The gut microbiota modulates host immunity through a wide array of metabolic products that function as signaling molecules, thereby linking microbial activity with both mucosal and systemic immune responses. Notably, short-chain fatty acids, secondary bile acids, tryptophan-derived indoles, polyamines, and lipid derivatives play pivotal roles in regulating innate and adaptive immune functions via G protein-coupled receptors, nuclear receptors, and epigenetic pathways. These metabolites modulate immune cell differentiation, epithelial barrier integrity, and the resolution of inflammation in a dose- and site-specific manner. Recent advancements in spatial metabolomics, synthetic biology, and nanomedicine have facilitated the spatiotemporal delivery of these immunomodulatory compounds, revealing novel therapeutic avenues for the treatment of inflammatory and autoimmune disorders. This review summarizes the biosynthesis and immunoregulatory functions of key microbial metabolites, highlights the compartmentalized and systemic mechanisms of action, and discusses emerging therapeutic approaches, including postbiotics, engineered probiotics, and receptor-targeting drugs. We also explore the challenges in achieving personalized microbiome-immune modulation and propose future directions integrating multiomics and AI-driven predictive modeling. Understanding the metabolite-immune axis paves the way for novel interventions targeting host-microbe symbiosis.

Antibiotics remain central to modern poultry production, but their long-term and sometimes poorly managed use has markedly altered gut microbial ecology, effectively transforming the intestine into a substantial reservoir of antibiotic resistance genes (ARGs). In poultry, the composition of ARGs reflects not only resistant bacterial taxa but also the activity of mobile genetic elements, shifts in gut metabolic conditions, and features of the surrounding production system. This review synthesizes current understanding of both the structural and functional features of the poultry resistome, with particular attention to key bacterial hosts and the mobile genetic elements they carry. We further evaluate how different antibiotic-use patterns and additional co-selective pressures alter microbial communities and contribute to the persistence of ARGs. We also delineate the major transmission pathways that link breeder flocks, hatcheries, production facilities, and manure management, and interpret these connections within a One Health perspective. Particular emphasis is placed on microbial and nutritional interventions that influence gut microbial interactions, epithelial barrier integrity, and metabolic signaling. Drawing on these findings, we propose a resistome–microbiome–metabolome axis that links microbial taxa, resistance elements, and key metabolic signals, offering a conceptual framework for developing more targeted antimicrobial resistance mitigation strategies in poultry systems.