Protective effect of Bacteroides fragilis LPS on Escherichia coli LPS-induced inflammatory changes in human monocytic cells and in a rheumatoid arthritis mouse model

Abstract

It has been reported that patients with rheumatoid arthritis (RA) have significantly less bacteria belonging to the Bacteroides group in their microbiota. We speculate that inhibition of cytokine production is impaired in patients with RA owing to their low levels of intestinal bacteria belonging to the Bacteroidetes group. Here we investigated the effect of Bacteroides fragilis lipopolysaccharide (B-LPS) on cytokine production in vitro and on the development of collagen antibody-induced arthritis (CAIA) in DBA/1 mice, an animal model of RA. in vitro culture experiments showed that Escherichia coli LPS (E-LPS)-induced cytokine production from THP-1 monocytic cells and peripheral blood mononuclear cells was significantly suppressed by B-LPS in a dose-dependent manner. A decrease in TNF-α and IL-1β production was also observed in LPS-tolerized macrophages induced by B-LPS at concentrations equal to and higher than that of E-LPS. Similar results were obtained when autoclaved feces were used to induce cytokine production instead of E-LPS. In in vivo experiments using CAIA models, B-LPS had no adverse effects even when administered at 10 times the concentration of E-LPS, which elicits severe arthritis. In addition, simultaneous administration of high dose B-LPS with E-LPS or administration of B-LPS prior to E-LPS significantly suppressed arthritis development in CAIA model animals when compared with administration of E-LPS alone. These results suggest that increasing certain bacterial groups such as Bacteroides is an effective strategy for preventing arthritis development in patients with RA.