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
IntroductionOmega-3 polyunsaturated fatty acids (n3-PUFA) are known for their anti-inflammatory benefits, particularly in chronic conditions like rheumatoid arthritis (RA). To resolve an acute inflammation, conversion of n3-PUFA into specialized pro-resolving mediators (SPM) is crucial. Recently, it...
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Frontiers Media S.A.
2025-05-01
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| author | Annette Zehrer Alexandra Rausch Paul M. Jordan Oliver Werz Heike Tom Dieck Thomas Berngruber |
| author_facet | Annette Zehrer Alexandra Rausch Paul M. Jordan Oliver Werz Heike Tom Dieck Thomas Berngruber |
| author_sort | Annette Zehrer |
| collection | DOAJ |
| description | IntroductionOmega-3 polyunsaturated fatty acids (n3-PUFA) are known for their anti-inflammatory benefits, particularly in chronic conditions like rheumatoid arthritis (RA). To resolve an acute inflammation, conversion of n3-PUFA into specialized pro-resolving mediators (SPM) is crucial. Recently, it was shown that the probiotic Bacillus megaterium DSM32963 supports this conversion.MethodsThis 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.ResultsOur 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.ConclusionIn conclusion, the specific synbiotic formulation shows promise as a complementary nutritional therapy for RA, improving disease outcomes and modulating immune responses. |
| format | Article |
| id | doaj-art-d1b691629e5a4d43900ff2f91bdd1627 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-d1b691629e5a4d43900ff2f91bdd16272025-08-20T03:47:49ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-05-011610.3389/fimmu.2025.15408781540878Enhancing tofacitinib’s therapeutic efficacy in murine arthritis with a synbiotic formulation comprising Bacillus megaterium DSM 32963 and an Omega-3 fatty acid lysine saltAnnette Zehrer0Alexandra Rausch1Paul M. Jordan2Oliver Werz3Heike Tom Dieck4Thomas Berngruber5Business Unit Microbiotica, Weber & Weber GmbH, Inning, GermanyTHR Cross Indication Research, NUVISAN ICB GmbH, Berlin, GermanyDepartment of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller University Jena, Jena, GermanyDepartment of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller University Jena, Jena, GermanyCreavis, Evonik Operations GmbH, Hanau, GermanyCreavis, Evonik Operations GmbH, Hanau, GermanyIntroductionOmega-3 polyunsaturated fatty acids (n3-PUFA) are known for their anti-inflammatory benefits, particularly in chronic conditions like rheumatoid arthritis (RA). To resolve an acute inflammation, conversion of n3-PUFA into specialized pro-resolving mediators (SPM) is crucial. Recently, it was shown that the probiotic Bacillus megaterium DSM32963 supports this conversion.MethodsThis 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.ResultsOur 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.ConclusionIn conclusion, the specific synbiotic formulation shows promise as a complementary nutritional therapy for RA, improving disease outcomes and modulating immune responses.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1540878/fullprobioticSPMn3-PUFAsynbioticrheumatoid arthritisnutritional supplement |
| spellingShingle | Annette Zehrer Alexandra Rausch Paul M. Jordan Oliver Werz Heike Tom Dieck Thomas Berngruber 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 Frontiers in Immunology probiotic SPM n3-PUFA synbiotic rheumatoid arthritis nutritional supplement |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | probiotic SPM n3-PUFA synbiotic rheumatoid arthritis nutritional supplement |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1540878/full |
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