Several publications in the last 2-3 years brought more interest in the link between gut and gingival bacteria or microbiota, and human health and diseases, and particularly their possible game changer role in the pathogenesis of rheumatoid arthritis.
The human gastrointestinal tract comprises approximately 1014 bacterial microbes and amounts to a biomass of approximately 2 kg, and according to some estimates this corresponds to a ratio for microbial to human cells approximately 1.3:1 (cf. JD Forbes, G Van Domselaar & CN Bernstein, Front Microbiol. 2016; 7: 1081).
There is now an increasing body of evidence suggesting that alterations of gut flora are common in some immune-mediated inflammatory diseases such as inflammatory bowel disease, multiple sclerosis and rheumatoid arthritis (RA).
Gut bacteria as a pathogenic factor in RA was perhaps first recognized in 1965 by Mansson and Colldahl reporting increased amounts of Clostridium perfringens type A in the intestinal flora of RA patients. This later became clear to be a non-specific findings, as being recorded in other chronic arthritides.
Periodontitis (PD)-associated bacteria, e.g., Porphyromonas gingivalis are often linked to chronic inflammatory oral disease, and, interestingly, RA and the severe forms of PD share several features, such as increased levels of pro-inflammatory cytokines and metalloproteinases. In fact, Porphyromonas gingivalis was suggested to provide a trigger for the development of RA, also being the only known bacterium carrying a peptidyl-arginine-deiminases (PAD) enzyme.
Of note, the first case of a complete recovery after periodontal treatment, in a patient with newly onset of RA has been recently reported, suggesting that prompt periodontal infection treatment may eventually induce disease regression.
According to Jose U. Scher et al. the microbiome may contribute causally to RA through 3 major mechanisms. This includes the ‘state of dysbiosis’, a possible ‘provision of neoantigens’ (i.e., P. gingivalis–driven citrullination of peptides and generation of ACPAs – the anti–citrullinated protein antibodies), and/or the ‘generation of costimulatory signals’. In this one, e.g., in the presence of potentially arthritogenic ACPAs, the disease is triggered only through a “second event,” driven by bacterial components and consequent cellular immune response.