Protective effect of Broussonetia papyrifera leaf polysaccharides on intestinal integrity in a rat model of diet-induced oxidative stress.

This study aimed to investigate the effect of Broussonetia papyrifera polysaccharides (BPP) on the jejunal intestinal integrity of rats ingesting oxidized fish oil (OFO) induced oxidative stress. Polysaccharides (Mw 16,956 Da) containing carboxyl groups were extracted from Broussonetia papyrifera leaves. In vitro antioxidant assays showed that this polysaccharide possessed antioxidant capabilities. Thirty-two male weaned rats were allocated into two groups orally infused BPP solution and PBS for 26 days, respectively. From day 9 to day 26, half of the rats in each group were fed food containing OFO, where the lipid peroxidation can induce intestinal oxidative stress. OFO administration resulted in diarrhea, decreased growth performance (p < 0.01), impaired jejunal morphology (p < 0.05) and antioxidant capacity (p < 0.01), increased the levels of ROS and its related products, IL-1ß and IL-17 (p < 0.01) of jejunum, as well as down-regulated Bcl-2/Bax (p < 0.01) and Nrf2 signaling (p < 0.01) of jejunum in rats. BPP gavage effectively alleviated the negative effects of OFO on growth performance, morphology, enterocyte apoptosis, antioxidant capacity and inflammation of jejunum (p < 0.05) in rats. In the oxidative stress model cell assay, the use of receptor inhibitors inhibited the enhancement of antioxidant capacity by BPP. These results suggested that BPP protected intestinal morphology, thus improving growth performance and reducing diarrhea in rats ingesting OFO. This protective effect may be attributed to scavenging free radicals and activating the Nrf2 pathway, which enhances antioxidant capacity, consequently reducing inflammation and mitigating intestinal cell death.

Leucine alleviates cytokine storm syndrome by regulating macrophage polarization via the mTORC1/LXRα signaling pathway.

Cytokine storms are associated with severe pathological damage and death in some diseases. Excessive activation of M1 macrophages and the subsequent secretion of pro-inflammatory cytokines are a major cause of cytokine storms. Therefore, promoting the polarization of M2 macrophages to restore immune balance is a promising therapeutic strategy for treating cytokine storm syndrome (CSS). This study was aimed at investigating the potential protective effects of leucine on lipopolysaccharide (LPS)-induced CSS in mice and exploring the underlying mechanisms. CSS was induced by LPS administration in mice, which were concurrently administered leucine orally. In vitro, bone marrow derived macrophages (BMDMs) were polarized to M1 and M2 phenotypes with LPS and interleukin-4 (IL-4), respectively, and treated with leucine. Leucine decreased mortality in mice treated with lethal doses of LPS. Specifically, leucine decreased M1 polarization and promoted M2 polarization, thus diminishing pro-inflammatory cytokine levels and ameliorating CSS in mice. Further studies revealed that leucine-induced macrophage polarization through the mechanistic target of rapamycin complex 1 (mTORC1)/liver X receptor α (LXRα) pathway, which synergistically enhanced the expression of the IL-4-induced M2 marker Arg1 and subsequent M2 polarization. In summary, this study revealed that leucine ameliorates CSS in LPS mice by promoting M2 polarization through the mTORC1/LXRα/Arg1 signaling pathway. Our findings indicate that a fundamental link between metabolism and immunity contributes to the resolution of inflammation and the repair of damaged tissues.

All-trans retinoic acid alleviates transmissible gastroenteritis virus-induced intestinal inflammation and barrier dysfunction in weaned piglets.

