Effects Of Sodium Butyrate On Alleviating Intestinal Injury In Weaned Piglets Exposed To Deoxynivalenol

Deoxynivalenol(DON)was one of the most pervasive contaminated mycotoxins present in feed all over the world.After animals ingested DON-contaminated feed,they had some symptoms,such as loss of appetite,reduced feed intake,decreased body weight,vomiting,diarrhea and even death,which brought great harm to the breeding industry in my country.Among domestic animals,piglets were the most sensitive to DON and the loss of pig production caused by DON was particularly prominent.The intestine was the primary target organ.Therefore,it’s of great significance to explore the mechanism of DON-induced intestinal injury in piglets and the feasibility of nutritional regulation.Butyric acid was a short-chain fatty acid produced by gut microbiota.Studies had shown that butyric acid can enhance the intestinal barrier function and improve the structure of the gut microbiota,thereby promoting intestinal health.Therefore,this study explored the mitigation effect and biological mechanism of sodium butyrate(SB)on the intestinal injury of weaned piglets exposed to DON through a feeding experiment,which had important theoretical significance and practical value for guiding the prevention and control of the toxic effects of DON and promoting the healthy development of the pig industry.This experiment took 28 piglets weaned at 28 days as the research object,adopted a2×2 factorial experimental design(the main factors are DON and SB),randomly divided into four treatment groups:(1)Control,basal diet;(2)DON,4 mg/kg DON diet;(3)SB,basal diet supplemented with 0.2% SB;(4)DON+SB,4 mg/kg DON diet supplemented with 0.2% SB.The experiment lasted for 4 weeks.Blood samples were collected and piglets were weighed on the 14 th and 28 th day.At the end of the experiment,all piglets were sacrificed and samples were collected.The main results were as follows:1 Effects of SB on growth performance of weaned piglets exposed to DON4 mg/kg DON exposure significantly reduced piglet body weight on the 28 th day(P<0.05)and retarded average daily gain(P<0.05)during the 15-28 d and 1-28 d period.Meanwhile,DON exposure significantly decreased the average daily feed intake during the1-14 d,15-28 d and 1-28 d period(P<0.05).However,the supplement of 0.2% SB significantly increased the body weight on the 14 th and 28 th day(P<0.05),the average daily gain and average daily feed intake during 1-14 d,15-28 d and 1-28 d period(P<0.05).In conclusion,dietary SB could alleviate the growth inhibition caused by DON in piglets.2 Effects of SB on intestinal barrier of weaned piglets exposed to DON4 mg/kg DON exposure resulted in intestinal villi atrophy,fusion,diffuse apical necrosis,and significantly decreased the villus height and villus height to crypt depth ratio of duodenum,jejunum,and ileum(P<0.05),increased the crypt depth of duodenum and jejunum(P<0.05).However,the dietary SB alleviated the small intestinal morphology and pathology caused by DON.DON exposure significantly increased the serum endotoxin content of piglets on the 14 th and 28 th day(P<0.05)and the serum diamine oxidase content on the 28 th day(P<0.05).However,the supplement of 0.2% SB significantly decreased the serum diamine oxidase content on the 14 th and 28 th days(P<0.05).In addition,DON exposure significantly down-regulated the m RNA expression of tight junction protein ZO-1 in the jejunum(P<0.05)and Occludin in the colon(P<0.05),tended to reduce ZO-1m RNA expression in the colon(0.05<P<0.1).However,dietary SB could alleviate the down-regulation of tight junction protein expression exposed to DON,and a significant increase of the Claudin-4 m RNA expression in the jejunum was observed compared to DON group(P<0.05).In conclusion,dietary SB could alleviate intestinal barrier damage caused by DON in piglets.3 Effects of SB on liver function of weaned piglets exposed to DON4 mg/kg DON exposure changed the hepatic histopathology of weaned piglets,causing hepatocyte vacuolar degeneration and focal necrosis.The supplement of 0.2% SB alleviated these pathological changes caused by DON.Besides,DON exposure significantly elevated the activity of serum ALP and AST on the 28 th day(P<0.05).The supplement of 0.2% SB made the activity of serum ALP and AST not significantly different between the DON+SB group and the control group(P>0.05).In addition,SB significantly increased the content of TP on the 14 th and 28 th days(P<0.05).In addition,DON exposure significantly up-regulated the m RNA expression of IL-1β in the liver(P<0.05),while dietary SB significantly down-regulated the expression of IL-1β(P<0.05).No significant differences were