The synbiotic mixture of lactulose and Bacillus coagulans protects intestinal barrier dysfunction and apoptosis in weaned piglets challenged with lipopolysaccharideOA

Background Lactulose as an effective prebiotic protects intestinal mucosal injury. Bacillus coagulans is widely used in feed additives because of its ability to promote intestinal health. Our previous study suggests that the combination of lactulose and Bacillus coagulans may be a good candidate as alternative for antibiotic growth promoters. However,the in vivo effects of lactulose and Bacillus coagulans on growth and intestinal health under immune challenge in piglets remains unclear. The obje...     

Dietary supplementation of zinc oxide modulates intestinal functionality during the post-weaning period in clinically healthy pigletsOA

Background To improve our understanding of host and intestinal microbiome interaction, this research investigated the effects of a high-level zinc oxide in the diet as model intervention on the intestinal microbiome and small intestinal functionality in clinically healthy post-weaning piglets. In study 1, piglets received either a high concentration of zinc(Zn) as zinc oxide(Zn O, Zn, 2,690 mg/kg) or a low Zn concentration(100 mg/kg) in the diet during the post weaning period(d 14–23). The effec...     

Enterococcus faecium NCIMB 10415 administration improves the intestinal health and immunity in neonatal piglets infected by enterotoxigenic Escherichia coli K88

Background: This study aimed to investigate the effects of oral administration of Enterococcus faecium NCIMB10415(E. faecium) on intestinal development, immunological parameters and gut microbiota of neonatal piglets challenged with enterotoxigenic Escherichia coli K88(ETEC). A total of 96 1-day-old sow-reared piglets were randomly assigned to 2 groups, with 48 piglets in each group. The piglets were from 16 litters(6 piglets each litter),and 3 piglets each litter were allocated to the E. faecium-supplemented(PRO) group, while the other 3 piglets were allocated to the control(CON) group. After colostrum intake, piglets in the PRO group were orally administrated with 3 × 10~9 CFU E. faecium per day for a period of one week. On day 8, one piglet per litter from each group was challenged(CON+ETEC, PRO+ETEC) or not(CON-ETEC, PRO-ETEC) with ETEC in a 2 × 2 factorial arrangement of treatments. On day 10(2 days after challenge), blood and tissue samples were obtained from piglets.Results: Before ETEC challenge, there were no significant differences for the average daily gain(ADG) and fecal score between the two groups of piglets. After ETEC challenge, the challenged piglets had greater fecal score compared to the non-challenged piglets, whereas E. faecium administration was able to decrease the fecal score.Piglets challenged with ETEC had shorter villous height, deeper crypt depth, and reduced number of goblet cells in the jejunum and decreased m RNA abundance of claudin-1 in the ileum, whereas increased the percentage of lymphocytes, concentrations of IL-1β in the plasma and TNF-α in the ileal mucosa, as well as increased the m RNA abundances of innate immunity-related genes in the ileum tissue. These deleterious effects caused by ETEC were partly alleviated by feeding E. faecium. In addition, piglets in PRO-ETEC group had decreased the percentage of CD8~+T cells of the peripheral blood when compared to those in CON-ETEC group. Moreover, E. faecium administration increased Verrucomicrobia at phylum level and decreased Bilophila at genus level.Conclusions: These results suggest that oral administration of E. faecium alleviated the intestinal injury and diarrhea severity of neonatal piglets challenged by ETEC, partly through improving the intestinal microbiota and immune response. This offers a potential strategy of dietary intervention against intestinal impairment by ETEC in neonatal piglets.     

