Are Intestinal bacteria involved in the etiology of rheumatoid arthritis?

Abstract

Are intestinal bacteria involved in the etiology of rheumatoid arthritis? APMIS 100: 1-9, 1992. 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 by Sulmonellu, Shigellu and Yersiniu can 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 some Eubacterium and Bijidobacterium species induced a severe chronic polyarthritis in Lewis rats after a single intraperitoneal injection. Eubacterium was found in numbers of 108-109 per gram in stools of healthy subjects and rheumatoid arthritis (RA) patients. CWF of isolated strains of E. uerofuciens were 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 an E. aerofaciens CWF arthritis. A helper T-cell line B13 was in vivo arthritogenic in knee or ankle joints upon intravenous injection in rats and proliferated in vitro on syngeneic spleen cells alone, but was additionally stimulated by intestinal PG-PS and E. uerofaciens CWF. 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.

Gut bacteria and health foods—the European perspective

“…Furthermore, bowel infection by enteropathogens such as Salmonella and Yersinia can provoke joint inflammation in patients. These facts support the theory that intestinal bacteria play a role in the etiology of rheumatoid arthritis (Hazenberg et al, 1992). Possible mechanisms include altered bowel anatomy, autoimmunity due to molecular mimicry, altered bowel permeability, and toxin mediated synovitis (Phillips, 1989).…”

“…Possible mechanisms include altered bowel anatomy, autoimmunity due to molecular mimicry, altered bowel permeability, and toxin mediated synovitis (Phillips, 1989). Arthropathic properties of intestinal bacteria have been widely studied in animal models (for a review, see Hazenberg et al, 1992). However, in animal (rat) studies, the bacteria were most often introduced by intraperitoneal injection, which is an extreme situation and hardly reflects the situation in humans.…”

Dietary Glycine Prevents Peptidoglycan Polysaccharide-Induced Reactive Arthritis in the Rat: Role for Glycine-Gated Chloride Channel

“…PG-PS is retained in the joints and synovial fluid of some rheumatoid arthritis patients (16,22,37). Interestingly, overgrowth of small bowel bacteria induces reactivation of arthritis possibly due to PG-PS; however, the mechanism of the pathogenic actions of PG-PS is still unclear (11,29,34). PG-PS might induce a variety of persistent inflammatory diseases (i.e., carditis, granulomatus hepatitis, and enterocolitis) by production of cytokines and oxygen radicals (29).…”

Enzyme Degradation and Proinflammatory Activity in Arthritogenic and NonarthritogenicEubacterium aerofaciensCell Walls

“…The glycosidic bonds between MurNAc and GlcNAc are cut by the PG hydrolyzing enzymes mutanolysin and lysozyme. However, due to steric hindrance by associated polysaccharides and proteins, all bonds may not be reached by enzymes, resulting in fragments of different sizes.Since there is increasing attention on intestinal bacteria as potential triggers of rheumatoid arthritis (7,14,28,31,37,46), we have studied here why two nearly identical representatives of the human normal gut flora are so different in their arthritogenic capacity. For this purpose, CWs of the two E. aerofaciens strains were examined for degradation by mutanolysin and lysozyme and for their capacity to stimulate production of proinflammatory cytokines.…”