Immune microenvironment-dependent effects of age-associated Bifidobacterium strains on gut immunity and microbial diversity.

Background: The applications of probiotics in food and infant formula are greatly increased. Bifidobacterium, a genus of beneficial bacteria, plays a crucial role in the human gut microbiota. Despite extensive research on probiotics, how age-associated Bifidobacteria strains modulate gut immunity and microbial diversity remains unclear.

Methods: Our present study investigates the immunomodulatory effects of two Bifidobacterium strains, Bifidobacterium adolescentis (BA) and Bifidobacterium longum subsp. infantis (BI), on gut immunity and microbial diversity using three models: a DSS-induced chronic colitis mouse model, germ-free mouse model, and in vitro human intestinal γδ T cell co-culture system.

Results: Transcriptomic analysis in the DSS-induced colitis model revealed differential gene expression, particularly in cytokine signaling pathways and γ-chain-related cytokines crucial for γδ T cell function. Both BA and BI reduced γδ T cell infiltration in colorectal tissues, and modulated immune activation markers, with distinct effects on peripheral blood γδ T cell levels. RNA-seq analysis post-probiotic treatment highlighted strain-specific changes, with BA activating NOD2-like receptor signaling and BI enhancing IL-17 and TNF signaling pathways. Direct co-culture experiments demonstrated BI's robust activation of γδ T cells, while BA showed minimal direct effects. Multi-omics correlation analysis suggested that BA and BI modulated immune responses through microenvironment-dependent mechanisms, offering potential therapeutic insights for gut-related inflammatory diseases.

Conclusions: Our findings provide a theoretical basis for the development of age-associated probiotic intervention strategies, offering new insights into personalized microbiota modulation to enhance immune health and gut homeostasis across different life stages.