Intestinal Dysbiosis and Rheumatoid Arthritis: A Link between Gut Microbiota and the Pathogenesis of Rheumatoid Arthritis

Table 2

Summary of studies that have evaluated the influence of gut flora on the etiopathogenesis of RA.

Author (year of publication)	Design	Subjects included	Method employed	Results in the RA group versus the controls
Shinebaum et al. [70]	Case-control	25 patients with RA compared with controls	Estimation of bacterial counts in fecal culture	Significantly higher carriage rate of Clostridium perfringens in the RA population than controls (88% versus 48%, ). Coliform counts also tended to be higher
Eerola et al. [69]	Case-control	74 treatment-naive early RA and 91 non-RA controls	Gas-liquid chromatography of bacterial CFAs	Variation in CFA profile of RA as compared to controls likely caused by anaerobic bacteria
Vaahtovuo et al. [16]	Case-control	50 individuals with RA and 50 individuals with fibromyalgia	Flow cytometry, 16S rRNA hybridization, and DNA-staining	The RA patients had significantly less bifidobacteria and bacteria of the Bacteroides-Porphyromonas-Prevotella group, Bacteroides fragilis subgroup, and Eubacterium rectale-Clostridium coccoides group
Toivanen et al. [57]	Case-control	25 treatment-naive individuals with early RA patients and 23 control patients suffering from noninflammatory pain	16S ribosomal DNA	Patients with early RA had significantly less bacteria belonging to the Bacteroides, Prevotella, and Porphyromonas genera than the controls (4.7% versus 9.5%, ). The number of bacteria belonging to the Bacteroides-Prevotella-Porphyromonas group was, on average, in RA patients only half that of the controls
Scher et al. [18]	Cross-sectional	44 treatment-naive individuals with RA, 26 treated RA, 16 patients with psoriatic arthritis, and 28 healthy controls	16S ribosomal DNA	Increases in Prevotella copri (75% versus 21.4%) abundance and decrease in Bacteroides
Liu et al. [56]	Case-control	15 individuals with early RA and 15 healthy controls	Quantitative real-time PCR	Fecal microbiota of RA patients contained significantly more Lactobacillus (10.62 ± 1.72 copies/g) than the control group (8.93 ± 1.60 copies/g)
Zhang et al. [5]	Cohort	77 treatment-naive individuals with RA and 80 unrelated healthy controls; 17 treatment-naive individuals with RA paired with 17 healthy relatives; and 21 samples from DMARD-treatedindividuals with RA	Metagenomic shotgun sequencing and a metagenome-wideassociation study	The RA gut was enriched in gram-positive bacteria and depleted of gram-negative bacteria, including some Proteobacteria and gram-negative Firmicutes of the Veillonellaceae family. The RA-enriched MLGs formed a large cluster including Clostridium asparagiforme, Gordonibacter pamelaeae, Eggerthella lenta, and Lachnospiraceae bacterium. There was a trend towards increased abundance of P. copri as a function of RA duration in the first year
Maeda et al. [63]	Cross-sectional	25 treatment-naive individuals with early RA patients and 23 healthy controls	16S rRNA-based deep sequencing	A subpopulation of early RA patients harbored intestinal microbiota dominated by Prevotella copri
Chen et al. [55]	Case-control	40 Subjects with RA with treatment	16S ribosomal DNA	Increased number of reads from the phylum Actinobacteria in the RA group (0.45 versus 0.04%)
		32 controls (15 relatives of 1 degree with AR and 17 healthy subjects)		Decrease in Faecalibacterium and expansion of Collinsella aerofaciens and Eggerthella lenta

MLGs: metagenomic linkage groups.