Myokine interleukin-15 expression profile is different in suckling and weaning piglets

Interleukin-15(IL-15) is a cytokine highly expressed in skeletal muscle. The objective of the present study was to investigate the development of muscle IL-15 expression in suckling piglets and in early weaning piglets(day 14) at each level, that is, mRNA, protein, and secretion. Eight litters(eight piglets per litter) of newborn healthy piglets(Large × White × Landrace) with a similar initial weight(1618.0 ± 140.1 g) were chosen and divided into two groups, Group one used suckling piglets that were killed, respectively, at days 1,7,14,21, and group two used early(day 14) weaning piglets that were killed respectively, at days 15, 17, 19, 21. In group one, IL-15 gene expression levels increased significantly(P 0.05) along with increased body weight over time. IL-15 protein expression levels in piglets at day 21 of age were higher(P 0.05) than those in piglets at other ages, and there was no difference(P 0.05)among piglets at other ages. These findings indicated that increased IL-15 mRNA expression did not result in a corresponding increase of its protein expression. In group two, which used early weaning piglets from days 15-19, IL-15 mRNA and protein expression levels increased constantly(P 0.05) and were higher(P 0.05) than those in suckling piglets. Moreover, there was no gain of body weight(P 0.05) compared with suckling piglets at day 14 of age. However, IL-15 protein expression levels in early weaning piglets at day 21 of age dropped significantly(P 0.05) to the levels as suckling piglets at day 21 of age, while body weight increased(P 0.05) markedly to the levels as suckling piglets at day 21 of age. In both groups, the serum IL-15 levels of piglets decreased significantly(P 0.01) over time. Taken together, our results indicate that IL-15 expression differs in suckling piglets and in weaning piglets. It is speculated that IL-15 may play an important role in counteracting the effects of early weaning stress.     

Mechanisms Involved in the Growth Promotion of Weaned Piglets by High-level Zinc Oxide1

Dietary supplementation with high lev- els of zinc oxide （ZnO） is an effective method to prevent diarrhea and promote growth in weaned pig- lets. However, the mechanisms behind these beneficial effects are not well understood. Recent advances in this field indicated that the effects of ZnO on piglet growth are achieved through multiple regulatory path- ways rather than a single pathway. This review focu- ses on recent advances in the effects of high level ZnO on： 1 ） Zn status in weaned piglets; 2 ） intestinal microbe flora regulation; 3 ） intestinal structure and function;4） ion secretion in the intestine epithelium;5） intestinal immunology; and 6） secretion of brain-in- testine peptides. ZnO appears to regulate the intestinal microflora and decreases the release of histamine to prevent diarrhea. ZnO also increases the expression of intestinal insulin-like growth factor-1 （ IGF-1 ） and the IGF-1 receptor to ameliorate intestinal injury associat- ed with weaning, and mediates secretion of brain-gut peptides to stimulate food intake, to promote the growth of piglets. Better understanding of the underly-1 ing mechanisms should inspire us to supplement the diet for weaned piglets with ZnO and investigate new approaches to prevent diarrhea and enhance growth.     

Galacto-oligosaccharides improve barrier function and relieve colonic inflammation via modulating mucosa-associated microbiota composition in lipopolysaccharides-challenged piglets

Background:Galacto-oligosaccharides(GOS)have been shown to modulate the intestinal microbiota of suckling piglets to exert beneficial effects on intestinal function.However,the modulation of intestinal microbiota and intestinal function by GOS in intestinal inflammation injury models has rarely been reported.In this study,we investigated the effects of GOS on the colonic mucosal microbiota composition,barrier function and inflammatory response of lipopolysaccharides(LPS)-challenged suckling piglets.Methods:A total of 18 newborn suckling piglets were divided into three groups,the CON group,the LPS-CON group and the LPS-GOS group.Piglets in the LPS-GOS group were orally fed with 1 g/kg body weight of GOS solution every day.On the d 14,piglets in the LPS-CON and LPS-GOS group were challenged intraperitoneally with LPS solution.All piglets were slaughtered 2 h after intraperitoneal injection and sampled.Results:We found that the colonic mucosa of LPS-challenged piglets was significantly injured and shedding,while the colonic mucosa of the LPS-GOS group piglets maintained its structure.Moreover,GOS significantly reduced the concentration of malondialdehyde(MDA)and the activity of reactive oxygen species(ROS)in the LPS-challenged suckling piglets,and significantly increased the activity of total antioxidant capacity(T-AOC).GOS significantly increased the relative abundance of norank_f_Muribaculaceae and Romboutsia,and significantly decreased the relative abundance of Alloprevotella,Campylobacter and Helicobacter in the colonic mucosa of LPS-challenged suckling piglets.In addition,GOS increased the concentrations of acetate,butyrate and total short chain fatty acids(SCFAs)in the colonic digesta of LPS-challenged suckling piglets.GOS significantly reduced the concentrations of interleukin 1β(IL-1β),interleukin 6(IL-6),tumor necrosis factor-α(TNF-α)and cluster of differentiation 14(CD14),and the relative mRNA expression of Toll-like receptor 4(TLR4)and myeloid differentiation primary response 88(MyD88)in the LPS-challenged suckling piglets.In addition,GOS significantly reduced the relative mRNA expression of mucin2(MUC2),and significantly increased the protein expression of Claudin-1 and zonula occluden-1(ZO-1)in LPS-challenged suckling piglets.Conclusions:These results suggested that GOS can modulate the colonic mucosa-associated microbiota composition and improve the intestinal function of LPS-challenged suckling piglets.     

