Microbe-Derived Antimicrobial Peptides: Immunomodulation and Gut Microbiota Homeostasis.

Antimicrobial peptides (AMPs) are key components of the innate immune system across a wide range of organisms. In addition to their direct antimicrobial activity, AMPs exert immunomodulatory effects that differ from those of conventional antibiotics. This review summarizes recent evidence on the roles of microbe-derived AMPs in regulating immune cell function, including neutrophil activation and NET formation, macrophage polarization, and lymphocyte proliferation and differentiation. It also examines their organ-specific roles, particularly in intestinal immunity through reinforcement of the intestinal barrier, maintenance of gut microbiota homeostasis, and promotion of sIgA secretion. Together, their direct antimicrobial and immunomodulatory activities support the therapeutic potential of microbe-derived AMPs against drug-resistant infections, cancer, and inflammatory conditions. We synthesize recent evidence on the modulation of innate and adaptive immunity by microbe-derived AMPs. This review provides an integrated framework for understanding how microbe-derived AMPs orchestrate immune defense across cellular, tissue, and systemic levels, with implications for therapeutic development against infectious, inflammatory, and neoplastic diseases.