Alleviation Mechanism Of Baicalin On Lincomycin-Induced Intestinal Mucosal Injury In Piglets

The diarrhea of piglets seriously affected the efficient production of pigs.Antibiotics were the most effective treatment for piglet diarrhea.Exploring the effects of therapeutic antibiotic on the intestinal barrier of piglets and how to reduce this negative effect can help to reduce antibiotic use and develop alternative antibiotic strategies.Baicalin has the potential of intestinal protection and damage repair due to its antibacterial,anti-inflammatory and apoptosis promoting activities.In this study,the healing effect of baicalin on intestinal mucosal injury of piglets induced by therapeutic antibiotic exposure and its mechanism were explored by constructing mouse therapeutic antibiotic injury model and carrying out animal experiments in piglets and mice,combined with 16 S rDNA sequencing,RNA-seq and correlation network analysis techniques.The main contents and results are as follows:1.Establish an intestinal injury model induced by lincomycin in mice: 36 21-day-old female ICR mice were randomly divided into 3 groups and fed with lincomycin without(CON)or 1 g/L(LM1)or 5g/L(LM5)in drinking water for one week,respectively,to explore the effect of lincomycin exposure on intestinal barrier.The results showed that 1 g/L lincomycin exposure significantly reduced the body weight gain of the mice(P < 0.05).Both 1 g/L and 5 g/L lincomycin exposure decreased the colonic microbial diversity and composition,and short-chain fatty acid concentration of mice(P < 0.05).Moreover,5 g/L lincomycin exposure destroyed the intestinal morphology of jejunum and ileum in mice,and significantly reduced the villus height and crypt depth of jejunum and ileum and the mRNA expression levels of TLR2,TLR3,TLR4,IL-18,TNF-α and P65 in jejunum of mice(P < 0.05).Therefore,in this study,5 g/L dose was selected to establish a mouse model of lincomycin injury.2.Effects and mechanism of baicalin in repairing intestinal injury caused by lincomycin.21-day-old female ICR mice were randomly divided into three groups: control group(CON),lincomycin exposure group(add with 5 g/L lincomycin in water expose 7 days,contrast treatment for 7 days,LM),baicalin recovery group(add 5 g/L lincomycin in water expose 7 days,and add 500 mg/kg baicalin in feed recovered 7 days,LM + BL),to explore the recovery effects of baicalin on lincomycin-induced intestinal damage.The results revealed that baicalin significantly restored lincomycin-induced weight loss and the decrease of villus height and crypt depth in jejunum(P < 0.05).Also,baicalin restored the relative abundance of Firmicutes,Proteobacteria,Klebsiella and Citrobacter(P < 0.05),and the decrease of the content of isobutyric acid in colonic chyme and the serum levels of inflammatory cytokines IL-1β,IL-6and TNF-α(P < 0.05).In addition,baicalin rescued lincomycin-induced gene expression changes and the mRNA expression of mucin-type O-glycan biosynthesis related genes galnt5,galnt10,galnt17,and core1 synthase(P < 0.05).These results suggest that baicalin may regulate the biosynthesis of mucin-type Oglycan by increasing the expression of core 1 synthase and thereby repairing lincomycin-induced intestinal damage.3.Effects of baicalin on growth performance and intestinal mucosa in piglets exposed to lincomycin.48 piglets weaned at 21-day-old with body weight of 5.41±0.24 kg were randomly divided into three groups: control group(basic fodder,CON),lincomycin exposure group(add 1000 mg/kg lincomycin in feed expose 7 days,basic fodder for 7 days,LM),baicalin recovery group(add 1000 mg/kg lincomycin in feed expose 7 days,add 500 mg/kg baicalin recovered 7 days,LM + BL),to explore the effects of baicalin on growth performance and intestinal mucosa in piglets exposed to lincomycin.The results indicated that baicalin significantly recovered lincomycin-induced weight loss,liver and heart weight loss in weaned piglets,and restored the decrease of Jejunal villus height,colonic muscular thickness and Claudin-1 mRNA expression in colon and reduced intestinal permeability(P < 0.05).In addition,baicalin showed a tendency to restore the decrease of TNF-α mRNA expression and the increase of IL-17 mRNA expression in lincomycin-induced piglets,and reduce intestinal inflammatory response in piglets.In conclusion,these results suggest that baicalin has the ability to restore the decreased growth performance and intestinal barrier damage caused by lincomycin,and the repair mechanism may be related to the biosynthesis of mucin-type O-glycan and the regulation of intestinal microorganisms.