Modulation of gut propionate and intestinal mucosal protection by Bifidobacterium longum: Mitigating methotrexate side effects without compromising the efficacy of psoriasis therapy.

Abstract

Methotrexate (MTX) is a widely used medication that can also be employed in the treatment of psoriasis. Previous studies have emphasized that MTX can induce dysbiosis of the gut microbiota, leading to intestinal damage. In this study, the serum levels of calprotectin and zonulin were elevated in patients treated with MTX, while no significant increase in patients treated with MTX combined with probiotics. Furthermore, we established an imiquimod (IMQ) induced psoriasis-like dermatitis mouse model and treated it with MTX (50 µL, 0.3 mg/mL) and B. longum (200 µL, 1 × 1011 CFU/mL). The results showed that B. longum treatment reduced FITC-dextran intestinal permeability and lowered serum levels of calprotectin and zonulin. It also decreased the expression and secretion levels of inflammatory factors in intestinal tissues, such as IL-6, TNF-α, and IL-23A, while increasing the expression and secretion of the protective factor IL-10. Moreover, B. longum treatment maintained barrier integrity by increasing the abundance of propionate in the gut, thereby regulating the balance of Th17/Treg cells. In conclusion, this study suggests that incorporating B. longum into the traditional MTX regimen may enhance its effectiveness in treating psoriasis while preserving the integrity of the intestinal mucosa.