Rheumatoid arthritis: an anti-TNF-alpha drug is shown to improve gut dysbiosis

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The administration of etanercept, an anti-TNF-alpha drug, induces partial restoration of the gut microbiota in patients with dysbiosis caused by rheumatoid arthritis.

 

What is the impact of rheumatoid arthritis (RA) and its treatment on the gut microbiota, and viveversa? To answer this question that comprises two major issues, an Italian team conducted a pilot study comparing bacterial populations in 10 healthy subjects and 42 RA patients who were either treatment-naïve or treated with methotrexate and/or etanercept. In addition to this comparison, the effects of the main bacteria present in patients with RA on the physiological and immunological parameters of the disease were assessed.

Gut dysbiosis corrected with an anti-TNF-alpha drug

The comparison of the gut microbiota of treatment-naïve patients and that of healthy volunteers confirms the findings described in the literature: although overall bacterial abundance and diversity are not impacted by RA, the disease is associated with a change in bacterial populations (increase in Lactobacillales and Bacilli levels, decrease in Flavobacterium and Faecalibacterium levels –the latter being known for its anti-inflammatory properties). Post-treatment analysis of the microbiota showed a significant improvement in gut microbiota, especially when etanercept was used: the authors indicate that there were higher levels of cyanobacteria, capable of producing secondary metabolites with anti-inflammatory and immunosuppressant properties that are potentially beneficial to patients.

Clinical parameters associated with the gut microbiota

The analysis of correlations between gut bacterial populations and RA clinical parameters shows multiple associations, particularly between pro-inflammatory Gammaproteobacteria and disease activity (based on the DAS-28* score), as well as between bacteria from the Enterobacteriales family and erythrocyte sedimentation rate. The Euryarchaeota phylum, directly correlated to DAS score, also seems to be an independent risk factor for the disease. All these results confirm the role of the gut microbiota in the etiopathogenesis of rheumatoid arthritis and demonstrate for the first time that an anti-TNF-alpha drug can induce partial restoration of specific gastrointestinal bacteria that promote therapeutic efficacy.

 

*DAS (Disease Activity Score) and its simplified version, DAS-28, are measures of disease activity in rheumatoid arthritis developed by the European League Against Rheumatism (EULAR).

 

Sources:

Picchianti-Diamanti A, Panebianco C, Salemi S, et al. Analysis of Gut Microbiota in Rheumatoid Arthritis Patients: Disease-Related Dysbiosis and Modifications Induced by Etanercept. Int. J. Mol. Sci. 2018, 19, 2938; doi:10.3390/ijms19102938