Alterations in intestinal microbiota composition coincide with impaired intestinal morphology and dysfunctional ileal immune response in growing-finishing pigs under constant chronic heat stressOA

Background: Previous studies had shown that short-term acute heat stress(HS) affected the host’s metabolism and intestinal microbiota independent of feed intake(FI) reduction, and long-term calorie restriction caused intestinal morphological injuries and gut microbial alterations. However, research on the effects of constant chronic HS on intestinal microbial composition and the roles of FI reduction played in is limited. This study aimed to investigate the effects of 7-day constant chronic HS o...     

N-Acetyl-D-glucosamine improves the intestinal development and nutrient absorption of weaned piglets via regulating the activity of intestinal stem cells

Early weaning in piglets can cause a series of negative effects.This causes serious losses to the livestock industry.N-Acetyl-D-glucosamine(D-GlcNAc)plays an important role in regulating the homeostasis of the intestine.This study aimed to investigate the effects of D-GlcNAc on the growth performance and intestinal function of weaned piglets.Twenty-four weaned piglets([Yorkshire×Landrace]
Duroc,6.58±0.15 kg,n=8)at 21 d old were fed 3 diets supplemented with 0(control),1 and 3 g/kg D-GlcNAc.The intestinal organoid model was used to verify the regulatory mechanism of D-GlcNAc on intestinal epithelial cells.On the whole,supplementation of D-GlcNAc in the piglet diet has no significant effect on the growth performance and diarrhoea of weaned piglets(P>0.05).The apparent digestibility of nutrients and mRNA abundance of nutrient transporters in the 1 g/kg D-GlcNAc group were increased significantly(P<0.05).D-GlcNAc did not affect villus height(VH)and crypt depth(CD)but resulted in a numerically shorter VH and shallower CD,which lead to an increase in ileal VH:CD ratio(P<0.05).Cell shedding rates in the ileum villi increased(P<0.05).The relative length and weight of the small intestine of weaned piglets increased(P<0.05).In vitro studies found that the budding rates of organoids treated with 0.1 mmol/L D-GlcNAc increased on the d 3 and 5(P<0.05).The average budding numbers per budding organoid treated with 0.1 and 10 mmol/L D-GlcNAc increased on d 3(P<0.05).D-GlcNAc upregulated leucine rich repeat containing G protein-coupled receptor 5(Lgr5⁺)and Chromogranin A mRNA abundance in organoids(P<0.05).Mucin 2(Muc2)expression increased when treated with 1 and 10 mmol/L D-GlcNAc(P<0.05).In conclusion,dietary D-GlcNAc cannot improve the growth performance of weaned piglets.However,it can promote the growth and development of the intestinal tract and improve the digestion and absorption capacity of the intestine,which is achieved by affecting the activity of intestinal stem cells.     