BACKGROUND: Transmissible gastroenteritis virus (TGEV) is one of the main pathogens causing severe diarrhea of piglets. The pathogenesis of TGEV is closely related to intestinal inflammation. All-trans retinoic acid (ATRA) is the main active metabolite of vitamin A, which has immunomodulatory and anti-inflammatory properties. However, it is unclear whether ATRA can alleviate TGEV-induced intestinal inflammation and barrier dysfunction in piglets. This study aimed to investigate the effects of ATRA on growth performance, diarrhea, intestinal inflammation and intestinal barrier integrity of TGEV-challenged piglets. METHODS: In a 19-d study, 32 weaned piglets were randomly divided into 4 treatments: Control group (basal diet), TGEV group (basal diet + TGEV challenge), TGEV + ATRA5 group (basal diet + 5 mg/d ATRA + TGEV challenge) and TGEV + ATRA15 group (basal diet + 15 mg/d ATRA + TGEV challenge). On d 14, piglets were orally administered TGEV or the sterile medium. RESULTS: Feeding piglets with 5 and 15 mg/d ATRA alleviated the growth inhibition and diarrhea induced by TGEV (P < 0.05). Feeding piglets with 5 and 15 mg/d ATRA also inhibited the increase of serum diamine oxidase (DAO) activity and the decrease of occludin and claudin-1 protein levels in jejunal mucosa induced by TGEV, and maintained intestinal barrier integrity (P < 0.05). Meanwhile, 5 mg/d ATRA feeding increased the sucrase activity and the expressions of nutrient transporter related genes (GLUT2 and SLC7A1) in jejunal mucosa of TGEV-challenged piglets (P < 0.05). Furthermore, 5 mg/d ATRA feeding attenuated TGEV-induced intestinal inflammatory response by inhibiting the release of interleukin (IL)-1ß, IL-8 and tumor necrosis factor-α (TNF-α), and promoting the secretion of IL-10 and secretory immunoglobulin A (sIgA) (P < 0.05). Feeding 5 mg/d ATRA also down-regulated the expressions of Toll-like receptors and RIG-I like receptors signaling pathway related genes (TLR3, TLR4, RIG-I, MyD88, TRIF and MAVS) and the phosphorylation level of nuclear factor-κB-p65 (NF-κB p65), and up-regulated the inhibitor kappa B alpha (IκBα) protein level in jejunal mucosa of TGEV-challenged piglets (P < 0.05). CONCLUSIONS: ATRA alleviated TGEV-induced intestinal barrier damage by inhibiting inflammatory response, thus improving the growth performance and inhibiting diarrhea of piglets. The mechanism was associated with the inhibition of NF-κB signaling pathway mediated by TLR3, TLR4 and RIG-I.

Purine Metabolism and Hexosamine Biosynthetic Pathway Abnormalities in Diarrheal Weaned Piglets Identified Using Metabolomics.

Post-weaning diarrhea significantly contributes to the high mortality in pig production, but the metabolic changes in weaned piglets with diarrhea remain unclear. This study aimed to identify the differential metabolites in the urine of diarrheal weaned piglets and those of healthy weaned piglets to reveal the metabolic changes associated with diarrhea in weaned piglets. Nine 25-day-old piglets with diarrhea scores above 16 and an average body weight of 5.41 ± 0.18 kg were selected for the diarrhea group. Corresponding to the body weight and sex of the diarrhea group, nine 25-month-old healthy piglets with similar sex and body weights of 5.49 ± 0.21 kg were selected as the control group. Results showed that the serum C-reactive protein and cortisol of piglets in the diarrhea group were higher than those in the control group (p < 0.05). The mRNA expression of TNF-α, IFN-γ in the jejunum and colon, and IL-1ß in the jejunum were increased in diarrhea piglets (p < 0.05), accompanied by a reduction in the mRNA expression of ZO-1, ZO-2, and CLDN1 in the jejunum and colon (p < 0.05); mRNA expression of OCLN in the colon also occurred (p < 0.05). Metabolomic analysis of urine revealed increased levels of inosine, hypoxanthine, guanosine, deoxyinosin, glucosamine, glucosamine-1-p, N-Acetylmannosamine, chitobiose, and uric acid, identified as differential metabolites in diarrhea piglets compared to the controls. In summary, elevated weaning stress and inflammatory disease were associated with the abnormalities of purine metabolism and the hexosamine biosynthetic pathway of weaned piglets. This study additionally indicated the presence of energy metabolism-related diseases in diarrheal weaned piglets.

