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

J Agric Food Chem. 2018 Oct 31;66(43):11301-11310. doi: 10.1021/acs.jafc.8b03405. Epub 2018 Oct 22.

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.

Keywords: BALB/c mic; gut microbiota; intestinal inflammation; intestinal permeability; recombinant microcin J25; toxicity risk.

MeSH terms

  • Animals
  • Bacteriocins / administration & dosage*
  • Bacteriocins / adverse effects
  • Bifidobacterium / isolation & purification
  • Claudin-1 / metabolism
  • Colony Count, Microbial
  • Cytokines / metabolism
  • Fatty Acids, Volatile / metabolism
  • Feces / microbiology
  • Female
  • Gastrointestinal Microbiome / drug effects*
  • Inflammation
  • Intestines / drug effects
  • Intestines / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Occludin / metabolism
  • Permeability
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Toxicity Tests

Substances

  • Bacteriocins
  • Claudin-1
  • Cldn1 protein, mouse
  • Cytokines
  • Fatty Acids, Volatile
  • Occludin
  • Ocln protein, mouse
  • Recombinant Proteins
  • microcin