Background/Purpose: Rheumatoid arthritis (RA), affecting approximately 1% of the global population RA is a leading cause of disability worldwide. Despite available treatments, including methotrexate (MTX) and biologics, many patients fail to achieve lasting remission. RA is associated with intestinal dysbiosis and increased intestinal permeability, two features that associate with local and systemic inflammation in RA. Certain probiotic strains have been shown to benefit patients with RA by reducing disease activity scores, indirect measures of increased intestinal permeability, and some pro-inflammatory measures. These observations highlight the potential of probiotics as a complementary approach for managing inflammation in RA.To support RA management, we developed SBD121, a synbiotic medical food composed of plant-derived probiotics and prebiotic fibers. This study aimed to evaluate the preclinical efficacy of SBD121 in reducing RA severity, alone and in combination with MTX, as well as to explore its mechanisms of action in vitro.

Methods: We examined SBD121 in a collagen-induced arthritis (CIA) mouse model. Mice received SBD121 (1×1010 colony forming units) or a water control via oral gavage twice daily for 42 days. Arthritis was induced 28 days after SBD121 initiation, followed by injection with MTX (5 mg/kg) or a vehicle control 3 times weekly. Joint swelling and clinical scores were assessed on days 18, 24, 28, 31, and 35. To dissect SBD121’s cellular effects in vitro, human intestinal epithelial cells and immune cells were exposed to SBD121. Barrier integrity (transepithelial electrical resistance), cytokine production (ELISA), and transcriptional responses (RT-qPCR) were measured.

Results: SBD121, co-administered with MTX, significantly reduced RA clinical scores relative to MTX + vehicle in a CIA mouse model. SBD121 alone did not affect clinical score relative to the CIA control. In vitro, SBD121 improved intestinal barrier integrity without inducing inflammatory cytokine secretion; an effect associated with reduced systemic inflammation. SBD121 also reduced Th17-associated immune cell responses (IL-23, IL-6, IL-8, and CXCL1 secretion).

Conclusion: Here, we have demonstrated that SBD121 potentiates the effects of MTX in a CIA model of RA. Our in vitro results suggest that this synergy may be due to attenuated Th17 responses and/or improved intestinal barrier function. Ongoing studies aim to elucidate SBD121’s specific effects on articular cells and determine the role of MTX in SBD121-influenced responses. The efficacy of SBD121 in combination with MTX in newly diagnosed RA patients is being evaluated in an ongoing double-blind placebo-controlled clinical trial (NCT06005220).

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/dietary-management-of-rheumatoid-arthritis-a-functional-investigation-of-the-synbiotic-medical-food-sbd121/