title: Butyrate upregulates endogenous host defense peptides to enhance disease resistance in piglets via histone deacetylase inhibition.
abstract: Butyrate has been used to treat different inflammatory disease with positive outcomes, the mechanisms by which butyrate exerts its anti-inflammatory effects remain largely undefined. Here we proposed a new mechanism that butyrate manipulate endogenous host defense peptides (HDPs) which contributes to the elimination of Escherichia coli O157:H7, and thus affects the alleviation of inflammation. An experiment in piglets treated with butyrate (0.2% of diets) 2 days before E. coli O157:H7 challenge was designed to investigate porcine HDP expression, inflammation and E. coli O157:H7 load in feces. The mechanisms underlying butyrate-induced HDP gene expression and the antibacterial activity and bacterial clearance of macrophage 3D4/2 cells in vitro were examined. Butyrate treatment (i) alleviated the clinical symptoms of E. coli O157:H7-induced hemolytic uremic syndrome (HUS) and the severity of intestinal inflammation; (ii) reduced the E. coli O157:H7 load in feces; (iii) significantly upregulated multiple, but not all, HDPs in vitro and in vivo via histone deacetylase (HDAC) inhibition; and (iv) enhanced the antibacterial activity and bacterial clearance of 3D4/2 cells. Our findings indicate that butyrate enhances disease resistance, promotes the clearance of E. coli O157:H7, and alleviates the clinical symptoms of HUS and inflammation, partially, by affecting HDP expression via HDAC inhibition.
authors.affiliation: Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, P.R. China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Xiong
authors.affiliation: Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, P.R. China.
authors.forename: Bingxiu
authors.initials: B
authors.lastname: Guo
authors.affiliation: Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, P.R. China.
authors.forename: Zhenshun
authors.initials: Z
authors.lastname: Gan
authors.affiliation: Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, P.R. China.
authors.forename: Deguang
authors.initials: D
authors.lastname: Song
authors.affiliation: Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, P.R. China.
authors.forename: Zeqing
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, P.R. China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Yi
authors.affiliation: Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, P.R. China.
authors.forename: Yueming
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, P.R. China.
authors.forename: Yizhen
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, P.R. China.
authors.forename: Huahua
authors.initials: H
authors.lastname: Du
mesh_terms: D000818:Animals; D020148:Butyric Acid / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D003092:Colitis / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology; D003106:Colon / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000097:blood; D023082:Defensins / Q000235:genetics* / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D004927:Escherichia coli Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D019453:Escherichia coli O157 / Q000276:immunology*; D005243:Feces / Q000382:microbiology; D015870:Gene Expression; D006463:Hemolytic-Uremic Syndrome / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006655:Histone Deacetylases / Q000378:metabolism; D034421:Sus scrofa; D015533:Transcriptional Activation; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016207:Cytokines; D023082:Defensins; D056572:Histone Deacetylase Inhibitors; D020148:Butyric Acid; D006655:Histone Deacetylases