ORIGINAL RESEARCH article

Front. Immunol.

Sec. Nutritional Immunology

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1540878

Enhancing Tofacitinib's Therapeutic Efficacy in Murine Arthritis with a Synbiotic Formulation Comprising Bacillus megaterium DSM 32963 and an Omega-3 Fatty Acid Lysine Salt

Provisionally accepted
  • 1Weber & Weber GmbH - Business Unit Microbiotica, Inning, Germany
  • 2Nuvisan Innovation Campus Berlin (ICB) GmbH, Berlin, Baden-Württemberg, Germany
  • 3Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller University Jena, Jena, Thuringia, Germany
  • 4Evonik Operations GmbH,, Hannu, Germany

The final, formatted version of the article will be published soon.

Omega-3 polyunsaturated fatty acids (n3-PUFAs) are known for their anti-inflammatory benefits, particularly in chronic conditions like rheumatoid arthritis (RA). To resolve an acute inflammation, conversion of n3-PUFAs into specialized pro-resolving mediators (SPM) is crucial. Recently, it was shown that the probiotic Bacillus megaterium DSM32963 supports this conversion. This study evaluates a synbiotic formulation combining Bacillus megaterium DSM32963 and a unique n3-PUFA-lysine salt as adjunct nutritional supplement to tofacitinib in adjuvant-induced arthritis (AIA) in rats.Our findings reveal that a combination of low-dose tofacitinib and the synbiotic (ldTofa+Syn) significantly improved all measured arthritis severity parameters, outperforming either single treatment as well as supplementation with a conventional omega-3 ethyl ester that showed no effects on disease severity. The ldTofa+Syn combination also led to a notable reduction in C-reactive protein (CRP) and markers of NETosis in joint tissue, with a significant decrease in neutrophil chemokine CXCL1 observed only in synbiotic-containing groups. Additionally, there was a marked trend towards lower levels of the key inflammatory cytokines TNFα, IL-1β, and IL-6 in the ldTofa+Syn group.In conclusion, the specific synbiotic formulation shows promise as a complementary nutritional therapy for RA, improving disease outcomes and modulating immune responses.

Keywords: probiotic1, Spm2, n3-PUFA3, Synbiotic4, rheumatoid arthritis5, nutritional supplement6, adjuvant therapy7, Chronic Inflammation8

Received: 06 Dec 2024; Accepted: 30 Apr 2025.

Copyright: © 2025 Zehrer, Rausch, Jordan, Werz, Tom Dieck and Berngruber. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Annette Zehrer, Weber & Weber GmbH - Business Unit Microbiotica, Inning, Germany

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