Two intestinal microbiota-derived metabolites,deoxycholic acid and butyrate,synergize to enhance host defense peptide synthesis and alleviate necrotic enteritis

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外文摘要：Background Necrotic enteritis(NE)is a major enteric disease in poultry,yet effective mitigation strategies remain elusive.Deoxycholic acid(DCA)and butyrate,two major metabolites derived from the intestinal microbiota,have independently been shown to induce host defense peptide(HDP)synthesis.However,the potential synergy between these two compounds remains unexplored.Methods To investigate the possible synergistic effect between DCA and butyrate in regulating HDP synthesis and barrier function,we treated chicken HD11 macrophage cells and jejunal explants with DCA and sodium butyrate(NaB),either individually or in combination,for 24 h.Subsequently,we performed RNA isolation and reverse transcrip-tion-quantitative PCR to analyze HDP genes as well as the major genes associated with barrier function.To further determine the synergy between DCA and NaB in enhancing NE resistance,we conducted two independent trials with Cobb broiler chicks.In each trial,the diet was supplemented with DCA or NaB on the day-of-hatch,followed by NE induction through sequential challenges with Eimeria maxima and Clostridium perfringens on d 10 and 14,respectively.We recorded animal mortality after infection and assessed intestinal lesions on d 17.The impact of DCA and NaB on the microbiota in the ileum and cecum was evaluated through bacterial 16S rRNA gene sequencing.Results We found that the combination of DCA and NaB synergistically induced multiple HDP genes in both chicken HD11 cells and jejunal explants.Additionally,the gene for claudin-1,a major tight junction protein,also exhibited synergistic induction in response to DCA and NaB.Furthermore,dietary supplementation with a combination of 0.75 g/kg DCA and 1 g/kg NaB led to a significant improvement in animal survival and a reduction in intestinal lesions compared to either compound alone in a chicken model of NE.Notably,the cecal microbiota of NE-infected chickens showed a marked decrease in SCFA-producing bacteria such as Bacteroides,Faecalibacterium,and Cuneatibacter,with lactobacilli becoming the most dominant species.However,supplementation with DCA and NaB largely restored the intestinal microbiota to healthy levels.Conclusions DCA synergizes with NaB to induce HDP and claudin-1 expression and enhance NE resistance,with potential for further development as cost-effective antibiotic alternatives.

外文关键词：

Bile acidsHost defense peptidesMetabolitesMicrobiomeNecrotic enteritisShort-chain fatty acids

作者：

Dohyung M.Kim、Jing Liu、Melanie A.Whitmore、Isabel Tobin、Zijun Zhao、Guolong Zhang

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作者单位：

Department of Animal and Food Sciences,Oklahoma State University,Stillwater,OK,USA

基金：

USDA National Institute of Food and Agriculture grantsUSDA National Institute of Food and Agriculture grantsRalph F.and Leila W.Boulware Endowment FundOklahoma Agricultural Experiment Station ProjectUSDA National Institute of Food and Agriculture Predoctoral Fellowship grant

项目编号：

2020-67016-316192023-67015-39095H-31122021-67034-35184

出版年：

2024

DOI：

10.1186/s40104-024-00995-9

畜牧与生物技术杂志(英文版)

中国科学技术协会

畜牧与生物技术杂志(英文版)

CSTPCD

影响因子：0.765

ISSN：1674-9782

年,卷(期)：2024.15(3)