High-throughput Sequencing And Metabolomic Analyses Gut Microbiota In Systemic Sclerosis Patients

Objective: The aim of this study was to compare and analyze the composition of microbiota and metabolites in the excrement of patients with systemic sclerosis(SSc)and healthy controls,to explore the potential relationship between microbiota and SSc,providing a new method for the treatment of SSc.Methods: A total of 12 consecutive SSc patients and 11 sex-and agematched healthy controls were enrolled in this study between December2020 and February 2022 in Xiangya Third Hospital of Central South University.Fecal samples were collected from all study subjects,16 S r RNA high-throughput sequencing technology was used to analyze the flora structure of SSc group and control group,and the diversity and difference of microbiota between SSc group and control group were analyzed.The metabolites expression was analyzed by using non-targeted ultra performance liquid chromatography technique,and the differential metabolites of each group were screened for association analysis of differential microbiota and differential metabolites.Results:(1)Our results showed significant differences in microbiota composition in SSc patients compared to controls.Individual differences in intestinal flora were greater in SSc patients.In the microbiome analysis,butyrate-producing genera such as Faecalibacterium,Ruminococcus,Roseburia,and Lachnospira decreased in abundance,while Streptococcus,Actinomyces,and Lactobacillus were the differential genera for SSc.Streptococcus,Dorea,Ruminococcus and Collinsella were also associated with m RSS scores and Raynaud’s phenomenon.(2)In the metabolomic analysis,there was a significant difference in metabolites expression levels between the two groups.The metabolic pathways significantly affected in SSc includes lysine degradation,tyrosine metabolism and c AMP signaling pathway.Among them,the major differential metabolites such as Succinate,adenosine,5-aminovaleric acid,L-pipecolic acid and N-methyltyramine were down-regulated in SSc.(3)In association analysis,Actinomyces were negatively associated with Succinate,L-pipecolic acid and adenosine,and Streptococcus were negatively associated with L-pipecolic acid,adenosine and 5-aminovaleric acid.Dialister was positively correlated with Succinate,adenosine and 5-aminovaleric acid,and Faecalibacterium was positively correlated with Succinate and L-pipecolic acid.Conclusion: Patients with SSc have significant dysbiosis and metabolite changes,and the close correlation between differential microbiota and clinical symptoms and fecal metabolites provides new clues for the diagnosis and treatment of SSc.