Translocation of intestinal peptidoglycan moieties modulates the early stages of arthritis.

Abstract

Abstract Intestinal barrier dysfunction may contribute to the development of chronic arthritis, but the underlying pathophysiological mechanisms are not fully understood. We took advantage of induced and spontaneous models of murine arthritis to study how translocation of peptidoglycan (PG) and its fractions impact the course of chronic arthritis. We experimentally increased the translocation of intestinal bacterial cell envelope moieties using oral gavage of muramyldipeptide (MDP) and lipopolysaccharide (LPS), as well as genetic (deletion of intestinal Hnf-4a) and nutritional (food additive carrageenan) perturbations of intestinal barrier function. Oral gavage with MDP and LPS increased arthritis without altering the gut barrier integrity. Translocated PG from the gut to blood and spleen was correlated with the severity of arthritis. Carrageenan treatment increased translocation of PG into the joints, and worsening of arthritis. Interestingly, MDP, LPS and dietary factors worsened the course of arthritis only when administered before, but not after, the onset of arthritis. In human patients, MDP was more abundant in the synovial fluids of children with Juvenile Idiopathic Arthritis than in those of children with transient forms of arthritis. In conclusion, there is a window during the early stages of arthritis, when translocation of gut bacterial components can modulate the progression of arthritis.