ascomycota,Geminibasidiomycetes,Saccharomycetes,Cystobasidiomycetes,Geminibasidiales,Saccharomycetales,Cystobasidiomycetes＿ord＿I ncertae＿sedis,Saccharomycetales＿fam＿Incertae＿sedis,Geminibasidiaceae,Lentitheciace ae,Symmetrosporaceae,Candida,Geminibasidium,Neocamarosporium,Conlarium,Acrop hilophora,Dimorphosporicola,Candida albicans,Symmetrospora oryzicola,Conlarium aquaticum,Dimerphosporicola tragani,Apiotrichum laibachii,Canariomyces arenarius,Acrophilophora levis were enriched in SLE patients.Basidiomycota,Boeremia,Ustilago,Cercophora,Mortierella stylospora,Cutaneochosporon moniliform and Acremonium exuviarum were enriched in HCs.At the same time,there were significant differences in Alpha and Beta diversity between SLE and HCs groups.2.According to the ITS sequencing results,the composition of fungal microorganisms among SLE low disease activity group(SLE-L),middle disease activity group(SLE-M)and high disease activity group(SLE-H)has statistical differences.Alpha diversity and Beta diversity analysis showed that there was no significant difference between the three groups.LEf Se analysis showed that 46 fungal species at different taxonomic levels had differences among the three groups.3.There were differences in fungal species composition between non-lupus nephritis group(NLN)and lupus nephritis group(LN),but there was no significant difference in alpha diversity and beta diversity between the two groups.LEf Se analysis showed that the relative abundance of 10 species at different taxonomic levels was different between the two groups.The abundances of Conioscyphales,Torulaceae,Conioscyphaceae,Sporocadaceae,Triplosphaeria,Limonomies,Conioscypha,Xenomyrothecium,Adisciso in LN group were increased,and the abundances of Xylariales＿fam＿Incertae＿sedis and Phialemoniopsis were increased in NLN group.4.The correlation analysis between differential fungi and clinical indicators showed that Conlarium and Conlarium aquaticum enriched in SLE patients were negatively correlated with Ig A(r=-0.327,P=0.027),and Canariomyces arenarius was positively correlated with CRP(r=0.289,P=0.044).Corticiales,Corticiaceae and Limonomyces enriched in SLE-H group were positively correlated with Ig G(r=0.320,P=0.034).The Sporocadaceae(r=0.295,P=0.046)and Limonomyces(r=0.322,P=0.029)enriched in the LN group were positively correlated with Ig G.There was a negative correlation between Phialemoniopsis and ESR in the NLN group(r=-0.304,P=0.038).ConclusionThere are significant differences between the composition and diversity of intestinal fungal microorganisms in SLE patients and HCs.This discovery may provide a theoretical basis for exploring the role of fungi in SLE.In addition,the comparison of different disease activity in SLE patients find that the species composition of fungi among SLE-L,SLE-M and SLE-H is different.The species composition of fungi between NLN group and LN group is also different.The correlation analysis between fungi species and clinical serological indicators of SLE also suggests that fungi are related to the disease progression of SLE.The above evidences reveal that the disease development of SLE may be related to the characteristic changes of intestinal fungi.