Akkermansia muciniphila and Lactobacillus plantarum ameliorate systemic lupus erythematosus by possibly regulating immune response and remodeling gut microbiota

Abstract

ABSTRACT Systemic lupus erythematosus (SLE), characterized by persistent inflammation, is a complex autoimmune disorder that affects all organs, challenging clinical treatment. Dysbiosis of gut microbiota promotes autoimmune disorders that damage extraintestinal organs. Modulating the gut microbiome is proposed as a promising approach for fine-running parts of the immune system, relieving systematic inflammation in multiple diseases. This study demonstrated that the administration of Akkermansia muciniphila and Lactobacillus plantarum contributed to an anti-inflammatory environment by decreasing IL-6 and IL-17 and increasing IL-10 levels in the circulation. The treatment of A. muciniphila and L. plantarum restored the intestinal barrier integrity to a different extent. In addition, both strains reduced the deposit of IgG in the kidney and improved renal function significantly. Further studies revealed distinct remodeling roles of A. muciniphila and L. plantarum administration on the gut microbiome. This work demonstrated essential mechanisms of how A. muciniphila and L. plantarum remodel gut microbiota and regulate the immune responses in the SLE mice model. IMPORTANCE Several pieces of research have demonstrated that certain probiotic strains contribute to regulating excessive inflammation and restoring tolerances in the SLE animal model. More animal trials combined with clinical studies are urgently needed to further elucidate the mechanisms for the effect of specific probiotic bacteria in preventing SLE symptoms and developing novel therapeutic targets. In this study, we explored the role of A. muciniphila and L . plantarum in ameliorating the SLE disease activity. Both A. muciniphila and L. plantarum treatment relieved the systemic inflammation and improved renal function in the SLE mouse model. We demonstrated that A. muciniphila and L. plantarum contributed to an anti-inflammatory environment by regulating cytokine levels in the circulation, restoring the intestinal barrier integrity, and remodeling the gut microbiome, however, to a different extent.