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Analysis Of Intestinal Flora And Its Correlation With Bone Metabolism In Patients With Rheumatoid Arthritis

Posted on:2023-01-12Degree:MasterType:Thesis
Country:ChinaCandidate:R X TangFull Text:PDF
GTID:2544306833951949Subject:Internal Medicine
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Objective Rheumatoid arthritis(RA)is a common autoimmune disease,and it is associated with osteoporosis(OP),which is one of the common causes of disability and deformity.To analyze the structural differences of intestinal flora between patients with rheumatoid arthritis(RA)and healthy people,investigate the relationship between intestinal microecology and bone metabolism in rheumatoid arthritis(RA),and seek new strategies to diagnosis and treat osteoporosis in patients with rheumatoid arthritis(RA).Method Sixty-two patients with RA who met the inclusion and exclusion conditions were selected and divided into group R(30 cases with RA and osteopenia)、group A(32 patients with RA and OP),according to bone mineral density(BMD).32 healthy volunteers were selected as healthy control group(group C).PCR was used to amplify the V3-V4 hypervariable region of 16S rRNA sequence,and then Illumina MiSeq platform was used to sequence these regions.Further diversity of intestinal flora at phylum,genus and species level,alpha diversity,beta diversity were analyzed.LEf Se clustering analysis was used to obtain the representative intestinal flora in each group.The PICRUSt software was used to predict the metagenome function of intestinal flora.The levels of rheumatoid arthritis-related antibodies,inflammatory indexes and bone metabolism indexes were observed in each group.Spearman correlation analysis was performed between these items and intestinal microflora.Results1.There was no significant difference in the diversity of intestinal flora between RA groups with different bone metabolism levels and healthy controls(P>0.05).2.The composition of intestinal flora was different among the three groups.At the phylum level,the ratio of Firmicutes to Bacteroidetes(F/B)in the RA group was significantly lower than that in healthy control group(P<0.05),but there was no statistical difference in F/B between different bone metabolism group(group R and group A)(P>0.05).At the genus level,compared with the healthy group(group C),the abundance of Megamonas and Agathobacter in the RA group(group R and group A)was significantly decreased(P<0.05),while the abundance of Escherichia-Shigella was significantly increased(P<0.05).The abundance of prevotella in RA with osteoporosis group(group A)was higher than that in RA with osteopenia group(group R)(P<0.05).At the species level,compared with the healthy group(group C),the abundance of gMegamonas was higher in RA group(P<0.05).Compared with group R and group C,UnculturedbacteriumgMegamonas、Bacteroidesplebeius significantly decreased in group A(P<0.05),and the abundance of gPrevotella9、gEscherichia-Shigella significantly increased(P<0.05).3.LEfSe analysis was conducted to find the representative bacteria among three groups,and the results showed that p-Firmicutes、g-Megamonas、g-Agathobacter were the representative bacteria in the healthy control group(group C).s-Bacteroides-plebeius was found in RA with osteopenia(group R).o-Enterobacteriales、f-Enterobacteriaccae were found in the RA with osteoporosis(group A).The difference was statistically significant(LDA values all were greater than 4).4.Rank sum test showed that,at the family level,there wrere differences among three groups in composition of flora,such as Enterobacteriaceae,Lactobacillaceae,Fusobacteriaceae,Bacillaceae and so on(P<0.05).5.KEGG showed that pyruvate metabolism,drug metabolism-other enzymes,fatty acid degradation,ascorbic acid and hyaluronic acid metabolism,microbial metabolism in different environments were increased in group A,compared with healthy control group(group C),and the biosynthesis of secondary metabolites,phenylprochloric acid chlorolysase synthesis,tyrochloric acid synthesis,and tryptophan synthesis were less.In group R,pyruvate metabolism,taurine metabolism and sutaurine metabolism were increased,and secondary metabolites biosynthesis were decreased.6.The results of Spearman correlation test and LEf Se analysis were all suggested Megamonas was negatively correlated with RF、β-CTX and ESR.Agathobacter was negative correlation with RF、anti-CCP antibody、CRP and ESR,but positive correlation with 25-hydroxy vitaminD.Escherichia coli was positively correlated with PINP、CRP and ESR,and negatively correlated with 25-hydroxy vitaminD.Conclusion The intestinal microecology(microflora and its metabolites)is imbalanced in RA patients,F/B is significantly reduced.The composition of intestinal microflora in groups with different bone metabolism levels(group A and group R)is diversity,at different classification levels(phylum,family,genus,species).The abundane of Escherichia and Prevotella was significantly increased in RA with OP group(group A).By searching for different bacteria and conducting correlation analysis,it was found that intestinal flora may directly or indirectly affect bone metabolism in RA through influencing inflammatory factors,bone metabolism markers and so on.
Keywords/Search Tags:Intestinal flora, Rheumatoid arthritis, Bone metabolism, 16S rRNA
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