Antimicrobial peptides and proteins as rheostats of intestinal homeostasis and immunity

Antimicrobial peptides and proteins (AMPs) function as molecular rheostats of host-microbe interactions and cell-intrinsic defense. Rather than being binary effectors, they act along a continuum. At basal levels, AMPs maintain harmony with the commensal members of the microbiome, and upon pathogen encounter, they induce levels that thwart bacterial invasion and dissemination. This duality arises from the mechanistic versatility and layered regulation by microbial, cytokine, and circadian cues. Importantly, this review is not intended to be a detailed catalog of all antimicrobial proteins, but rather a conceptual framework highlighting representative mechanisms that illustrate how AMPs function as adjustable regulators of intestinal homeostasis. Viewing AMPs as adjustable regulators of barrier integrity, rather than static effectors, reframes innate immunity as a dynamic system that balances microbial tolerance with host defense.