Dietary protocatechuic acid ameliorates inflammation and up-regulates intestinal tight junction proteins by modulating gut microbiota in LPS-challenged piglets

Background: Weaning is one of the major factors that cause stress and intestinal disease in piglets. Protocatechuic acid(PCA) is an active plant phenolic acid which exists in Chinese herb, Duzhong(Eucommia ulmoides Oliver), and is also considered as the main bioactive metabolite of polyphenol against oxidative stress and inflammation. This study aimed to investigate the effect of PCA on growth performance, intestinal barrier function, and gut microbiota in a weaned piglet model challenged with lipopolysaccharide(LPS).Methods: Thirty-six piglets(Pig Improvement Company line 337 × C48, 28 d of age, 8.87 kg ± 0.11 kg BW) were randomly allocated into 3 treatments and fed with a basal diet(CTL), a diet added 50 mg/kg of aureomycin(AUR), or a diet supplemented with 4000 mg/kg of PCA, respectively. The piglets were challenged with LPS(10 μg/kg BW) on d 14 and d 21 by intraperitoneal injection during the 21-d experiment. Animals(n = 6 from each group) were sacrificed after being anesthetized by sodium pentobarbital at 2 h after the last injection of LPS. The serum was collected for antioxidant indices and inflammatory cytokines analysis, the ileum was harvested for detecting mRNA and protein levels of tight junction proteins by PCR and immunohistochemical staining, and the cecum chyme was collected for intestinal flora analysis using 16 S rRNA gene sequencing.Results: Dietary supplementation of PCA or AUR significantly increased the expression of tight junction proteins including ZO-1 and claudin-1 in intestinal mucosa, and decreased the serum levels of thiobarbituric acid reactive substances(TBARS) and IL-6, as compared with CTL group. In addition, PCA also decreased the serum levels of IL-2 and TNF-α(P < 0.05). Analysis of gut microbiota indicated that PCA increased the Firmicutes/Bacteroidetes ratio(P < 0.05). Spearman's correlation analysis at the genus level revealed that PCA reduced the relative abundance of Prevotella 9, Prevotella 2, Holdemanella, and Ruminococcus torques group(P < 0.05), and increased the relative abundance of Roseburia and Desulfovibrio(P < 0.05), whereas AUR had no significant effect on these bacteria.Conclusions: These results demonstrated that both PCA and AUR had protective effect on oxidative stress, inflammation and intestinal barrier function in piglets challenged with LPS, and PCA potentially exerted the protective function by modulating intestinal flora in a way different from AUR.     

L. reuteri ZJ617 inhibits inflammatory and autophagy signaling pathways in gut-liver axis in piglet induced by lipopolysaccharideOA

Background: This study investigated the protective effects of L. reuteri ZJ617 on intestinal and liver injury and the underlying mechanisms in modulating inflammatory, autophagy, and apoptosis signaling pathways in a piglet challenged with lipopolysaccharide(LPS).Methods: Duroc × Landrace × Large White piglets were assigned to 3 groups(n = 6/group): control(CON) and LPS groups received oral phosphate-buffered saline for 2 weeks before intraperitoneal injection(i.p.) of physiological saline or LP...     

Microencapsulated essential oils combined with organic acids improves immune antioxidant capacity and intestinal barrier function as well as modulates the hindgut microbial community in pigletsOA

Background: The objective of this experiment was to evaluate the effect of a combination of microencapsulated essential oils and organic acids(MOA) on growth performance, immuno-antioxidant status, intestinal barrier function and microbial structure of the hindgut in piglets. A total of 120 piglets(Duroc × [Landrace × Yorkshire];weighted 7.66 ± 1.79 kg, weaned at d 28) were randomly selected and allocated to 3 treatments with 4 replicates per group and 10 piglets per replicate according to the i...     

Effects of lactic acid bacteria-fermented formula milk supplementation on ileal microbiota,transcriptomic profile,and mucosal immunity in weaned pigletsOA

Background:Lactic acid bacteria(LAB) participating in milk fermentation naturally release and enrich the fermented dairy product with a broad range of bioactive metabolites,which has numerous roles in the intestinal health-promoting of the consumer.However,information is lacking regarding the application prospect of LAB fermented milk in the animal industry.This study investigated the effects of lactic acid bacteria-fermented formula milk(LFM) on the growth performance,intestinal immunity,microb...     

