Bifidobacterium animalis subsp. lactis and Enterococcus hirae Enhance Immunity by Modulating Gut Microbiota and Metabolic Pathways in Immunosuppressed Mice
摘要
Probiotics play a crucial role in regulating host immunity, but the mechanisms underlying their effects along the gut-immune axis remain incompletely understood. This study aims to investigate the effects of Bifidobacterium animalis subsp. lactis MH-02 and Enterococcus hirae 8–62 on immune restoration, gut microbiota composition, and metabolite profiles in cyclophosphamide-induced immunosuppressed mice. Hematological, serological, histological, microbial, and metabolomic analyses were performed to evaluate the impacts of the two probiotic strains. Our findings revealed that both probiotic strains increased immune cell counts, cytokine and antibody levels, and improved spleen and intestinal histology. Particularly, MH-02 increased leukocytes, monocytes, IL-6, and IgA, whereas E. hirae 8–62 elevated IFN-γ. Additionally, MH-02 increased Bacteroidota and Limosilactobacillus and decreased Firmicutes, while E. hirae 8–62 increased Firmicutes, Kineothrix, Eubacterium_R, and Ventrisoma. Both probiotics similarly enhanced the abundance of Muribaculum. Furthermore, MH-02 upregulated serotonin and melatonin via the tryptophan metabolism pathway, whereas E. hirae 8–62 upregulated N-acetyl-aspartic acid and ureidosuccinic acid associated with alanine, aspartate, and glutamate metabolism. Moreover, MH-02-associated taxa were correlated with serotonin, melatonin, and immune markers, and E. hirae 8-62-associated taxa with N-acetyl-aspartic acid, ureidosuccinic acid, and immune markers. This study identifies B. animalis MH-02 and E. hirae 8–62 as candidate probiotics that may support immune modulation by reshaping the gut microbiota and metabolite landscape in immunosuppressed conditions.