Abstract

Rheumatoid arthritis (RA) is linked to gut barrier dysfunction and microbiota dysbiosis. We developed an oral Spirulina platensis -based hydrogel (SP-gel) with favorable physicochemical properties (gastric retention-intestinal sustained release). In vitro , SP-gel restored intestinal barrier integrity and alleviated inflammation. In vivo , oral SP-gel (especially combined with intra-articular hyaluronic acid) ameliorated joint inflammation, bone erosion, and cartilage degradation in collagen-induced arthritis mice. Mechanistically, SP-gel reinforced the gut barrier, rebalanced immunity (regulatory T/t helper 17 cells) and remodeled gut microbiota. It also showed good biosafety and enhanced methotrexate efficacy. Our findings highlight SP-gel’s potential as a safe oral adjuvant therapy for RA targeting the gut–joint axis.