Lactiplantibacillus plantarum Lp05 ensures immune developmental safety and protects against colitis via promoting Treg differentiation in mice

ABSTRACT Lactiplantibacillus plantarum (formerly Lactobacillus plantarum ) Lp05, a strain isolated from pickled vegetables, is widely used as a probiotic in the food industry. However, its impact on the host immune system, especially the adaptive immune system, remains poorly understood. In this study, we systematically evaluated the influence of Lp05 on T cell immunity under both homeostatic and inflammatory conditions in mice. First, we showed that early life exposure to Lp05 does not compromise the development or maturation of the adaptive immune system, as evidenced by normal thymic T cell development and unaltered immune cell profiles in the spleen and lymph nodes of offspring from Lp05-treated dams. Second, in an inflammatory setting of an inflammatory bowel disease model, Lp05 supplementation protected mice against dextran sulfate sodium-induced colitis. Mechanistically, this protection was correlated with an increased differentiation of CD4 + Foxp3 + Treg cells, likely associated with enhancement of microbial amino acid biosynthesis and metabolic pathways in the gut. Taken together, our findings demonstrate that Lp05 administration is safe for T cell development and exhibits therapeutic potential in colitis, primarily by promoting Treg cell differentiation. IMPORTANCE Despite the growing use of probiotics in immune-targeted products, their specific effects on adaptive immunity are not well defined. This study systematically evaluates the probiotic strain Lactiplantibacillus plantarum Lp05, examining its influence on T cell immunity during both early-life development and inflammatory disease. We show that perinatal Lp05 exposure does not adversely affect immune development. In a model of inflammatory bowel disease, Lp05 supplementation effectively attenuated dextran sulfate sodium-induced colitis. This protection was associated with a marked increase in intestinal Treg cell differentiation, potentially mediated through enhanced microbial amino acid biosynthesis. Importantly, these findings confirm that a food-origin probiotic can be safely administered during immune development while exerting therapeutic benefits via Treg induction, bridging key gaps between probiotic safety, immune modulation, and clinical potential.