observed of the m RNA level of IL-6 and TNF-α among groups(P>0.05).In conclusion,dietary SB could alleviate liver injury caused by DON in piglets.4 Effects of SB on gut microbiota structure and metabolism of weaned piglets exposed to DONNo significant differences on the Chao1,Ace,Shannon,and Simpson indexes of the cecum and colon were observed among the groups(P>0.05).NMDS analyses showed that there was a significant difference in the composition of the cecum(P<0.05),but no significant difference in the composition of the colon(P>0.05).The phyla level of the cecal microbiota: Firmicutes and Bacteroides were the dominant phyla,and there were no significant differences among the various groups(P>0.05).The cecal family level: DON exposure significantly increased the relative abundance of Muribaculaceae,unclassified＿p＿＿Firmicutes,and Family＿XIII(P<0.05).SB decreased the relative abundance of Lactobacillaceae(P<0.05),and tended to reduce Muribaculaceae(0.05<P<0.1).The cecal genus level: DON exposure increased(P<0.05)the abundance of seven genera: norank＿f＿＿Muribaculaceae,unclassified＿p＿＿Firmicutes,Coprococcus＿1,Lachnospira,norank＿f＿＿Eggerthellaceae,Ruminococcaceae＿NK4A214＿group,Ruminococcaceae＿UCG-013 and significantly decreased the relative abundance of Terrisporobacter(P<0.05).In addition,the relative abundance of Lactobacillus,Solobacterium,Ruminococcaceae＿UCG-013 were significantly reduced(P<0.05)and the relative abundance of norank＿f＿＿Muribaculaceae was tended to reduce(0.05<P<0.1)by dietary SB.Besides,the colonic microbiota at phyla level was similar to cecal microbiota.The colonic family level: DON exposure tended to increase the relative abundance of Muribaculaceae(0.05<P<0.1),while dietary SB significantly reduced the relative abundance of Lactobacillaceae,Muribaculaceae and Enterobacteriaceae(P<0.05).The colonic genus level: DON exposure significantly increased the relative abundance of Lachnospiraceae＿UCG-001(P<0.05),and tended to increase the relative abundance of norank＿f＿＿Muribaculaceae(0.05<P<0.1).However,SB significantly decreased the relative abundance of five genera(P<0.05): Lactobacillus,norank＿f＿＿Muribaculaceae,Lachnospiraceae＿UCG-001,Escherichia-Shigella and Family＿XIII＿UCG-001.In addition,SB significantly increased the relative abundance of Prevotella＿2(P<0.05).Dietary DON and SB had no significant difference in the composition of SCFAs in the cecal chyme(P>0.05).However,DON exposure significantly reduced the content of acetic acid and total SCFAs of colonic chyme(P<0.05),and significantly increased the content of isovaleric acid and BCFAs(P<0.05).Dietary 0.2% SB could alleviate the decreased content of acetic acid and total SCFAs caused by DON.In conclusion,dietary sodium butyrate could alleviate the adverse effects of DON on gut microbiota structure and metabolism of piglets.5 Effects of SB on appetite regulation of weaned piglets exposed to DON4 mg/kg DON exposure significantly enhanced the serum PYY content of weaned piglets on the 14 th day(P<0.05),and tended to increase the serum PYY and GLP-1 content on the 28 th day(0.05<P<0.1).The serum PYY content was significantly decreased on the28 th day by SB(P<0.05).What’s more,DON exposure significantly up-regulated the protein expression of the anorectic peptide POMC(P<0.05)and down-regulated the protein expression of the orectic peptide NPY(P<0.05)in the hypothalamus,while dietary SB significantly down-regulated the protein expression of POMC(P<0.05).In conclusion,SB could regulate the gastrointestinal hormones and hypothalamic appetite-related neuropeptides,thereby alleviating the anorexia response caused by DON.In summary,this study drew the following conclusions:(1)DON exposure caused growth performance inhibition,intestinal injury and liver injury of weaned piglets.The addition of SB had a significant alleviative effect on the adverse effects caused by DON.(2)The mechanism might be: SB increased the expression of tight junction proteins and enhanced the barrier function of the intestine;meanwhile improved the structure and metabolism of the cecum and colon microbiota,reduced the relative abundance of harmful bacteria norank＿f＿＿Muribaculaceae and Escherichia-Shigella,and increased the relative abundance of the beneficial bacteria Prevotella-2,which was beneficial to intestinal health,thereby alleviating the intestinal injury caused by DON;in addition,SB regulated the expression of gastrointestinal hormones and hypothalamic appetite-related neuropeptides to stimulate appetite,thus relieved the growth performance decline caused by DON.Therefore,diet supplemented with SB had a great application prospect for preventing and controlling the harmful effect of DON in feed.