High therapeutic efficacy of Cathelicidin-WA against postweaning diarrhea via inhibiting inflammation and enhancing epithelial barrier in the intestine.
High therapeutic efficacy of Cathelicidin-WA against postweaning diarrhea via inhibiting inflammation and enhancing epithelial barrier in the intestine.
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Cathelicidin-WA 通过抑制炎症和增强肠道上皮屏障对断奶后腹泻具有高效治疗作用
DOI：
10.1038/srep25679
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发表时间：
2016-05-16
影响因子：
4.6
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Yi H;Zhang L;Gan Z;Xiong H;Yu C;Du H;Wang Y
腹泻是幼年哺乳动物死亡的主要原因，特别是在断奶期间。在此，我们研究了放线菌素-Wa(CWA)对幼年哺乳动物断奶期间腹泻、肠道形态、炎症反应、上皮屏障和微生物区系的影响。选取临床腹泻仔猪，分别给予生理盐水(对照组)、环孢素A(CWA)和恩诺沙星(Enro)治疗4d。CWA和Enro均能有效缓解腹泻。与对照组相比，CWA可降低空肠IL-6、IL-8和IL-22水平，减少中性粒细胞进入空肠。CWA通过下调TLR4、MyD88和NF-κB依赖的途径来抑制炎症。此外，CWA通过增加绒毛和微绒毛的高度来改善肠道形态，并通过增加紧密连接(TJ)蛋白的表达和增强肠道上皮细胞的伤口愈合能力来增强肠道屏障功能。CWA还改善了微生物区系组成，增加了粪便中的短链脂肪酸(SCFA)水平。相比之下，Enro不仅破坏了肠道屏障，还对肠道微生物区系组成和SCFA水平产生了负面影响。总之，CWA有效地减轻了炎症，增强了肠道屏障功能，并改善了断奶仔猪肠道中的微生物区系组成。这些结果表明，CWA对幼年哺乳动物的腹泻或其他肠道疾病可能是一种有效而安全的治疗方法。
Diarrhea is a leading cause of death among young mammals, especially during weaning. Here, we investigated the effects of Cathelicidin-WA (CWA) on diarrhea, intestinal morphology, inflammatory responses, epithelial barrier and microbiota in the intestine of young mammals during weaning. Piglets with clinical diarrhea were selected and treated with saline (control), CWA or enrofloxacin (Enro) for 4 days. Both CWA and Enro effectively attenuated diarrhea. Compared with the control, CWA decreased IL-6, IL-8 and IL-22 levels and reduced neutrophil infiltration into the jejunum. CWA inhibited inflammation by down-regulating the TLR4-, MyD88- and NF-κB-dependent pathways. Additionally, CWA improved intestinal morphology by increasing villus and microvillus heights and enhancing intestinal barrier function by increasing tight junction (TJ) protein expression and augmenting wound-healing ability in intestinal epithelial cells. CWA also improved microbiota composition and increased short-chain fatty acid (SCFA) levels in feces. By contrast, Enro not only disrupted the intestinal barrier but also negatively affected microbiota composition and SCFA levels in the intestine. In conclusion, CWA effectively attenuated inflammation, enhanced intestinal barrier function, and improved microbiota composition in the intestines of weaned piglets. These results suggest that CWA could be an effective and safe therapy for diarrhea or other intestinal diseases in young mammals.