Intestinal mucus affinity and biological activity of an orally administered antibacterial and anti-inflammatory peptide
Intestinal mucus affinity and biological activity of an orally administered antibacterial and anti-inflammatory peptide
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DOI：
10.1136/gutjnl-2014-307150
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发表时间：
2015-02-01
期刊：
影响因子：
24.5
通讯作者：
Hornef, Mathias W.
中科院分区：
文献类型：
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作者：
Dupont, Aline;Kaconis, Yani;Hornef, Mathias W.
目的抗菌肽(AMP)对病原微生物的感染具有保护作用，通过抑制上皮细胞表面细菌的生长来维持粘膜内环境的稳定。此外，它们还具有显著的抗炎活性。本文从细菌感染和宿主-微生物平衡的角度分析了口服AMP的解剖分布和生物活性。设计通过免疫染色、功能活性和刺激试验分析了内源性AMP隐蛋白2和合成肽Pep19-2.5在肠粘膜表面的解剖分布和抗菌抗炎活性。Entrica SV.鼠伤寒沙门氏菌模型及比较微生物区系分析。结果发现内源性隐蛋白2附着在肠道粘液层内的微生物区系中。同样，合成肽Pep19-2.5能迅速附着在细菌细胞上，在体内对肠道粘液层表现出显著的亲和力，改变了粘液基质中内毒素的结构组织，并显示出强大的抗炎和抗菌活性。通过高通量16S rDNA测序确定，口服Pep19-2.5可引起肠道微生物区系组成的显著变化。结论合成AMP Pep19-2.5具有抗炎活性和粘液亲和力，并表征了口服AMP Pep19-2.5对微生物区系组成和肠道病原体感染的影响。
Objective Antimicrobial peptides (AMP) provide protection from infection by pathogenic microorganisms and restrict bacterial growth at epithelial surfaces to maintain mucosal homeostasis. In addition, they exert a significant anti-inflammatory activity. Here we analysed the anatomical distribution and biological activity of an orally administered AMP in the context of bacterial infection and host-microbial homeostasis.Design The anatomical distribution as well as antibacterial and anti-inflammatory activity of the endogenous AMP cryptdin 2 and the synthetic peptide Pep19-2.5 at the enteric mucosal surface were analysed by immunostaining, functional viability and stimulation assays, an oral Salmonella enterica subsp. enterica sv. Typhimurium (S. Typhimurium) model and comparative microbiota analysis.Results Endogenous cryptdin 2 was found attached to bacteria of the enteric microbiota within the intestinal mucus layer. Similarly, the synthetic peptide Pep19-2.5 attached rapidly to bacterial cells, exhibited a marked affinity for the intestinal mucus layer in vivo, altered the structural organisation of endotoxin in a mucus matrix and demonstrated potent anti-inflammatory and antibacterial activity. Oral Pep19-2.5 administration induced significant changes in the composition of the enteric microbiota as determined by high-throughput 16S rDNA sequencing. This may have contributed to the only transient improvement of the clinical symptoms after oral infection with S. Typhimurium.Conclusions Our findings demonstrate the antiinflammatory activity and mucus affinity of the synthetic AMP Pep19-2.5 and characterise the influence on microbiota composition and enteropathogen infection after oral administration.