Lactobacillus gasseri KBL697 ameliorates psoriatic inflammation through the modulation of gut-skin axis

Abstract

Abstract Psoriasis is a chronic inflammatory disease arising from aberrant interactions between various immune cells and cytokines. The current standard therapy includes topical steroids, methotrexate or anti-IL-17A/IL-23 antibodies. However, due to the limited efficacy and associated side effects, there is still an unmet medical need for the development of novel therapeutic agents for this disease. KBL697 is a strain of Lactobacillus gasseri, isolated from the vaginal samples of healthy donors. We previously reported that KBL697 ameliorated the symptoms of an inflammatory bowel disease mouse model. At the molecular level, KBL697 decreased pro-inflammatory cytokines including IFN-gamma, IL-6, and IL-17A, while an anti-inflammatory cytokine IL-10 was increased. In the current study, we tested KBL697 in pre-clinical models for psoriasis. Oral administration of KBL697 showed a significant beneficial effect in imiquimod-induced mouse models, judged by the skin inflammation, PASI score and immune profile change. Further studies revealed that IL-10 is induced by lipoteichoic acid (LTA) of KBL697, indicating the critical role of LTA/IL-10 in the anti-inflammatory function of KBL697. In the skin analysis, key cytokines in psoriasis, such as IL-17A, IL-23, and IL-36, are downregulated while genes for skin regeneration are upregulated, supporting the model for KBL697 working in the gut-skin axis. Therefore, KBL697 has great potential as a novel therapeutic agent for the treatment of psoriasis.