Supplemental Clostridium butyricum modulates lipid metabolism by reshaping the gut microbiota composition and bile acid profile in IUGR suckling piglets

Background Intrauterine growth restriction(IUGR)can cause lipid disorders in infants and have long-term adverse effects on their growth and development.Clostridium butyricum(C.butyricum),a kind of emerging probiotics,has been reported to effectively attenuate lipid metabolism dysfunctions.Therefore,the objective of this study was to investigate the effects of C.butyricum supplementation on hepatic lipid disorders in IUGR suckling piglets.Methods Sixteen IUGR and eight normal birth weight(NBW)neonatal male piglets were used in this study.From d 3to d 24,in addition to drinking milk,the eight NBW piglets(NBW-CON group,n=8)and eight IUGR piglets(IUGR-CON group,n=8)were given 10 mL sterile saline once a day,while the remaining IUGR piglets(IUGR-CB group,n=8)were orally administered C.butyricum at a dose of 2×108colony-forming units(CFU)/kg body weight(suspended in 10 mL sterile saline)at the same frequency.Results The IUGR-CON piglets exhibited restricted growth,impaired hepatic morphology,disordered lipid metabolism,increased abundance of opportunistic pathogens and altered ileum and liver bile acid(BA)profiles.However,C.butyricum supplementation reshaped the gut microbiota of the IUGR-CB piglets,characterized by a decreased abundance of opportunistic pathogens in the ileum,including Streptococcus and Enterococcus.The decrease in these bile salt hydrolase(BSH)-producing microbes increased the content of conjugated BAs,which could be transported to the liver and function as signaling molecules to activate liver X receptorα(LXRα)and farnesoid X receptor(FXR).This activation effectively accelerated the synthesis and oxidation of fatty acids and down-regulated the total cholesterol level by decreasing the synthesis and promoting the efflux of cholesterol.As a result,the growth performance and morphological structure of the liver improved in the IUGR piglets.Conclusion These results indicate that C.butyricum supplementation in IUGR suckling piglets could decrease the abundance of BSH-producing microbes(Streptococcus and Enterococcus).This decrease altered the ileum and liver BA profiles and consequently activated the expression of hepatic LXRαand FXR.The activation of these two signaling molecules could effectively normalize the lipid metabolism and improve the growth performance of IUGR suckling piglets.

Pterostilbene attenuates intrauterine growth retardation-induced colon inflamm tion in piglets by modulating endoplasmic reticulum stress and autophagy

Background:Endoplasmic reticulum(ER)stress and autophagy are implicated in the pathophysiology of intestinal inflammation;however,their roles in intrauterine growth retardation(IUGR)-induced colon inflammation are unclear.This study explored the protective effects of natural stilbene pterostilbene on colon inflammation using the IUGR piglets and the tumor necrosis factor alpha(TNF-α)-treated human colonic epithelial cells(Caco-2)by targeting ER stress and autophagy.Results:Both the IUGR colon and the TNF-α-treated Caco-2 cells exhibited inflammatory responses,ER stress,and impaired autophagic flux(P<0.05).The ER stress inducer tunicamycin and the autophagy inhibitor 3-methyladenine further augmented inflammatory responses and apoptosis in the TNF-α-treated Caco-2 cells(P<0.05).Conversely,pterostilbene inhibited ER stress and restored autophagic flux in the IUGR colon and the TNF-α-treated cells(P<0.05).Pterostilbene also prevented the release of inflammatory cytokines and nuclear translocation of nuclear factor kappa B p65,reduced intestinal permeability and cell apoptosis,and facilitated the expression of intestinal tight junction proteins in the IUGR colon and the TNF-α-treated cells(P<0.05).Importantly,treatment with tunicamycin or autophagosome-lysosome binding inhibitor chloroquine blocked the positive effects of pterostilbene on inflammatory response,cell apoptosis,and intestinal barrier function in the TNF-α-exposed Caco-2 cells(P<0.05).Conclusion:Pterostilbene mitigates ER stress and promotes autophagic flux,thereby improving colon inflammation and barrier dysfunction in the IUGR piglets and the TNF-α-treated Caco-2 cells.

