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

Abstract

Recombinant antimicrobial peptide microcin J25 (MccJ25) causes potent antimicrobial activity against enterotoxigenic Escherichia coli (ETEC) in vitro; however, independently of this activity, its role in suppressing intestinal inflammation and epithelial barrier injury in vivo remains unclear. We investigated the therapeutic effects of MccJ25 on intestinal inflammation and epithelial barrier dysfunction and the underlying mechanism, using gentamicin for comparison. In a mouse model of intestinal inflammation, therapeutic administration of either MccJ25 or gentamicin after ETEC K88 infection attenuated clinical symptoms, reduced intestinal pathogen colonization, improved intestinal morphology, and decreased inflammatory pathologies and intestinal permeability, ultimately improving the hosts' health. MccJ25 also attenuated ETEC-induced mouse intestinal barrier dysfunction by enhancing tight junction proteins (TJPs). Using the human epithelial cell line Caco-2, we verified the epithelial barrier-strengthening and mucosal injury-alleviating effects of MccJ25 on ETEC infection: increased expression of TJPs by activating the p38/MAPK pathway, balancing the microbiota, and improving short-chain fatty acid concentrations in the cecum of ETEC-infected mice. Although gentamicin and MccJ25 had similar effects in the inflamed gut, MccJ25 was superior to gentamicin with regard to defending the host from ETEC infection. Overall, MccJ25 may be a promising therapeutic drug for treating enteric pathogen-induced intestinal inflammation diseases. K E Y W O R D S gut microbiota, inflamed gut, inflammation diseases, intestinal barrier injury, mice, pathogens infection | 1019 YU et al.

Administration of Saccharomyces boulardii mafic-1701 improves feed conversion ratio, promotes antioxidant capacity, alleviates intestinal inflammation and modulates gut microbiota in weaned piglets

“…Thus, we speculate that S. boulardii ma c-1701 altered the level of pro-in ammatory cytokines through modulation of the signaling pathway involved in inhibition of nuclear factor kappa B activated pathways. In addition, other previous studies have reported that mucus is composed of many immunomodulatory molecules with mucins forming the basic skeleton, which protect intestinal epithelial barrier integrity and reduce proin ammatory responses [4,30]. Caballero-Franco et al demonstrated that oral administration of probiotic increased mucin gene expression and secretion [31].…”

“…The concentrations of SCFAs were assayed as literature reported [4,15]. Brie y, approximately 0.5 g of intestinal digesta was weighed into a 10 mL polypropylene tube and diluted 1:16 with ultrapure water (8 mL).…”

“…Weaning is the most stressful period in pig's life [1]. Some non-antibiotic solutions, including antimicrobial peptides, prebiotics, anti-virulence molecules, antibodies and probiotics, have been developed to maintain the health status of newly weaned piglets [2][3][4].…”

Administration of Saccharomyces boulardii mafic-1701 improves growth performance, promotes antioxidant capacity, alleviates intestinal inflammation and modulates gut microbiota in weaned piglets

“…It is generally known that the deleterious effects of weaning on the piglets gastrointestinal are vast, although the mechanisms by weaning influences intestinal function are less clear, it is certain that weaning could lead to drastic changes in breakdown of intestinal barrier functions [22]. The intestinal barrier is composed of intestinal epithelium cells and the tight junction proteins of epithelial cells [4].…”

“…To relieve weaning stress, traditional antibiotics have been used markedly in recent decade. While, considering the intensifying substantial environmental pollution, arise antimicrobial resistance and global public health crisis, several replacements have been developed over the past years, including antimicrobial peptides, prebiotics, new antibiotics, anti-virulence molecules, antibodies and probiotics [4].…”