Analysis of Gut Microbiota in Rheumatoid Arthritis Patients: Disease-Related Dysbiosis and Modifications Induced by Etanercept

Abstract

A certain number of studies were carried out to address the question of how dysbiosis could affect the onset and development of rheumatoid arthritis (RA), but little is known about the reciprocal influence between microbiota composition and immunosuppressive drugs, and how this interaction may have an impact on the clinical outcome. The aim of this study was to characterize the intestinal microbiota in a groups of RA patients treatment-naïve, under methotrexate, and/or etanercept (ETN). Correlations between the gut microbiota composition and validated immunological and clinical parameters of disease activity were also evaluated. In the current study, a 16S analysis was employed to explore the gut microbiota of 42 patients affected by RA and 10 healthy controls. Disease activity score on 28 joints (DAS-28), erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, anti-cyclic citrullinated peptides, and dietary and smoking habits were assessed. The composition of the gut microbiota in RA patients free of therapy is characterized by several abnormalities compared to healthy controls. Gut dysbiosis in RA patients is associated with different serological and clinical parameters; in particular, the phylum of Euryarchaeota was directly correlated to DAS and emerged as an independent risk factor. Patients under treatment with ETN present a partial restoration of a beneficial microbiota. The results of our study confirm that gut dysbiosis is a hallmark of the disease, and shows, for the first time, that the anti-tumor necrosis factor alpha (TNF-α) ETN is able to modify microbial communities, at least partially restoring a beneficial microbiota.

Emerging Insights on the Interaction Between Anticancer and Immunosuppressant Drugs and Intestinal Microbiota in Pediatric Patients

“…When compared with naïve patients, significant changes were recorded in patients treated with etanercept: phylum Cyanobacteria significantly increased, in particular, in the Nostocophycideae class. In the group of patients treated with methotrexate, a decrease in the amount of Enterobacteriales (Proteobacteria) was described, whereas no significant variations were seen in patients treated with etanercept and methotrexate …”

“…Enterococcaceae ALL Microbiota and ALL susceptibility ↑ in ALL patients a 67 Microbiota and ALL susceptibility ↑ after therapy 68 Microbiota and ALL susceptibility ↑ chemotherapyinduced HEM and GI toxicity 68 Microbiota and ALL susceptibility ↑ after therapy 68 Mouse 95 ALL, acute lymphoblastic leukemia; GI, gastrointestinal; HEM, hematological; IBD, inflammatory bowel disease; JIA, juvenile idiopathic arthritis; NSAIDs, nonsteroidal anti-inflammatory drugs; PD-1, programmed cell death 1.…”

“…In the group of patients treated with methotrexate, a decrease in the amount of Enterobacteriales (Proteobacteria) was described, whereas no significant variations were seen in patients treated with etanercept and methotrexate. 95 Microbiota species involved in JIA therapeutics metabolism Studies on the effect of drug therapy on microbiota are still limited, especially in children. Methotrexate is a very important medication also for the treatment of JIA and it is known that intestinal microbiota in rodent models can modify this drug, but the implication of this finding in patients still needs to be explored.…”

Heightened Levels of Antimicrobial Response Factors in Patients With Rheumatoid Arthritis

“…A pathogenic role for Porphyromonas gingivalis, an oral commensal was also reported (19,20). These changes in the gut, oral and lung microbiome could cause the leakage of bacterial products into circulation, promoting inflammation and aggravating disease (20)(21)(22)(23)(24).…”

Influence of Diet and Nutrition on Prostate Cancer

“…Additionally, there is increasing interest regarding host interaction with gut microbiota based on the increased accessibility introduced by advances in technology. Interestingly, studies suggest that gut microbiota is involved not only in intestinal diseases but also in diseases in other organs, with several laboratory and human studies suggesting its involvement in Alzheimer's disease [137,138], rheumatoid arthritis [139,140], and diabetes [141,142]. Additionally, the influence of gut microbiota on cancer is a research area that has received substantial attention based on findings that gut microbiota, which is altered by various external factors, including dietary composition, is involved in all stages of cancer, including initiation, progression, treatment outcomes, and adverse reactions [143].…”