Risks Related to High-Dosage Recombinant Antimicrobial Peptide Microcin J25 in Mice Model: Intestinal Microbiota,
Haitao Yu1,2, Lijun Shang1,2, Xiangfang Zeng1,2
1State Key Laboratory of Animal Nutrition, Ministry of Agriculture Feed Industry Centre , China Agricultural University , Beijing 100193 , People's Republic of China.
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.
Insights
Recombinant antimicrobial peptide microcin J25 (MccJ25) showed safety benefits at middle dosages in mice, improving gut health. High dosages, however, posed risks, indicating a need for careful MccJ25 administration.
Area of Science:
- Microbiology
- Toxicology
- Gastroenterology
Background:
- Antimicrobial peptides (AMPs) offer potential applications but require thorough safety assessments.
- Microcin J25 (MccJ25) is a promising AMP, necessitating an understanding of its toxicity profile.
Purpose of the Study:
- To evaluate the toxicity risks and safety threshold of orally administered recombinant microcin J25 (MccJ25) in a mouse model.
- To investigate the impact of MccJ25 on intestinal barrier function, gut microbiota, and host physiology.
Main Methods:
- Mice were orally administered varying dosages of MccJ25 (4.55, 9.1, and 18.2 mg/kg) for one week.
- Assessment included body weight, mucosal morphology, intestinal permeability, gut barrier integrity, fecal microbiota composition, and short-chain fatty acid levels.
Main Results:
- Middle-dosage MccJ25 (9.1 mg/kg) administration led to reduced inflammation, improved body weight, enhanced mucosal morphology, and a tighter intestinal barrier.
- Fecal analysis revealed increased Bifidobacterium, decreased coliform bacteria, and elevated short-chain fatty acids in mice receiving middle or low MccJ25 dosages.
- High-dosage MccJ25 administration unexpectedly increased intestinal permeability and induced gut bacterial imbalance.
Conclusions:
- A safe dosage threshold for MccJ25 administration was identified, with middle dosages demonstrating beneficial effects on gut health.
- High MccJ25 dosages present toxicity risks, highlighting the importance of dose-dependent safety evaluations for clinical and food applications.
- These findings support the safe integration of MccJ25 as a food preservative and therapeutic agent.
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