Effect of sialyllactose on growth performance and intestinal epithelium functions in weaned pigs challenged by enterotoxigenic Escherichia ColiOA

Background: Sialyllactose(SL) is one of the most abundant oligosaccharides present in porcine breast milk.However, little is known about its effect on growth performance and intestinal health in weaned pigs. This study was conducted to explore the protective effect of SL on intestinal epithelium in weaned pigs upon enterotoxigenic Escherichia coli(ETEC) challenge.Methods: Thirty-two pigs were randomly divided into four treatments. Pigs fed with a basal diet or basal diet containing SL(5.0 g/kg) ...     

Effects of galacto-oligosaccharides on growth and gut function of newborn suckling piglets

Background: Most research on galacto-oligosaccharides(GOS) has mainly focused on their prebiotic effects on the hindgut,but their beneficial effects on the small intestine(SI) have received little attention.Since jejunum is the important place to digest and absorb nutrients efficiently,optimal maturation of the jejunum is necessary for maintaining the high growth rate in the neonate.Therefore,this study investigates the effect of the early intervention with GOS on the intestinal development of the jejunum.Methods: A total of 6 litters of neonatal piglets(10 piglets per litter; Duroc × Landrace × Large White) with an average birth weight of 1.55 ± 0.05 kg received 1 of 2 treatments based on their assignment to either the control(CON) group or the GOS(GOS) group in each litter.Piglets in the GOS group were orally administrated 10 mL of a GOS solution(reaching 1 g GOS/kg body weight) per day from the age of 1 to 7 d; the piglets in the CON group were treated with the same dose of physiological saline.All piglets were weaned on d 21.On d 8 and 21 of the experimental trial,1 pig per group from each of the 6 litters was euthanized.Results: The early intervention with GOS increased the average daily gains in the third week(P 0.05).Decreased crypt depth was also observed in the jejunum of the piglets on d 21(P 0.05).The early intervention with GOS increased the jejunal lactase activity on d 8,maltase activity and sucrase activity on d 21(P 0.05).In addition,the early intervention with GOS also facilitated the mRNA expression of Sodium glucose co-transporter 1(SGLT1) on d 8 and the m RNA expression of Glucose transporter type 2(GLUT2) on d 21(P 0.05).It was further determined that GOS up-regulated the m RNA expression of preproglucagon(GCG),insulin-like growth factor 1(IGF-1),insulin-like growth factor 1 receptor(IGF-1 R) and epidermal growth factor(EGF).GOS also up-regulated the protein expression of glucagon-like peptide-2(GLP-2) and EGF in the jejunum of the piglets.Furthermore,it was also found that GOS enhanced the protein expression of ZO-1 and occludin on d 8(P 0.05),as well as increased the mRNA expression of TGF-β and decrease the mRNA expression of IL-12(P 0.05).Conclusions: These results indicate that GOS have a positive effect on piglet growth performance in addition to decreasing the crypt depth and enhancing functional development in jejunum of suckling piglets.     

Dietary oregano aqueous extract improves growth performance and intestinal health of broilers through modulating gut microbial compositionsOA

Background Intestinal health plays a pivotal role in broiler chicken growth. Oregano aqueous extract(OAE) effectively exerts anti-inflammatory and antibacterial effects. However, the protective effects of OAE on intestinal health in broilers and the underlying mechanism remain unclear. This study aimed to investigate the potential effects of OAE on growth performance, the gut microbiota and intestinal health. A total of 840 1-d-old male and female broilers(Arbor Acres) were randomly allocated in...     

