Immunoprotective effects of Lacticaseibacillus casei OS1423 against transient immunosuppression via enhancement of host immunity and gut microbiota modulation

Probiotics are increasingly recognized for their ability to modulate immune responses, but strain-specific efficacy and safety remain critical for their application. This study aimed to identify immunomodulatory probiotics that can protect against transient immunosuppression. A total of 931 probiotic strains were screened for nitric oxide induction in macrophages, with 196 candidates selected. Through assessments of oxygen and heat tolerance, gastrointestinal survivability, cytokine production, four strains; Lacticaseibacillus casei OS1423, L. paracasei OS1213, Limosilactobacillus fermentum SLfe039, and Bifidobacterium longum SBLO386, were selected. These strains demonstrated a rigorous safety profile in compliance with international regulatory standards, confirmed by the absence of antibiotic resistance genes, hemolytic activity, and cytotoxicity. In a cyclophosphamide (CP)-induced immunosuppressed mouse model, OS1423 exhibited the most potent immune-protective effects. OS1423 administration effectively mitigated weight loss, preserved splenic cell numbers, restored natural killer (NK) cell activity, and promoted T/B cell proliferation. Serum immunoglobulin levels (IgA and IgG) and cytokine expression in splenocytes and colon tissues were significantly protected from CP treatment. Microbiome analysis revealed that OS1423 pre-administration mitigated gut dysbiosis induced by CP, suppressing inflammatory-associated genera ( Ruminococcus and Alistipes ) and maintaining beneficial taxa such as Anaeroplasma , which correlated with immune markers. This comprehensive evaluation across in vitro , ex vivo , and in vivo platforms demonstrates that OS1423 exerts robust immunoprotective effects through modulation of host immune responses and gut microbiota composition. These findings support its potential use as a functional food ingredient or therapeutic adjunct to support immune health under transient immunosuppressive conditions.