The mechanism of action of nisin in promoting poultry through tight junction integrity and dendritic cell anti-inflammatory properties.

Antimicrobial resistance in microbes poses a global health threat, making the search for alternatives to antibiotic growth promoters (AGPs) in the livestock industry an urgent priority. Nisin, an antibacterial peptide widely used as a food preservative, can enhance the poultry growth performance. However, its efficacy requires high doses owing to its degradation by digestive enzymes. Moreover, the mechanisms underlying its effect remain unclear. We investigated the effects of nisin on antimicrobial activity, tight junction integrity, and anti-inflammatory response using intestinal microorganisms, epithelial cells, and immune cells. Nisin displayed broad antibacterial activity against Gram-positive bacteria, including both pathogenic and beneficial species such as lactic acid bacteria. In contrast, Gram-negative bacteria, such as Escherichia coli and Salmonella, were highly resistant to nisin. Moreover, nisin improved tight junction integrity at concentrations over 100 times lower than those required for antimicrobial activity. In addition, nisin reduced inflammation-related cytokines, including TNF-α, IL-1β, IL-6, and IL-12p70, secreted by dendritic cells at concentrations over five times lower than those needed for antimicrobial activity. Furthermore, the prototype of the enteric-coated nisin was effective under a state of dynamic equilibrium in the dissolution tests. Notably, nisin improved tight junction integrity at low concentrations, comparable to those of AGPs. Therefore, the results suggest that the growth-promoting effect of nisin is not due to antimicrobial action but rather to its ability to enhance tight junction integrity and reduce inflammation of dendritic cells, making it a potential alternative to AGPs without the risk of superbug emergence.