Mycotoxin binder improves growth rate in piglets associated with reduction of toll-like receptor-4 and increase of tight junction protein gene expression in gut mucosa

Background: Deoxynivalenol(DON) is a mycotoxin produced by Fusarium species in the field, commonly found in cereal grains, which negatively affects performances and health of animals. Mycotoxin binders are supposed to reduce the toxicity of mycotoxins.Method: The effect of a mycotoxin binder(containing acid-activated bentonite, clinoptilolite, yeast cell walls and organic acids) on growth performance and gut health was studied. Hundred and twenty weaning piglets were allocated to 4 treatments, with 5 pens of 6 piglets each, arranged in a 2 × 2 factorial design: control diet; control diet with 1 kg/t binder; control diet with DON; and control diet with DON and 1 kg/t binder. From d0–14,the diet of DON-challenged groups was artificially contaminated with a mixture of DON(2.6 mg/kg), 3-acetyldeoxynivalenol(0.1 mg/kg) and 15-acetyl-deoxynivalenol(0.3 mg/kg), after which the total contamination level was reduced to 1 mg/kg, until d37. On d14, one pig from each pen was euthanized and distal small intestinal mucosa samples were collected for the assessment of intestinal permeability, and gene expression of tight junction proteins, toll-like receptor 4, inflammatory cytokines and intestinal alkaline phosphatase.Results: After 37 d, there were no differences in growth performance between control and DON-challenged groups(P 0.05). Nevertheless, groups that received diets with binder had a significantly higher average daily gain(ADG) and average daily feed intake(ADFI) for the first 14 d as well as for the whole period, compared to groups without binder(P ≤ 0.05). Groups with binder in the diet also exhibited lower expression of toll-like receptor 4 in distal small intestinal mucosa at d14, compared to groups without binder(P ≤ 0.05). Interestingly, comparing the two DON treatments, piglets fed DON and binder had significantly higher ADFI and ADG compared to those with only DON for the first 14-d(P ≤ 0.05). Addition of binder to DON contaminated diets, also down-regulated the gene expression of toll-like receptor 4(P ≤ 0.05) and increased m RNA level zona occludens 1(P ≤ 0.10) as compared to DON.Conclusions: The present data provide evidence that the binder improves growth rate in piglets associated with reduction of toll-like receptor-4 and increase of tight junction protein gene expression. However, the current study does not allow to assess whether the effects of the binder are mediated by alterations in the toxicokinetics of the mycotoxin.     

Dietary bile acid supplementation in weaned piglets with intrauterine growth retardation improves colonic microbiota,metabolic activity,and epithelial function

Background Intrauterine growth retardation(IUGR) is one of the major constraints in animal production. Our previous study showed that piglets with IUGR are associated with abnormal bile acid(BA) metabolism. This study explored whether dietary BA supplementation could improve growth performance and colonic development, function, microbiota, and metabolites in the normal birth weight(NBW) and IUGR piglets. A total of 48 weaned piglets(24 IUGR and 24 NBW) were allocated to four groups(12 piglets pe...     

Changes in progenitors and differentiated epithelial cells of neonatal piglets

This study aimed to assess the changes of small intestinal morphology,progenitors,differentiated epithelial cells,and potential mechanisms in neonatal piglets.Hematoxylin and eosin staining of samples from 36 piglets suggested that dramatic changes were observed in the jejunum crypts depth and crypt fission index of neonatal piglets(P<0.001).The number of intestinal stem cells(ISC)tended to increase(P<0.10),and a decreased number of enteroendocrine cells appeared in the jejunal crypt on d 7(P<0.05).Furthermore,the mRNA expression of jejunal chromogranin A(ChgA)was down-regulated in d 7 piglets(P<0.05).There was an up-regulation of the adult ISC marker gene of SPARC related modular calcium binding 2(Smoc2),and Wnt/b-catenin target genes on d 7(P<0.05).These results were further verified in vitro enteroid culture experiments.A mass of hollow spheroids was cultured from the fetal intestine of 0-d-old piglets(P<0.001),whereas substantial organoids with budding and branching structures were cultured from the intestine of 7-d-old piglets(P<0.001).The difference was reflected by the organoid budding efficiency,crypt domains per organoid,and the surface area of the organoid.Furthermore,spheroids on d 0 had more Ki67-positive cells and enteroendocrine cells(P<0.05)and showed a decreasing trend in the ISC and goblet cells(P<0.10).Moreover,the mRNA expression of spheroids differed markedly from that of organoids,with low expression of intestinal differentiation gene(Lysozyme;P<0.05),epithelial-specific markers(Villin,E-cadherin;P<0.05),and adult ISC markers(leucine-rich repeat-containing G protein-coupled receptor 5[Lgr5],Smoc2;P<0.001),and upregulation of fetal marker(connexin 43[Cnx43];P<0.05).The mRNA expression of relevant genes was up-regulated,and involved in Wnt/b-catenin,epidermal growth factor(EGF),Notch,and bone morphogenetic protein(BMP)signaling on d 7 organoids(P<0.05).Spheroids displayed low differentiated phenotype and high proliferation,while organoids exhibited strong differentiation potential.These results indicated that the conversion from the fetal progenitors(spheroids)to adult ISC(normal organoids)might largely be responsible for the fast development of intestinal epithelial cells in neonatal piglets.     

