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 shortchain 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.

Therapeutic administration of the recombinant antimicrobial peptide microcin J25 effectively enhances host defenses against gut inflammation and epithelial barrier injury induced by enterotoxigenic Escherichia coli infection

“…44,45 In this study, we also found that ETEC K88 infection raises the TNF-α, IL-6, and IL-8 secretion and expression in jejunum, ileum, and colon. 8,30 In in vivo experiments, MccJ25 dietary supplements in the form of feed additives for pigs, as well as oral administration of MccJ25, can decrease E. coli numbers in feces. Many published reports have shown that peptides can control harmful inflammation and are ideal candidates for treating acute infections and intestinal tract conditions.…”

“…The group size and doses of MccJ25 and gentamicin were calculated based on our previous study 30 and FDA guidelines, respectively. Gentamicin has been accepted as a first-line choice for treating infections due to E. coli.…”

“…At days 1 and 3 after ETEC K88 infection, mice were either mock-treated or treated with 9.1 mg/kg of body weight (BW) MccJ25 or 10 mg/kg of BW gentamicin in the same manner. The group size and doses of MccJ25 and gentamicin were calculated based on our previous study 30 and FDA guidelines, respectively.…”

“…8,30 Nevertheless, in contrast to bacteriocins and microcin-producing bacteria, we hypothesize that MccJ25 utilization in vivo, as a targeted strategy to treat enterobacterial infection, remains largely understudied. Pretreating intestinal cells with MccJ25 prevented ETEC K88-induced intestinal damage, reduced inflammation, and did not cause in vitro or in vivo cytotoxicity.…”

Dietary supplementation of recombinant antimicrobial peptide Epinephelus lanceolatus piscidin improves growth performance and immune response in Gallus gallus domesticus

“…Additionally, birds fed with AMP-A3 diet had increased villus height of the duodenum, jejunum and ileum [41]. Several articles have suggested that the beneficial effects of oral AMP administration on animal gut morphology could be due to reductions in the population of harmful bacteria [41,42]. In our study, we found that 1.5% rEP significantly increased the numbers of Lactobacillaceae and Entercoccaceae, while decreasing the numbers of Enterobacteriaceae and Staphylococcaceae in duodenum when compared to spiraline A and basal diet groups (S3e Fig). Other studies have shown that administration of AMPs can also significantly decrease pathogens, such as Salmonella, in mice and turkeys [42,43].…”