title: High therapeutic efficacy of Cathelicidin-WA against postweaning diarrhea via inhibiting inflammation and enhancing epithelial barrier in the intestine.
abstract: 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.
authors.affiliation: Institute of Feed Science, College of Animal Science, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Yi
authors.affiliation: Institute of Feed Science, College of Animal Science, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute of Feed Science, College of Animal Science, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, China.
authors.forename: Zhenshun
authors.initials: Z
authors.lastname: Gan
authors.affiliation: Institute of Feed Science, College of Animal Science, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Xiong
authors.affiliation: Institute of Feed Science, College of Animal Science, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, China.
authors.forename: Caihua
authors.initials: C
authors.lastname: Yu
authors.affiliation: Institute of Feed Science, College of Animal Science, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, China.
authors.forename: Huahua
authors.initials: H
authors.lastname: Du
authors.affiliation: Institute of Feed Science, College of Animal Science, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, China.
authors.forename: Yizhen
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D054804:Cathelicidins / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D003967:Diarrhea / Q000188:drug therapy / Q000662:veterinary*; D007249:Inflammation / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology; D007422:Intestines / Q000187:drug effects* / Q000382:microbiology; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D064307:Microbiota / Q000187:drug effects; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D013552:Swine; D013553:Swine Diseases / Q000188:drug therapy*; D014886:Weaning
chemical_list: D054804:Cathelicidins; D016207:Cytokines