Abstract: Probiotics have garnered extensive attention for their roles in regulating host metabolism, immune homeostasis, and gut ecological balance; however, the material basis underlying these functions and the prevailing research paradigms continue to evolve. This review summarizes recent progress in probiotic research from two perspectives: material basis and research paradigms. With respect to material basis, it outlines how probiotic surface-associated components (including adhesins, pili, exopolysaccharides, and cell wall microbe-associated molecular patterns) interact with host receptor axes and elucidates their roles in colonization, immunomodulation, and signal transduction. It also summarizes the roles of probiotic-derived metabolites, including short-chain fatty acids, bile acids and their metabolites, vitamins, polyamines, and neuroactive compounds, in regulating host metabolism and signaling pathways. In addition, it discusses how cross-feeding, niche occupation, and colonization resistance contribute to maintaining gut homeostasis. Regarding research paradigms, it reviews and highlights how emerging multimodal methods such as single-cell technologies, multi-omics integration, organ-on-a-chip platforms, humanized animal models, and clinical studies advance functional dissection and causal verification. Finally, in the context of precision nutrition and individualized medicine, it outlines future application directions and research priorities for probiotics.

Key words: probiotics; material basis; host-microbe interactions; multimodal research