Retinoic acid alleviates rotavirus-induced intestinal damage by regulating redox homeostasis and autophagic flux in piglets.

Rotaviruses (RV) are a major cause of severe gastroenteritis, particularly in neonatal piglets. Despite the availability of effective vaccines, the development of antiviral therapies for RV remains an ongoing challenge. Retinoic acid (RA), a metabolite of vitamin A, has been shown to have anti-oxidative and antiviral properties. However, the mechanism by which RA exerts its intestinal-protective and antiviral effects on RV infection is not fully understood. The study investigates the effects of RA supplementation in Duroc × Landrace × Yorkshire (DLY) piglets challenged with RV. Thirty-six DLY piglets were assigned into six treatments, including a control group, RA treatment group with two concentration gradients (5 and 15 mg/d), RV treatment group, and RV treatment group with the addition of different concentration gradients of RA (5 and 15 mg/d). Our study revealed that RV infection led to extensive intestinal architecture damage, which was mitigated by RA treatment at lower concentrations by increasing the villus height and villus height/crypt depth ratio (P < 0.05), enhancing intestinal stem cell signaling and promoting intestinal barrier functions. In addition, 15 mg/d RA supplementation significantly increased NRF2 and HO-1 protein expression (P < 0.05) and GSH content (P < 0.05), indicating that RA supplementation can enhance anti-oxidative signaling and redox homeostasis after RV challenge. Additionally, the research demonstrated that RA exerts a dual impact on the regulation of autophagy, both stimulating the initiation of autophagy and hindering the flow of autophagic flux. Through the modulation of autophagic flux, RA influence the progression of RV infection. These findings provide new insights into the regulation of redox hemostasis and autophagy by RA and its potential therapeutic application in RV infection.

Yucca schidigera purpurea-sourced arabinogalactan polysaccharides augments antioxidant capacity facilitating intestinal antioxidant functions.

This study isolated and purified a novel homogeneous arabinogalactan polysaccharide from Yucca schidigera extract (YSE), unveiled its unique structure and explored its antioxidant function. Firstly, the antioxidant potential of YSE was demonstrated in piglet trials. A homogeneous polysaccharide with a molecular weight of 24.2 kDa, designated as Yucca schidigera polysaccharide B (YPB), was isolated and purified from YSE. The monosaccharide composition of YPB was Rha, Araf, Galp, and Glcp, whose molar percentages were 2.8 %, 11.6 %, 45.5 %, and 40.0 %, respectively. Methylation analysis combined with 1D and 2D nuclear magnetic resonance showed that YPB was a complex polysaccharide with a main glycosidic linkage pattern of →2)-α-ʟ-Rha-(1 â†’ 3)-ß-ᴅ-Galp-(1→3)-ß-ᴅ-Galp-(1 â†’ 3)-ß-ᴅ-Galp-(1 â†’ 3)-ß-ᴅ-Glcp-(1→, and branched Araf and Galp fragments were connected with the main chain through →3,6)-ß-ᴅ-Galp-(1→, →3,4)-ß-ᴅ-Glcp-(1→, and →2,4)-α-ʟ-Rha-(1→ linkages. Following the in vitro biochemical assays of bioactive components, YPB should be the contributor to the antioxidant activity in YSE. Based on the establishment of oxidative stress model, YPB exhibited strong antioxidant capacity and activated NRF2 pathway, and then provided protection against the damage induced oxidative stress in IPEC-J2 cells and rats. Further analysis with inhibitors found that this antioxidant effect was attributed to its interaction with epidermal growth factor receptor and mannose receptor, and stimulating PI3K/AKT pathway.

