The interplay between gut microbiota and host immunity is now recognized as a key determinant of intestinal and whole-body homeostasis. Disruption of this delicate balance-often referred to as dysbiosis-has been linked not only to inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), but also to extra-intestinal conditions such as type 2 diabetes mellitus (T2DM) and chronic obstructive pulmonary disease (COPD) 1; 2. This Research Topic, the second volume of our Community Series, brings together seven articles that collectively advance our mechanistic understanding of microbiota-immune interactions and explore novel therapeutic strategies targeting this axis. The collection includes foundational mechanistic reviews, disease-specific applications, and original research that translates mechanistic insights into therapeutic validation.Two comprehensive reviews in this volume provide essential frameworks for understanding how gut microbes influence host immunity. Yu et al. systematically dissect the immunoregulatory roles of microbial metabolites-short-chain fatty acids (SCFAs), tryptophan derivatives, and bile acidshighlighting their ability to influence T cell differentiation, macrophage polarization, and key inflammatory signaling pathways including nuclear factor kappa-B (NF-κB), the NLR family pyrin 33 domain containing 3 inflammasome (NLRP3), and the Janus kinase/signal transducer and activator 34 of transcription (JAK-STAT) pathway 2. this, Wang et al. explore the reciprocal 35 nature of host-microbiota dialogue, emphasizing how the immune system, particularly secretory 36 immunoglobulin A (IgA) T cell subsets, actively sculpts microbial community 37Together, these reviews underscore that maintaining immune homeostasis requires a dynamic 38 equilibrium, in which microbial metabolites serve as critical signaling molecules and the immune 39 system acts as an ecological filter that enforces microbial stability. 40The gut-lung axis has gained substantial traction; Ni et al. extend alginate, and hyaluronic acid formulations-that enable pH/reactive oxygen species (ROS)-74 responsive drug delivery and improve colonic targeting. This integration of traditional bioactive 75 compounds with modern nanotechnology exemplifies a forward-looking strategy for precision 76 intervention. 77The articles in this volume underscore a critical transition in the field: the shift from describing 79
Li et al. (Tue,) studied this question.