Intestinal Dysbiosis is Present in Many Patients with RA

Kristofer Andréasson, MD, PhD

Credit: X.com

Internal dysbiosis is a common feature of rheumatoid arthritis (RA), although certain treatments—such as methotrexate or tumor necrosis factor inhibitors (TNFs)—can modulate the gastrointestinal microbiota among these patients, according to a study published in Open Rheumatology.¹

Previous research has indicated a link between immune response to microbes in the intestines and synovial inflammation among patients with RA and cross-sectional studies have shown the presence of dysbiosis in early and established cases of RA. Additionally, Prevotella copri (P. copri) have been linked to both RA and the development of RA.²

“To date, few studies have explored the intestinal microbiota in relation to usage of immunomodulatory treatments in RA,” wrote a team of investigators led by Kristofer Andréasson, MD, PhD, associated with Lund University in Sweden. “[However,] small, prospective studies have suggested that successful methotrexate therapy in patients with RA may partially normalize the intestinal microbiota and that specific microbial alterations may predict treatment response to methotrexate.”

Investigators assessed changes in intestinal microbial composition in patients with RA beginning treatment with TNF or methotrexate using a stool sample upon initiation and a follow-up sample 3 months later. Eligible patients met the classification criteria for RA between February 2016 and March 2018. These patients were included in the analysis regardless of disease duration and disease-modifying antirheumatic drug (DMARD) treatment in the TNF cohort if they had received it for 3 months prior to study initiation and it remained unchanged during the study period.

To determine the presence and degree of dysbiosis, a 16S ribosomal RNA gene-based validated microbiota test was performed. The fecal levels of P. copri were evaluated using a quantitative polymerase chain reaction. Any changes in microbial composition were assessed in relation to disease activity, which was measured using the disease activity score based on 28-joint counts using C-reactive protein (DAS28-CRP).

The mean age of patients at baseline was 58 years, most (78%) were female, and the median disease duration was 4.4 (.7 — 12) years. Most patients reported moderate disease activity at baseline and disease duration was lower in patients treated with methotrexate compared with TNF (median .4 vs 6.4 years, respectively).

Internal dysbiosis was present in 66% (n = 33/50) of patients at baseline and was more common among those with a disease duration of > 2 years (P = .019). At the 3-month follow-up appointment, the GA-map Dysbiosis Index Score (DIS) improved in 14 (28%) patients and 27 (54%) were deemed good treatment responders. Those receiving TNF treatment were more likely to exhibit improved DIS compared with patients in the methotrexate group (P = .031).

P. copri was reported in 64% (n = 32/50) of patients at baseline. Improvements in DAS28-CRP were associated with decreases in P. copri abundance (P = .036).

Investigators noted limitations including using the DIS to analyze the fecal samples as it has limited power to identify bacterial strains. Based on the findings of the study, future research should use high-throughput sequencing of the full metagenome. Additionally, there is a possibility that confounding factors could have contributed to the differences among patients receiving TNF and methotrexate due to the observational nature of the study.

Despite these limitations, the study was strengthened by its prospective design, inclusion of consecutive patients receiving both treatment approaches, and its prespecified objectives and outcomes.

“Future prospective studies in larger cohorts, encompassing analysis of the complete intestinal microbiome, are needed to validate these results and further explore the relevance of microbial changes induced by immunosuppression in RA,” investigators concluded.

References

1. ^{Andréasson K, Olofsson T, Lagishetty V, et al. Treatment for Rheumatoid Arthritis Associated With Alterations in the Gastrointestinal Microbiota. ACR Open Rheumatol. Published online April 23, 2024. doi:10.1002/acr2.11673}
2. ^{Scher JU, Sczesnak A, Longman RS, et. al. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. Elife 2013; 2:e01202.}