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Updated: Jun 12, 2025

An Adoptive Transfer Model of Rheumatoid Arthritis in Mice
Published on: June 6, 2025
Protective potential of Bacillus subtilis (NMCC-path-14) against extraarticular manifestations during acute and
Muhammad Usama Mazhar1, Sadaf Naz1, Jehan Zeb Khan1
1Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
Abstract:
Extra-articular manifestations (EAM), which are associated with rheumatoid arthritis (RA), affect the quality of life of patients and are one of the critical causes of early mortality. This study was aimed at investigating whether Bacillus subtilis NMCC-path-14 (1 × 108 CFU/animal/day) could serve as a valuable therapeutic agent in managing EAM using complete Freund's adjuvant (CFA) induced arthritis during acute and sub-acute phases. Arthritis was induced using intra-dermal administration of CFA in the right hind paw of mice on day 1. Dexamethasone (Dexa) (5 mg/kg/day/animal) was used as a standard treatment. Animals in Dexa and Bacillus subtilis concurrent treatment (BS-CT) received treatments on day 1. The Bacillus subtilis pre-treatment (BS-PT) group received a probiotic dose 7 days before arthritis induction. Parameters like body weight, relative organ weight, colon length, hematology, serum biochemistry, antioxidant capacity, and histopathology of liver, kidney, spleen, colon, stress-related behavioral changes, and cortisol levels were evaluated on days 7 (acute) and 14 (sub-acute). Dexa failed to manage the EAM in arthritic mice and instead exacerbated them. On the other hand, B. subtilis NMCC-path-14 significantly declined EAM with no notable side effects, highlighting its safety and effectiveness. The current data show that B. subtilis NMCC-path-14 may be an alternative option for arthritis treatment that can reduce systemic symptoms associated with arthritis. More studies are required to comprehend the underlying mechanisms of mitigating the EAM by B. subtilis NMCC-path-14.
Insights
Bacillus subtilis NMCC-path-14 effectively managed rheumatoid arthritis extra-articular manifestations in mice, unlike dexamethasone. This probiotic offers a safe and potentially alternative treatment for systemic arthritis symptoms.
Area of Science:
- Microbiology
- Immunology
- Pharmacology
Background:
- Extra-articular manifestations (EAM) significantly impact rheumatoid arthritis (RA) patient quality of life and survival.
- Current treatments for RA and associated EAM often have limitations or adverse effects.
Purpose of the Study:
- To evaluate Bacillus subtilis NMCC-path-14 as a therapeutic agent for managing EAM in a collagen-induced arthritis mouse model.
- To compare the efficacy of Bacillus subtilis NMCC-path-14 with dexamethasone in treating acute and sub-acute phases of arthritis and EAM.
Main Methods:
- Arthritis was induced using complete Freund's adjuvant (CFA) in mice.
- Mice received Bacillus subtilis NMCC-path-14 either concurrently with CFA or as a pre-treatment, alongside a dexamethasone control group.
- Evaluated parameters included body weight, organ weight, colon length, hematology, serum biochemistry, antioxidant capacity, histopathology, and stress markers.
Main Results:
- Dexamethasone exacerbated EAM in arthritic mice.
- Bacillus subtilis NMCC-path-14 significantly reduced EAM without notable side effects, demonstrating safety and efficacy.
- The probiotic treatment improved various physiological and biochemical markers associated with arthritis.
Conclusions:
- Bacillus subtilis NMCC-path-14 shows promise as a safe and effective alternative therapeutic agent for rheumatoid arthritis, particularly for managing systemic extra-articular manifestations.
- Further research is warranted to elucidate the precise mechanisms by which Bacillus subtilis NMCC-path-14 mitigates EAM.

