This association followed the identification of significant reductions in this microbial strain in the human cohorts with a history of, or currently suffering from RA.
While RA manifests as synovial hyperplasia, synovial inflammation, pannus formation and destruction of cartilage and joints, it has been increasingly recognised that there is dysbiosis of the gut microbiota occurring in these patients.
With a previous study noting the occurrence of significant dysbiosis and mucosal inflammation in arthritic mice, there is an established need for further investigation to provide a greater understanding of the role of the gut microbiota in the disease.
As a result, the present study sought to investigate the efficacy of probiotic use and the specific strains with the potential to preventing disease development.
Their research leads the team to present the gut microbe P. distasonis as a probiotic and ginsenoside Rg2 as a prebiotic agent for the treatment of RA.
Genetic sequencing in a human cohort suffering from RA was used to establish the resultant metagenomics. Additionally, mice models with collagen-induced arthritis, as well as TNF-α transgenic models were utilised to assess the role of Parabacteroides distasonis. The effects on CD4+ T cells as well as on macrophage differentiation following additional administration of the strain’s metabolites were also analysed.
It was observed in the human cohort that new-onset patients had significant reductions in numbers of P. distasonis, as well as in those with an established history of RA. “This decrease was negatively correlated with Disease Activity Score-28 (DAS28)”, the researchers note.
Following this, after oral administration with live P. distasonis, it was observed that there was a markedly reduced sensitivity in the arthritic mice models to RA. This resulted from shifting the Th17/Treg cell balance (Th17 cells are proinflammatory, while Treg cells are anti-inflammatory), improving intestinal permeability, and neutralising pathogenic antibodies.
In addition, it was established from the drug screening, that ginsenoside Rg2 could be a potential prebiotic to exhibit similar effects in reducing symptoms associated with RA.
The report results show a clear association between P. distasonis and the pathogenesis of RA in the mice models, suggesting a possible probiotic treatment intervention for preventing the disease onset.
“In patients with RA, the Th17/Treg balance is skewed in favour of Th17 cells, leading to the development of autoimmunity and systemic inflammation. Improvement of the Th17/Treg cell balance is an important strategy for suppressing experimental arthritis. Our flow cytometry results showed that P. distasonis treatment corrected the Th17/Treg imbalance in the spleen, mesenteric lymph nodes (MLNs) and central lymph nodes (CLNs).”, the researchers explain.
“Mounting evidence characterises that the gut epithelial barrier perturbation links the relationship between gut microbiota dysbiosis and the development of RA. Restoration of tight junction integrity could ameliorate the development of RA.”, they add.
“Our study presents the gut microbe P. distasonis as a probiotic and ginsenoside Rg2 as a prebiotic agent for the treatment of RA.”, the researchers conclude, however further study is required with administration involving a human cohort. In addition, long-term RCTs would enable for the control of potential cofounders whilst providing validity to the observed association.
“Gut commensal Parabacteroides distasonis alleviates inflammatory arthritis”
Haijian Sun, Yunke Guo, Haidan Wang, Ailing Yin, Jing Hu, Tianjie Yuan, Shuxin Zhou, Weichen Xu, Peng Wei, Shusheng Yin, Panru Liu, Xi Guo, Yizhao Tang, Yujiao Yan, Zichen Luo, Majie Wang, Qingqing Liang, Peng Wu, Aifeng Zhang, Zhuxiu Zhou, Yueyue Chen, Yongming Li, Jing Li, Jinjun Shan, Wei Zhou