Are Intestinal bacteria involved in the etiology of rheumatoid arthritis?

Publisher Website
Google Scholar
Abstract
Observations in bowel‐related joint diseases give support to this hypothesis. In Crohn's disease and ulcerative colitis, the bowel wall inflammation is complicated in about 20% of the patients by joint inflammation. Bowel infection bySalmonella, ShigellaandYersiniacan provoke joint inflammation and supports an etiological link between bowel bacteria and arthritis. The arthropathic properties of the most abundant group of intestinal bacteria, i.e. the obligate anaerobic bacteria, were studied in an animal model. Cell wall fragments (CWF), with peptidoglycan as the major component, from someEubacteriumandBifidobacteriumspecies induced a severe chronic polyarthritis in Lewis rats after a single intraperitoneal injection.Eubacteriumwas found in numbers of 108‐109per gram in stools of healthy subjects and rheumatoid arthritis (RA) patients. CWF of isolated strains ofE. aerofacienswere arthropathic. Soluble peptidoglycan polysaccharide complexes (PG‐PS) originating from the obligate anaerobic flora were purified from human intestinal contents. PG‐PS from ileostomy fluid that proved to be less processed by intestinal enzymes induced chronic arthritis in rats after a single administration in oil in the base of the tail. It was concluded that the human intestinal bowel contains soluble bacterial cell wall products that are arthropathic in an animal model. Peptidoglycan (PG) or its subunits was reported to be present in mammalian tissues. Immunohistochemical studies from our group showed the presence of intestinal PG‐PS in sections of normal rat spleen. Bacterial cell wall or PG‐induced joint inflammation in rats is proven to be absolutely dependent on functional T cells. T‐cell lines were isolated from the lymph nodes of rats with anE. aerofaciensCWF arthritis. A helper T‐cell line B13 wasin vivoarthritogenic in knee or ankle joints upon intravenous injection in rats and proliferatedin vitroon syngeneic spleen cells alone, but was additionally stimulated by intestinal PG‐PS andE. aerofaciensCWF. It was postulated that the arthritogenic T cells that seem to be autoreactive are, in fact, recognizing bacterial PG‐PS on antigen‐presenting cells (APC). It is generally accepted that RA is a T‐cell‐dependent process and that therefore the reaction is directed at small peptides bound by the major histocompatibility complex of APC. The only peptides present in arthritis inducing intestinal PG‐PS and in CWF are PG peptides interlinking the sugar chains. We feel that the immunoreaction against PG peptides plays a pivotal role in experimental and human arthritis of an unknown etiology.

This publication has 51 references indexed in Scilit: