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Antimicrobial peptides (AMPs) are a potential class of antimicrobial agents. Here, we have designed the potential oral route for antimicrobial peptide R7I with anti\u2010proteolytic properties to deal with bacterial enteritis in mice. The results revealed that R7I protected the liver and gut from damage caused by inflammation. RNA\u2010Seq analysis indicated that R7I promoted digestion and absorption in the small intestine by upregulating transmembrane transporter activity, lipid and small molecule metabolic processes and other pathways, in addition to upregulating hepatic steroid biosynthesis and fatty acid degradation. For the gut microbiota, <jats:italic>Clostridia<\/jats:italic> were significantly reduced in the R7I\u2010treated group, and <jats:italic>Odoribacteraceae<\/jats:italic>, an efficient isoalloLCA\u2010synthesizing strain, was the main dominant strain, protecting the gut from potential pathogens. 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