Lacticaseibacillus Strains Shape Intestinal Immune Homeostasis by Promoting Antimicrobial Activity and Modulating...

Probiotics enhance intestinal defense through immune modulation, barrier reinforcement, and the induction of endogenous antimicrobial proteins. Understanding how specific strains coordinate these mechanisms is essential for their rational application in biomedical and functional food contexts.We investigated whether oral administration of Lacticaseibacillus casei CRL 431 and Lacticaseibacillus paracasei CNCM I-1518 promotes endogenous antimicrobial peptide production and shapes mucosal immune responses. Using a murine supplementation model, we evaluated epithelial barrier integrity, Goblet and Paneth cell responses, cytokine profiles, and the antimicrobial activity of intestinal fluids. In parallel, in vitro assays examined the effects of soluble intestinal factors from probiotic-fed mice on immune cell chemotaxis, antigen-presenting cell maturation, and macrophage survival under oxidative stress.Both probiotic strains increased Goblet cell numbers and tight junction protein expression without altering paracellular permeability. Notably, intestinal fluids from probiotic-fed mice exhibited robust antimicrobial activity associated with Paneth cell activation and enhanced production of enteric α-defensin 5. In addition, probiotic supplementation induced a balanced immune response, characterized by increased pro-inflammatory cytokines (IL-6, IFN-γ, TNF-α) together with IL-10. Importantly, soluble factors from probiotic-fed mice promoted macrophage and T cell chemotaxis, enhanced antigen-presenting cell maturation and cytokine secretion, and improved macrophages survival under oxidative stress.These findings indicate that these probiotic strains induce intestinal changes by integrating antimicrobial peptide production with immune modulation. By demonstrating that probiotic consumption enhances endogenous antimicrobial activity and soluble factor-mediated immune modulation, this study provides mechanistic insights relevant to probiotic-based strategies aimed at strengthening mucosal defenses and limiting pathogen colonization.