Saccharomyces boulardii (CNCM I-745) alleviates collagen-induced arthritis by partially maintaining intestinal mucosal integrity through TLR2/MYD88/NF-κB pathway inhibition.

BACKGROUND

Rheumatoid arthritis, a condition characterized by inflammation, has a substantial influence on both the worldwide economy and public health. Prior studies indicate that probiotics have the potential to enhance the composition of gut microbiota in instances of intestinal dysbiosis resulting from different disorders and contribute to the regulation of inflammation. The objective of this study is to investigate the impact of Saccharomyces boulardii on the gut microbiome in arthritis and its implications on inflammation.

METHODS

The study utilized the Collagen Induced Arthritis (CIA) Sprague-Dawley (SD) rat model. After administering Saccharomyces boulardii (150 mg/kg/day) six days a week and Methotrexate (MTX) (0.2 mg/week) treatment for eight weeks, microbial DNA from the feces was sequenced using 16S rRNA. The evaluation of histopathology, bone loss, and cartilage degradation was conducted using histology, immunohistology assays, and micro-computed tomography (µCT) examinations. The enzyme-linked immunosorbent assay (ELISA) was used to analyze proinflammatory cytokines, while the western blot technique was applied to detect protein in the gut and in cell lines. The quantification of gene expression in gut,joint and cell lines was performed using real-time polymerase chain reaction. The cell lines were activated and then treated with the culture supernatant of S. boulardii for an in vitro investigation. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was utilized to assess cell proliferationand viability. Cellular motility was measured in a wound healing experiment, whereas apoptotic proteins were analyzed using Western blotting.

RESULTS

S. boulardii has been found to enhance bone and joint integrity, modulate gut microbiota, and mitigate proinflammatory cytokine levels in rats with arthritis. It decreases the permeability of the intestines and promotes the production of gut tight-junction proteins. The administration of S. boulardii inhibits the proliferation of T-helper-17 (Th17) and Type 3 innate lymphoid cells (ILC3). Additionally, it elicits apoptosis in MH7A cell lines and hinders their migratory activity.

CONCLUSION

This study provides valuable insights into the therapeutic potential of S. boulardii for treating and preventing arthritis in rats with collagen-induced arthritis by modulating gut microbiota and inflammation.