Probiotics, including Lacticaseibacillus rhamnosus (L. rhamnosus), have gained recognition for their potential health benefits, such as enhancing immune function, maintaining gut health, and improving nutrient absorption. This study investigated the effectiveness of L. rhamnosus LM1019 (LM1019) in enhancing immune function. In RAW 264.7 cells, LM1019 demonstrated dose-dependent immune stimulation by increasing nitric oxide production, gene expression of proinflammatory cytokines, and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). These effects were mediated through the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) translocation without inducing cytotoxicity. Furthermore, orally administered LM1019 was evaluated in immunosuppressed mice induced by cyclophosphamide (CTX). High-dose administration of LM1019 significantly increased the subpopulations of lymphocytes, specifically helper T cells (CD4⁺), as well as two subtypes of natural killer (NK) cells, namely, IFN-γ⁺ and granzyme B⁺ NK cells. Additionally, LM1019 at a high dose led to elevated levels of proinflammatory cytokines, including IFN-γ and IL-12, compared to CTX-treated mice. These findings highlight the potential of LM1019 in enhancing the immune system. The study contributes to the growing body of research on the beneficial effects of probiotics on immune function.

Probiotics offer a non-pharmacological approach to support immune function, yet clinical evidence for strain-specific benefits remains limited. We conducted an 8-week, randomized, double-blind, placebo-controlled trial of Lacticaseibacillus rhamnosus LM1019 in 121 generally healthy adults. Both the active and placebo arms produced comparable within-group increases in natural killer (NK) cell cytotoxicity and modest, non-differential declines in circulating cytokines; safety and tolerability were excellent, with mild adverse events evenly distributed. In a post-hoc subgroup defined by age ≥ 40 years, baseline white blood cell count ≥ 5.0 × 10³/µL, and LDL cholesterol < 130 mg/dL, the probiotic arm demonstrated statistically significant enhancements in NK activity (p = 0.021–0.008 across all effector-to-target ratios), whereas no change was observed in the placebo group. These findings suggest that this intervention may selectively boost NK-mediated immunity in individuals with preserved baseline immune and lipid profiles. Future larger trials using phenotype-driven enrollment and controlled dietary intake are warranted to confirm and extend these results.