# 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

## TL;DR

A synbiotic combining a probiotic and Omega-3 fatty acid improves arthritis treatment in rats when used with tofacitinib.

## Contribution

A novel synbiotic formulation enhances tofacitinib's efficacy in treating murine arthritis.

## Key findings

- Low-dose tofacitinib with synbiotic improved arthritis severity parameters more than single treatments.
- The synbiotic reduced CRP and markers of NETosis in joint tissue.
- Synbiotic-containing groups showed decreased neutrophil chemokine CXCL1 and trends in lower inflammatory cytokines.

## Abstract

Omega-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.

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.