Corrigendum: Combined effects of host genetics and diet on porcine intestinal fungi and their pathogenic genes.

[This corrects the article DOI: 10.3389/fmicb.2023.1192288.].

Genetic- and Fiber-Diet-Mediated Changes in Antibiotic Resistance Genes in Pig Colon Contents and Feces and Their Driving Factors.

Comprehensive studies on the effects of genetics and fiber diets on antibiotic resistance genes (ARGs) remain scarce. In this study, we analyzed the profiles of ARGs in colonic contents and fecal samples of Taoyuan, Duroc, and Xiangcun pigs (n = 10) fed at different fiber levels. Through macrogenomic analysis, we identified a total of 850 unique types of ARGs and classified them into 111 drug resistance classes. The abundance of partially drug-resistant ARGs was higher in the colonic contents of local pig breeds under a large-scale farming model. ARGs were found to be widely distributed among a variety of bacteria, predominantly in the phyla Firmicutes, Proteobacteria, and Bacteroidetes. Fiber diets reduce the abundance of ARGs in colonic contents and feces, and mobile genetic elements (MGEs) and short-chain fatty acids (SCFAs) are important drivers in mediating the effect of fiber diets on the abundance of ARGs. In vitro fermentation experiments confirmed that butyric acid significantly reduced the abundance of ARGs. In summary, the results of this study enhanced our understanding of the distribution and composition of ARGs in the colon of different breeds of pigs and revealed that a fiber diet can reduce ARGs in feces through its Butyric acid, providing reference data for environmental safety.

Effect of Different Dietary Lipid Sources on Growth Performance, Nutrient Digestibility, and Intestinal Health in Weaned Pigs.

To investigate the effects of lipid sources on growth performance and intestinal health, 72 weaned pigs were randomly allocated to three treatments. Pigs were fed with a corn-soybean meal diet containing 2% soybean oil (SO), or fish-palm-rice oil mixture (FPRO), or coconut-palm-rice oil mixture (CPRO). The trial lasted for 28 days; blood and intestinal tissue samples were collected. The results showed that the crude fat digestibility of the FPRO group was higher than that of the SO and CPRO groups (p < 0.05). The FPRO group also had higher digestibility of dry matter, ash, and gross energy than the SO group (p < 0.05); compared to the SO group, the serum interlukin-6 (IL-6) concentration was decreased. Interestingly, the FPRO and CPRO groups had higher villus height than the SO group in the jejunum and ileum, respectively (p < 0.05). Moreover, the FPRO group had higher Lactobacillus abundance than the SO group in the colon and cecum (p < 0.05). Importantly, the expression levels of tight junction protein ZO-1, Claudin-1, and Occludin in the duodenal and ileal mucosa were higher in the FPRO group than in the SO and CPRO groups (p < 0.05). The expression levels of nutrient transporters such as the CAT-1, PepT1, FATP1, and SGLT1 were higher in the FPRO group than in the SO group (p < 0.05). The improved digestibility and intestinal epithelium functions, as well as the reduced inflammatory cytokines, in the FPRO and CPRO group suggest that a mixed lipid source such as the FPRO deserves further attention.

Combined effects of host genetics and diet on porcine intestinal fungi and their pathogenic genes.

