Rheumatoid arthritis: the gut microbiota is altered from the early stages

Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting joints and characterized by synovial membrane inflammation which reaches surrounding bones and cartilages. For some years the gut microbiota has been the focus of increasing interest from the scientific community, who believes it is involved in RA.

Dysbiosis observed as soon as the early stages

While previous works had already reported dysbioses in patients at an advanced stage of the disease, a Korean team focused on the early stages, and exclusively on women, who are more affected by RA. The 29 female patients included in the study were either at a preclinical stage (PC, n=17), or with clinically apparent early-stage RA (ER, n=12), and were DMARD-naive (DMARD = disease-modifying antirheumatic drugs). The bacterial DNA from fecal samples extracted from patients was compared to that of 25 control healthy women. First finding: the microbiota of patients with RA was characterized by a lesser bacterial diversity (without any difference between PC and ER patients). Moreover, differences were observed in the present bacterial species: for instance, bacteria from the Bacteroidetes phylum were over-represented in patients with RA, while those from the Actinobacteria phylum were under-represented, especially those from the Collinsella genus.

Altered genetic functions

These differences in composition were reflected in genetic differences: genes involved in the synthesis of ubiquinone (co-enzyme Q10) and menaquinone (vitamin K2) were more abundant in controls, while genes involved in the transport and absorption of iron were more abundant in patients with RA. This characteristic, which promotes the absorption of iron by bacteria from the microbiota, could explain the anemia often observed in people with RA. Finally, genes coding for the synthesis of lipopolysaccharides–molecules expressed on the surface of gram-negative bacteria which cross the gut barrier and promote systemic inflammation–were especially represented in female patients with clinically apparent RA. This is an astounding result regarding the inflammatory nature of RA. Larger studies based on complementary sequencing studies could specify the role of the gut microbiota in RA and determine whether dysbiosis is a cause or a consequence of the disease.