Abstract

BackgroundGastrointestinal microbiota, particularly dysbiosis of gut microbiota composition have been correlated with the progression of autoimmune disorders, such as undifferentiated spondyloarthritis (USPA).ObjectivesThis study aimed to identify the changed gut microbiota and its relationship with lymphocyte subsets and cytokines in USPA Patients.MethodsA total of 210 participants were recruited in this study, comprising 105 USPA patients and 105 age and sex-matched healthy controls (HCs). Microbial genome was extracted from approximately 250mg fresh fecal samples from all participants using QIAamp PowerFecal DNA Kit (Qiagen). The V3-V4 variable regions of bacterial 16S rRNA genes were sequenced with the Illumina Miseq PE300 system. QIIME2 was used to process representative sequence clusters with a similarity cutoff of 100% (ASVs)1. Microbial diversity was estimated by the alpha diversity (observed, chao1, ACE, shannon, simpson, and ivsimpson) and beta diversity (bray distance). Biomarker species were identified based on STEMP between USPA and HC group. Correlations were analyzed with the Spearman rank correlation test.ResultsThe alpha-diversity indices have no significant different between two groups (P >0.05, Figure 1A). Gut microbial community structure differed between USPA and HC, as revealed by ASV Bray–Curtis distances (P <0.05, Figure 1B). As for composition of gut microbiota, there were the increased levels of Escherichia_Shigella, Flavonifractor, Hungatella in the USPA group, and Lachnospirales, Roseburia, and Lachnospiraceae in HCs (Figure 1C). The relative abundance of Lachnospiraceae_UCG_001 and Enterobacter was negatively correlated with the absolute numbers of Th17 (P<0.05). Bifidobacterium was positively correlated with the absolute number of Th1 and Tregs (P<0.01, Figure 1D). The relative abundance of Fusobacterium, Incertae_Sedis, and Colidextribacter were negatively correlated with the absolute numbers of Il-10, IL-4, and IL-2 (P<0.05). Prevotella and Enterobacter were positively correlated with the absolute number of IL-6 and IL-4 respectively (P<0.05, Figure 1E). Bifidobacterium and Bilophila were neagtively correlated with the absolute number of NK cell (P<0.05, Figure 1F).Figure 1.(A) Comparison of alpha-diversity indexs between HC and USPA groups was shown using boxplot. (B) β diversity of the gut microbiome in USPA patients and HCs. Principal coordinate analysis plot generated from the bray distance analyse. (C) STEMP was used to detect difference in Flora according to USPA and HC. (D-F) Relationship between gut microbiota, and Lymphocyte subsets as well as cytokines. *P<0.05, **P<0.01.ConclusionGut dysbiosis in USPA patients mainly characterized by reduced the diversity and impaired abundance of the intestinal flora, which was closely related to the disturbance of lymphocyte subpopulations and cytokines.

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