As research on gut microbes progresses, it becomes increasingly clear that a small family of microbiota--fungi, plays a crucial role in animal health. However, little is known about the fungal composition in the pig intestine, especially after a dietary fiber diet and hybrid genetics, and the changes in host pathogenicity-associated genes they carry. The purpose of this study is to investigate the effects of diet and genetics on the diversity and structure of porcine intestinal fungi and to describe, for the first time, the host pathogenicity-related genes carried by porcine intestinal fungi. Samples of colonic contents were collected for metagenomic analysis using a 3 × 2 parsing design, where three pig breeds (Taoyuan, Duroc, and crossbred Xiangcun) were fed high or low fiber diets (n = 10). In all samples, we identified a total of 281 identifiable fungal genera, with Ascomycota and Microsporidia being the most abundant fungi. Compared to Duroc pigs, Taoyuan and Xiangcun pigs had higher fungal richness. Interestingly, the fiber diet significantly reduced the abundance of the pathogenic fungus Mucor and significantly increased the abundance of the fiber digestion-associated fungus Neocallimastix. Pathogenic fungi exert their pathogenicity through the genes they carry that are associated with host pathogenicity. Therefore, we obtained 839 pathogenicity genes carried by the spectrum of fungi in the pig intestine by comparing the PHI-base database. Our results showed that fungi in the colon of Taoyuan pigs carried the highest abundance of different classes of host pathogenicity-related genes, and the lowest in Duroc pigs. Specifically, Taoyuan pigs carried high abundance of animal pathogenicity-related genes (CaTUP1, CPAR2_106400, CaCDC35, Tfp1, CaMNT2), and CaTUP1 was the key gene for Candida pathogenicity. The intestinal fungal composition of crossbred Xiangcun pigs and the abundance of host pathogenicity-associated genes they carried exhibited a mixture of characteristics of Taoyuan and Duroc pigs. In conclusion, our results provide the first comprehensive report on the effects of dietary fiber and genetics on the composition of intestinal fungi and the host-associated pathogenicity genes they carry in pigs. These findings provide a reference for subsequent pig breeding and development of anti-pathogenic fungal drugs.

Iron overload induces colitis by modulating ferroptosis and interfering gut microbiota in mice.

BACKGROUND: Iron plays a pivotal role in various physiological processes, including intestinal inflammation, ferroptosis, and the modulation of the gut microbiome. However, the way these factors interact with each other is unclear. METHODS: Mice models were fed with low, normal and high iron diets to assess their impacts on colitis, ferroptosis and gut microbiota. Untargeted fecal metabolomics analysis, 16S rRNA sequencing, histopathology analysis, real-time quantitative PCR and western blot were performed to analyze the differences in the intestinal inflammatory response and understanding its regulatory mechanisms between low, normal and high iron groups. RESULTS: The iron overload changed the serum iron, colon iron and fecal iron. In addition, the iron overload induced the colitis, induced the ferroptosis and altered the microbiome composition in the fecal of mice. By using untargeted fecal metabolomics analysis to screen of metabolites in the fecal, we found that different metabolomics profiles in the fecal samples between iron deficiency, normal iron and iron overload groups. The correlation analysis showed that both of iron deficiency and overload were closely related to Dubosiella. The relationship between microbial communities (e.g., Akkermansia, Alistipes, and Dubosiella) and colitis-related parameters was highly significant. Additionally, Alistipes and Bacteroides microbial communities displayed a close association with ferroptosis-related parameters. Iron overload reduced the concentration of metabolites, which exert the anti-inflammatory effects (e.g., (+)-.alpha.-tocopherol) in mice. The nucleotide metabolism, enzyme metabolism and metabolic diseases were decreased and the lipid metabolism was increased in iron deficiency and iron overload groups compared with normal iron group. CONCLUSION: Iron overload exacerbated colitis in mice by modulating ferroptosis and perturbing the gut microbiota. Iron overload-induced ferroptosis was associated with NRF2/GPX-4 signaling pathway. Specific microbial taxa and their associated metabolites were closely intertwined with both colitis and ferroptosis markers.

Effects of different starch structures on energy metabolism in pigs.

