Immune Microenvironment-Dependent Effects of Age-Associated Bifidobacterium Strains on Gut Immunity and Microbial Diversity

Yaqin He¹Furui Zhang²Zhiqiang Tian¹Wen Jun¹Ming Su¹Liping Hong¹Ruyi Zhang¹Cao Zhang^3*Jinhai Tian^1*Le Guo^1*

• ¹General Hospital of Ningxia Medical University, Yinchuan, China
• ²Ningxia Medical University, Yinchuan, China
• ³General Hospital of Ningxia Medical University Department of Gastroenterology, Yinchuan, China

Despite extensive research on probiotics, how age-associated Bifidobacteria strains modulate gut immunity and microbial diversity remains unclear. 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. 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.