Risks Related to High-Dosage Recombinant Antimicrobial Peptide Microcin J25 in Mice Model: Intestinal Microbiota, Intestinal Barrier Function, and Immune Regulation.

Abstract

Antimicrobial peptide (AMP) can be a promising alternative in various domains. However, further risk information is required. In this study, mice were orally administrated different dosages of recombinant AMP microcin J25 (4.55, 9.1, and 18.2 mg/kg; MccJ25) for 1 week, and the toxicity risk impacts were examined. We evidenced that middle-dosage administration mice had a lower inflammation, better body weight, and ameliorated mucosal morphology, accompanied by reduced intestinal permeability and tighter intestinal barrier. Fecal microbiota composition analysis in middle- or low-dosage mice revealed the Bifidobacterium count was increased and the coliform bacteria count was decreased, and increased in short-chain fatty acid levels. Unexpectedly, there was a risk that high-dosage mice increased intestinal permeability and imbalance of intestinal bacteria. Taken together, these data indicated a safe threshold for usage of MccJ25 in clinical practice. Such studies can effectively enhance the safety of various aspects such as food preservative and drug.