BACKGROUND: Starch is a major component of carbohydrates and a major energy source for monogastric animals. Starch is composed of amylose and amylopectin and has different physiological functions due to its different structure. It has been shown that the energy supply efficiency of amylose is lower than that of amylopectin. However, there are few studies on the effect of starch structure on the available energy of pigs. The purpose of this study was to measure the effect of different structures of starch in the diet on the net energy (NE) of pigs using a comparative slaughter method and to establish a prediction equation to estimate the NE of starch with different structures. Fifty-six barrows (initial BW 10.18 ± 0.11 kg) were used, and they were housed and fed individually. Pigs were divided into 7 treatments, with 8 replicates for each treatment and 1 pig for each replicate. One of the treatments was randomly selected as the initial slaughter group (ISG). Pigs in the remaining treatments were assigned to 6 diets, fed with basic diet and semi-pure diets with amylose/amylopectin ratio (AR) of 3.09, 1.47, 0.25, 0.15 and 0.12, respectively. The experiment lasted for 28 d. RESULTS: Results showed that compared with the high amylose (AM) groups (AR 3.09 and 1.47), the high amylopectin (AP) group (AR 0.15) significantly increased the final BW, average daily weight gain and average daily feed intake of pigs (P < 0.05), but the F:G of the AM group was lower (P < 0.01). In addition, AR 0.15 and 0.12 groups have higher (P < 0.01) nutrient digestibility of dry matter, crude protein, gross energy and crude ash. Meanwhile, compared with other groups, AR 0.15 group has a higher (P < 0.05) NE intake and energy retention (RE). The regressive equation for predicting with starch structures was established as RE = 1,235.243 - 48.298AM/AP (R2 = 0.657, P = 0.05). CONCLUSIONS: In conclusion, NE intake and RE of pigs augmented with the increase of dietary amylopectin content, indicating that diets high in amylopectin were more conducive to promoting the growth of pigs in the late conservation period.

Effect of small peptide chelated iron on growth performance, immunity and intestinal health in weaned pigs.

BACKGROUND: Small peptide chelated iron (SPCI), a novel iron supplementation in pig diets, owns growth-enhancing characteristics. Although a number of researches have been performed, there is no clear-cut evidence to show the exact relationship between the dose and effects of small peptide chelated minerals. Therefore, we investigated the effect of dietary supplementation of SPCI at different doses in the growth performance, immunity, and intestinal health in weaned pigs. METHODS: Thirty weaned pigs were randomly assigned into five groups and feed with basal diet or the basal diet containing 50, 75, 100, or 125 mg/kg Fe as SPCI diets. The experiment lasted for 21 d and on day 22, blood samples were collected 1 h later. The tissue and intestinal mucosa samples were collected following. RESULTS: Our results showed that the feed to gain ratio (F:G) decreased with different levels of SPCI addition (P < 0.05). The average daily gain (ADG) (P < 0.05) and digestibility of crude protein (P < 0.01) decreased with 125 mg/kg SPCI addition. With dietary different levels of SPCI addition, the serum concentrations of ferritin (quadratic, P < 0.001), transferrin (quadratic, P < 0.001), iron content in liver (quadratic, P < 0.05), gallbladder (quadratic, P < 0.01) and fecal (quadratic, P < 0.01) increased quadraticly. While the iron content in tibia (P < 0.01) increased by 100 mg/kg SPCI supplementation. Dietary 75 mg/kg SPCI addition increased the serum insulin-like growth factor I (IGF-I) (P < 0.01) and SPCI (75 ~ 100 mg/kg) addition also increased the serum content of IgA (P < 0.01). The serum concentrations of IgG (quadratic, P < 0.05) and IgM (quadratic, P < 0.01) increased quadraticly by different levels of SPCI supplementation. Moreover, different levels of SPCI supplementation decreased the serum concentration of D-lactic acid (P < 0.01). The serum glutathione peroxidase (GSH-Px) (P < 0.01) elevated but the malondialdehyde (MDA) (P < 0.05) decreased by 100 mg/kg SPCI addition. Interestingly, SPCI supplementation at 75 ~ 100 mg/kg improved the intestinal morphology and barrier function, as suggested by enhanced villus height (P < 0.01) and villus height/crypt depth (V/C) (P < 0.01) in duodenum, as well as jejunum epithelium tight-junction protein ZO-1 (P < 0.01). Moreover, SPCI supplementation at 75 ~ 100 mg/kg increased the activity of duodenal lactase (P < 0.01), jejunal sucrase (P < 0.01) and ileal maltase (P < 0.01). Importantly, the expression levels of divalent metal transporter-1(DMT1) decreased with different levels of SPCI addition (P < 0.01). In addition, dietary SPCI supplementation at 75 mg/kg elevated the expression levels of critical functional genes such as peptide transporter-1(PePT1) (P = 0.06) and zinc transporter 1 (ZnT1) (P < 0.01) in ileum. The expression levels of sodium/glucose co-transporter-1 (SGLT1) in ileum (quadratic, P < 0.05) increased quadraticly by different levels of SPCI addition and amino acid transporter-1 (CAT1) in jejunum(P < 0.05) also increased by 100 mg/kg SPCI addition. CONCLUSIONS: Dietary SPCI supplementation at 75 ~ 100 mg/kg improved growth performance by elevated immunity and intestinal health.