Comparison of the protective effects of resveratrol and pterostilbene against intestinal damage and redox imbalance in weanling piglets

Background: Evidence indicates that early weaning predisposes piglets to intestinal oxidative stress and increases the risk of intestinal dysfunction;however, there are minimal satisfactory treatment strategies for these conditions.This study investigated the potential of resveratrol and its analog, pterostilbene, as antioxidant protectants for regulating intestinal morphology, barrier function, and redox status among weanling piglets.Methods: A total of 144 piglets were selected at 21 days of age and randomly allocated into one of four treatment groups, each of which included six replicates. Piglets in a sow-reared control group were suckling normally between ages 21 and 28 days, while those in weaned groups were fed a basal diet, supplemented with either 300 mg/kg of resveratrol or with 300 mg/kg of pterostilbene. Parameters associated with intestinal injury and redox status were analyzed at the end of the feeding trial.Results: Early weaning disrupted the intestinal function of young piglets, with evidence of increased diamine oxidase activity and D-lactate content in the plasma, shorter villi, an imbalance between cell proliferation and apoptosis, an impaired antioxidant defense system, and severe oxidative damage in the jejunum relative to suckling piglets. Feeding piglets with a resveratrol-supplemented diet partially increased villus height(P = 0.056) and tended to diminish apoptotic cell numbers(P = 0.084) in the jejunum compared with those fed a basal diet. Similarly, these beneficial effects were observed in the pterostilbene-fed piglets. Pterostilbene improved the feed efficiency of weanling piglets between the ages of 21 and 28 days;it also resulted in diminished plasma diamine oxidase activity and D-lactate content relative to untreated weaned piglets(P < 0.05). Notably, pterostilbene restored jejunal antioxidant capacity, an effect that was nearly absent in the resveratrol-fed piglets. Pterostilbene reduced the malondialdehyde and 8-hydroxy-2′-deoxyguanosine contents of jejunal mucosa possibly through its regulatory role in facilitating the nuclear translocation of nuclear factor erythroid-2-related factor 2 and the expression levels of NAD(P)H quinone dehydrogenase 1 and superoxide dismutase 2(P < 0.05).Conclusions: The results indicate that pterostilbene may be more effective than its parent compound in alleviating early weaning-induced intestinal damage and redox imbalance among young piglets.

Resveratrol and its derivative pterostilbene ameliorate intestine injury in intrauterine growth-retarded weanling piglets by modulating redox status and gut microbiota

Background:Intestinal disorder is an important factor contributing to growth lag and high rates of morbidity and mortality of piglets with intrauterine growth retardation(IUGR).Resveratrol(RSV)and its derivative pterostilbene(PT)are natural stilbenes possessing various bioactivities,such as antioxidative and anti-inflammatory effects.This study compared the protective potential of RSV and PT on the intestinal redox status and gut microbiota in weanling piglets with IUGR.Methods:Eighteen male piglets of normal body weight(NBW)and 54 same-sex IUGR piglets were chosen according to their birth and weaning weights.The NBW piglets accepted a basal diet,while the IUGR piglets were allotted to one of three groups according to their body weight at weaning and received a basal diet,an RSV-supplemented diet(300 mg/kg),or a PT-supplemented diet(300 mg/kg),respectively.Results:Compared with IUGR piglets,both RSV and PT improved the IUGR-associated decrease in jejunal villus height and increases in plasma diamine oxidase activity and D-lactate level and jejunal apoptosis of piglets(P<0.05).Administering RSV and PT also enhanced jejunal superoxide dismutase activity and the mRNA and protein expression of superoxide dismutase 2 of IUGR piglets by promoting nuclear factor erythroid 2-related factor 2(Nrf2)nuclear translocation(P<0.05).Comparatively,PT was more effective than RSV in elevating the villus height/crypt depth ratio and occludin mRNA and protein levels in the jejunum of IUGR piglets(P<0.05).PT was also superior to RSV in increasing Nrf2 nuclear translocation and inhibiting malondialdehyde accumulation in the jejunum of IUGR piglets(P<0.05).Additionally,RSV modulated the composition of cecal microbiota of IUGR piglets,as evidenced by increasing the prevalence of the phylum Bacteroidetes and the genera Prevotella,Faecalibacterium,and Parabacteroides and inhibiting the growth of the phylum Proteobacteria and its genera Escherichia and Actinobacillus(P<0.05).Moreover,RSV significantly increased the butyrate concentration in the cecum of IUGR piglets(P<0.05).Conclusion:PT is more potent than RSV to prevent intestinal oxidative stress,while RSV has a stronger capacity to regulate gut microbiota compared to PT.