A Novel Cecropin-LL37 Hybrid Peptide Protects Mice Against EHEC Infection-Mediated Changes in Gut Microbiota, Intestinal Inflammation, and Impairment of Mucosal Barrier Functions

Abstract

Intestinal inflammation can cause impaired epithelial barrier function and disrupt immune homeostasis, which increases the risks of developing many highly fatal diseases. Enterohemorrhagic Escherichia coli (EHEC) O157:H7 causes intestinal infections worldwide and is a major pathogen that induces intestinal inflammation. Various antibacterial peptides have been described as having the potential to suppress and treat pathogen-induced intestinal inflammation. Cecropin A (1-8)-LL37 (17-30) (C-L), a novel hybrid peptide designed in our laboratory that combines the active center of C with the core functional region of L, shows superior antibacterial properties and minimized cytotoxicity compared to its parental peptides. Herein, to examine whether C-L could inhibit pathogen-induced intestinal inflammation, we investigated the anti-inflammatory effects of C-L in EHEC O157:H7-infected mice. C-L treatment improved the microbiota composition and microbial community balance in mouse intestines. The hybrid peptide exhibited improved anti-inflammatory effects than did the antibiotic, enrofloxacin. Hybrid peptide treated infected mice demonstrated reduced clinical signs of inflammation, reduced weight loss, reduced expression of pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interferon-gamma (IFN-γ)], reduced apoptosis, and reduced markers of jejunal epithelial barrier function. The peptide also affected the MyD88-nuclear factor κB signaling pathway, thereby modulating inflammatory responses upon EHEC stimulation. Collectively, these findings suggest that the novel hybrid peptide C-L could be developed into a new anti-inflammatory agent for use in animals or humans.

Time-course alterations of gut microbiota and short-chain fatty acids after short-term lincomycin exposure in young swine

“…The results in accordance with expectation was that the restraint of well-recognized pathogenic bacteria Terrisporobacter [42], Lachnoclostridium [43,44], Clostridium_sensu_stricto_1 [33,45], Clostridium_sensu_stricto_6 [46] and unknown functional bacteria norank_f__Oscillospiraceae, unclassi ed_f__Prevotellaceae, etc. were notably observed after short-term lincomycin treated.…”

Oral Administration of Nanopeptide CMCS-20H Conspicuously Boosts Immunity and Precautionary Effect Against Bacterial Infection in Fish

“…Intestinal microorganisms form a symbiotic ecosystem, which helps maintain the steady balance in intestine and is essential to the health of humans and animals ( 14 , 55 ). It is reported that intestinal inflammation will lead to changes in intestinal microorganisms, thus affecting the normal function of organisms ( 56 ).…”

“…The immunomodulatory activity of AMPs mostly depends on its influence on the function of innate immune cells and mediators ( 12 ). In addition, AMPs (such as lactoferrin, polypeptide S100, LL-37, cecropin A) have the advantages of broad-spectrum antibacterial activity, small bioconcentration, and less possibility to cause bacterial resistance ( 13 , 14 ). Therefore, the researches on immune enhancement of AMPs have also become a hotspot in recent years.…”

A Novel Nano-Antimicrobial Polymer Engineered with Chitosan Nanoparticles and Bioactive Peptides as Promising Food Biopreservative Effective against Foodborne Pathogen E. coli O157-Caused Epithelial Barrier Dysfunction and Inflammatory Responses

“…Importantly, enterohemorrhagic Escherichia coli (EHEC) O157, a critical foodborne pathogen, infection is a major enteric pathogenic disease and primary cause of food contamination, diarrhea and death in humans, neonates and weaned animals. In addition, food spoilage caused by pathogenic microorganisms is also a cause of foodborne illness, which raises significant health concerns [5][6][7][8]. Antibiotic therapy has been used to control intestinal diseases for many years, but antibiotic resistance has rapidly emerged worldwide [9][10][11][12].…”