Extra-intestinal translocation of microbes and tissue specificity in rheumatic musculoskeletal disease (RMD): its more than a gut feeling

By Timothy R D J Radstake


Millions of micro-organisms populate our orifices from the moment we are born until we die. The microbiome represents the totality of micro-organisms that coexist with us rather peacefully and which we acquire purposefully from our environment. Health is associated with a balance between commensal and pathogenic microbes, which control the intestinal barrier integrity through the production of mucus and lipid metabolites, such as short-chain fatty acids. In the case of a disbalance (dysbiosis), leakage of these microbial products negatively affects the immune system, thereby contributing to a chronic proinflammatory state or worse, cancer. Accumulating evidence implicates the microbiota to a plethora of diseases among which rheumatological musculoskeletal disease (RMD).

For instance, the idea that the microbiota is associated with the development of rheumatoid arthritis (RA) has been put forward by several investigators, many of those who have sought the link to intestinal microbes. On a different take, the oral microbiota, more specifically the presence of Porphyromonas gingivalis, in patients with RA with accompanying periodontitis has been linked to the presence of anticitrullinated protein antibodies. In addition, dendritic cells from patients with RA were reported to have a blunted response towards Porphyromonas gingivalis further supporting the notion of an altered systemic immune response to microbiota in RA. More recently, the proposed relation between the microbiota and RMD has been extended to systemic sclerosis and primary Sjogrens syndrome.


Annals of the Rheumatic Diseases, 2018 Viewpoint