Bacillus subtilis (NMCC-path-14) ameliorates acute phase of arthritis via modulating NF-κB and Nrf-2 signaling in mice model

Probiotics (PBT) have been extensively studied as an adjunct therapy for various inflammatory conditions. This is because inflammation often leads to dysbiosis, a microbial imbalance that can be corrected using PBT. Most research has focused on Lactobacillus, with limited data on Bacillus PBT for alleviating CFA-induced arthritis in animal models. While most studies focus on the chronic aspect of CFA-induced arthritis, our current research aims to evaluate the effects of pre-treatment, concurrent treatment, and post-treatment with Bacillus subtilis (NMCC-path-14) against the acute phase of arthritis induced by CFA in the mice model. Arthritis was produced by administering CFA into the subplantar region of the mouse's right hind paw. Pain-related behavioral parameters, antioxidant capacity, histological and radiological parameters, expression of essential cytokines, and DNA damage were assessed during the acute phase. B. subtilis treatment significantly reduced the paw edema and improved the arthritic index. The nocifensive threshold was also raised, and muscle coordination improved considerably after B. subtilis treatment on days 7 and 14. The antioxidant capacity and histological and radiological parameters were also enhanced. We demonstrated that B. subtilis therapy preserved the DNA during the acute phase of arthritis using the Comet assay. Comparing results to the arthritic control, a significant reduction was observed in the expression levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and nuclear factor-kappa B (NF-κB). In contrast, the level of nuclear factor erythroid 2-related factor 2 (Nrf-2) was enhanced. During the acute phase of the disease, B. subtilis displayed a potent anti-inflammatory and anti-arthritic action against CFA-induced arthritis.