Application of the Protease-Resistant Antimicrobial Peptide R7I, Composed of Natural Amino Acids, as a Functional Food Ingredient for Modulating Intestinal Health

Foodborne pathogenic bacterial infections pose significant challenges to global food safety and public health, while the issue of antimicrobial resistance (AMR) has worsened in recent years, creating an urgent need for safe, natural alternatives to combat foodborne pathogens and associated intestinal diseases. This study focuses on the Antimicrobial and Protease-resistant Peptide R7I, composed of natural amino acids, elucidating its mechanisms of action as a functional food ingredient in modulating intestinal health, thereby offering novel strategies for antibiotic alternatives. The results showed a 13.52% increase in average daily weight gain in the R7I group compared to the control group. Average daily feed intake was significantly lower (P < 0.05) in the control group than in both the normal and R7I groups. Additionally, serum and jejunal lipopolysaccharide (LPS) content, as well as serum D-lactic acid levels (P < 0.05), were reduced in the R7I group, indicating markedly alleviated intestinal permeability. Compared to the control group, the R7I group significantly reduced serum levels of lactate dehydrogenase and total bile acids, while increasing high-density lipoprotein levels (P < 0.05). R7I treatment significantly elevated (P < 0.05) serum levels of anti-inflammatory cytokines interleukin-4 (IL-4) and interleukin-4 (IL-10), while suppressing production of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-17 (IL-17). Furthermore, multi-omics analyses revealed that R7I alleviated Enterotoxigenic Escherichia coli (ETEC)-induced intestinal damage through synergistic mechanisms involving modulation of gene expression regulatory pathways, restructuring of gut microbiota composition, and improvement of metabolite profiles. These findings substantiate the potential of R7I as a promising antibiotic-alternative functional food ingredient, offering new strategies for preventing foodborne diseases and managing intestinal health.