Abstract
Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation of the joints and extra-articular manifestations. Recent studies have shown that microorganisms affect RA pathogenesis. However, few studies have examined the microbial distribution of early RA patients, particularly female patients. In the present study, we investigated the gut microbiome profile and microbial functions in early RA female patients, including preclinical and clinically apparent RA cases. Changes in microbiological diversity, composition, and function in each group were analyzed using quantitative insights into microbial ecology (QIIME) and phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt). The results revealed the dysbiosis due to decreased diversity in the early RA patients compared with healthy subjects. There were significant differences in the microbial distribution of various taxa from phylum to genus levels between healthy subjects and early RA patients. Phylum Bacteroidetes was enriched in early RA patients, while Actinobacteria, including the genus Collinsella, was enriched in healthy subjects. Functional analysis based on clusters of orthologous groups revealed that the genes related to the biosynthesis of menaquinone, known to be derived from gram-positive bacteria, were enriched in healthy subjects, while iron transport-related genes were enriched in early RA patients. Genes related to the biosynthesis of lipopolysaccharide, the gram-negative bacterial endotoxin, were enriched in clinically apparent RA patients. The obvious differences in microbial diversity, taxa, and associated functions of the gut microbiota between healthy subjects and early RA patients highlight the involvement of the gut microbiome in the early stages of RA.
Highlights
Rheumatoid arthritis (RA) is a representative autoimmune disorder characterized by inflammation in the synovial membrane of joints that spreads to inflammation in the surrounding cartilage and bone, resulting in joint destruction and deformation [1]
To investigate whether RA is associated with altered microbial diversity, we sequenced fecal samTpoleisnfvreosmtig2a5tehewahltehtyhesrubRjAectiss aanssdo2ci9ateeadrlywRithAafletmeraelde mpaitcireonbtisa(lTdaibvleers1i)tya,nwdeasneaqlyuzeendcetdhefedcaatla suamsinpglesqifirmome22-250h1e8a.1lt1h.yAsfutberjecfitlstearnindg2,9meaerrlgyinRgAafnemd arleempoavtiienngtsc(hTiambelera1)aannddPahniaXlyszeeqdutehnecdeas,ta5u43si,2n5g9 qrieimades2-w20e1re8.c1l1u.sAtefrteedr fiinltteoriOngT,Umsebragsinedg oannd97re%msoevqiunegnccheimsimerialaarnitdyP, whiiXthseaqmueenanceos,f 51403,0,26509rreeaaddssawcreorses ctlhueste5r4edsainmtoplOesT.UTshbeapsehdyolong9e7n%etsiceqduievnecresistiymoilfatrhitey, gwuitthmaimcreoabniootfa1o0,f0E60Rrepaadtiseanctrsosws aths es5ig4nsiafmicapnletlsy
These differences between the two studies may be to due to differences between subjects; the present study was carried out on drug-naïve early RA female patients whereas the previous study was conducted on RA patients including those treated with various medications
Summary
Rheumatoid arthritis (RA) is a representative autoimmune disorder characterized by inflammation in the synovial membrane of joints that spreads to inflammation in the surrounding cartilage and bone, resulting in joint destruction and deformation [1]. The introduction of SFB into germ-free mice caused induction of lamina propria Th17 cells, production of autoantibodies, and arthritis [6]. Th17 cells were increased in the large intestine of SKG mice treated with Prevotella copri from the microbiota colonizing RA patients [7]. Microbial diversity was found to be reduced in RA patients in various studies, resulting in gut microbiota dysbiosis [8]. Studies on Chinese patients reported that Lactobacillus was increased in cases of very active RA [8], and in new onset RA patients, Prevotella copri was more abundant than in healthy subjects but less abundant in established RA cases [10]. Prevotella copri was more enriched in individuals at risk for rheumatoid arthritis compared with their first degree relatives [11]
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