Dietary supplementation with branched-chain amino acids enhances milk production by lactating sows and the growth of suckling pigletsOA

Background: Under current dietary regimens, milk production by lactating sows is insufficient to sustain the maximal growth of their piglets. As precursors of glutamate and glutamine as well as substrates and activators of protein synthesis, branched-chain amino acids(BCAAs) have great potential for enhancing milk production by sows.Methods: Thirty multiparous sows were assigned randomly into one of three groups: control(a corn-and soybean meal-based diet), the basal diet + 1.535% BCAAs; and the...     

The prolonged effect of glucagon-like peptide 2 pretreatment on growth performance and intestinal development of weaned piglets

Background: Glucagon-like peptide 2(GLP-2) is a potent epithelium-specific intestinal growth factor. The aim of this study was to demonstrate the prolonged effect of GLP-2 on the growth performance of weaned piglets. Forty piglets weaned at the age of 28 d with an average BW of 6.8 ± 0.4 kg were assigned to four treatments:(i) nonchallenged control;(ii) LPS-challenged control;(iii) LPS + low GLP-2; and(iv) LPS + high GLP-2. Piglets in groups(i),(ii), and(iv) were s.c. injected with PBS supplemented with human [Gly2]GLP-21-34 at doses of 0, 2 and 10 nmol/kg BW per day for seven consecutive days. BW, gain:feed ratio(G:F), and plasma GLP-2 levels were determined on d 0,7, and 14 after weaning. Piglets were challenged with i.p. administration of Escherichia coli lipopolysaccharide(LPS)at a dose of 100 μg/kg on d 14 to induce intestinal damage. Twenty-four hours later, intestinal tract samples were collected to assess intestinal morphology and quantify enzyme activity.Results: Plasma GLP-2 levels decreased after weaning, but in the high GLP-2 group, plasma GLP-2 was maintained on d 7 and even increased to a level higher than the preweaning level on d 14(P 0.05). High GLP-2 treatment significantly increased the duodenal, jejunal and ileal weight, as well as the gross weight of the small intestine(SI),and the SI weight index(P 0.05). LPS caused villous atrophy and disrupted intestinal morphology in the duodenum, jejunum and ileum. GLP-2 also significantly increased the villus height and the villus height/crypt depth ratio(VCR) of the duodenum, jejunum, and ileum(P 0.05). Histological examination revealed that in GLP-2-treated groups, the integrity of the villus was maintained, and the villus was protected against LPS-induced damage. GLP-2 significantly increased the activity of alkaline phosphatase(AKP), γ-glutamyltranspeptidase(γ-GT), and pancreatic lipase in the duodenum and jejunum(P 0.05). GLP-2 treatment also significantly increased the average daily gain(ADG) and G:F of piglets at 0 to 7, 7 to 14, as well as 0 to14 d(P 0.05), resulting in a significant increase of final BW in high GLP-2 pigs(P = 0.016).Conclusions: Exogenous GLP-2 improved the growth of weaned piglets and protected them against LPS-induced intestinal damage. These effects may be due to the ability of GLP-2 to promote the secretion of endogenous GLP-2 to stimulate the small intestinal development.