Intestinal anaerobic bacteria in early rheumatoid arthritis (RA)

Abstract

Increasing attention has recently been paid to the normal intestinal flora as a potential source of etiological agents in RA. Changes in the intestinal flora, due to fasting or diet, have been shown to reflect improvement of the patients when they are divided into high and low-responders. Previously, evidence has also been presented that intestinal flora in the early RA is different from that of non-RA controls, due primarily to anaerobic bacteria. The present study was designed to compare the fecal microbiota of the patients with early RA with the microbiota of the control patients using 16SrRNA oligonucleotide probes, detecting a variety of anaerobic bacteria in the normal intestinal flora. Fecal samples of 25 early, disease modifying antirheumatic drugs, naive RA patients and 23 control patients suffering from noninflammatory pain were investigated. The contribution of five bacterial groups was determined by using whole cell hybridization with seven fluorescently labeled 16SrRNA-targeted oligonucleotide probes. These probes cover one third to a half of the total bacteria in the human intestine. Patients with early RA had significantly less bacteria belonging to the Bacteroides, Prevotella and Porphyromonas genera than the controls (4.7% vs. 9.5%, P = 0.00005). The finding was confirmed with a probe specific for bacteria of the Bacteroides fragilis group (1.6% vs. 2.6%, P = 0.02). The samples of RA patients and the controls did not differ significantly when five other oligonucleotide probes were applied. They were detecting bacteria in the genera Atobium, Coriobacterium, Collinsella, Bifidobacterium and Fusobacterium, and in the Eubacterium rectale-Clostridium coccoides group. We conclude that the content of anaerobic bacteria in the intestinal flora of the patients with early RA is significantly different than that of the controls. The number of bacteria belonging to the Bacteroides-Prevotella-Porphyromonas group was, on average, in RA patients only half that of the controls. If this finding can be confirmed, together with a recent suggestion that certain Bacteroides species are required for fortification of the barrier function in the intestinal epithelium, it adds further evidence to the hypothesis that intestinal bacterial flora plays a role in the etiopathogenesis of RA.