Effect of 3-caffeoylquinic acid on growth performance, nutrient digestibility, and intestinal functions in weaned pigs.

Phenolic acid like with the 3-caffeoylquini acid (3-CQA) is formed by caffeic acid and qunic acid. This study was conducted to explore the effect of 3-CQA on growth performance and intestinal functions in weaned pigs. A total of 180 weaned pigs were randomly allocated into five treatments with 6 replicate pens per treatment (6 pigs per pen). Pigs in the control group (CON) were fed with basal diet (BD), and the others in the experimental groups were fed with BD and supplemented with 12.5, 25, 50, and 100 mg/kg 3-CQA. On day 43, the blood sample-collected pigs in the CON and optimal-dose group (only based on growth performance) were picked, and housed in metabolism cages (a total of 12 pigs, N = 6). 3-CQA increased the feed efficiency from days 21 to 42 of the trial and throughout the trial (P < 0.05). 3-CQA increased the serum concentrations of total protein, albumin, and total cholesterol (P < 0.05). Moreover, 3-CQA supplementation at 25 mg/kg increased the apparent digestibility of DM, energy, and ash (P < 0.05). Interestingly, 3-CQA decreased the crypt depth but increased the ratio of villus height to crypt depth in the jejunum and ileum (P < 0.05). Moreover, 3-CQA also increased the activities of sucrase, lactase, and catalase in the jejunal mucosa, and increased the activities of alkaline phosphatase and superoxide dismutase in the ileal mucosa (P < 0.05). 3-CQA also increased the abundance of secretory immunoglobulin A in the ileal mucosa (P < 0.05). Importantly, 3-CQA not only elevated the expression levels of critical functional genes such as the zonula occludens-1 , occludin, solute carrier family 7 , and nuclear factor erythroid 2-related factor 2 (Nrf2) in the duodenum but also elevated the expression levels of divalent metal transporter-1 and Nrf2 in the jejunum (P < 0.05). These results suggested a positive effect of 3-CQA supplementation on the growth and intestinal functions of weaned pigs. The mechanisms of action may be associated with elevated anti-oxidant capacity and improved intestinal barrier functions.

In last decades, swine producers used antibiotics as growth promoter added into diet. However, the pharmaceutical use of antibiotics is prohibited by the legislation of several countries due to potential health and environmental concerns. Therefore, the development of substitutes for traditionally used antibiotics has attracted considerable research interest worldwide. Natural phnolic acid like with the 3-CQA is an important component of biologically active phenols isolated from various natural plants. This study was carried out to evaluate the effect of 3-CQA on growth performance, nutrient digestibility, and intestinal functions in pigs. Results indicated that dietary 3-CQA supplementation improved the growth performance, nutrients digestibility in weaned pigs. The beneficial effects of 3-CQA supplementation on growth and intestinal functions suggested that it could serve as a natural potent substitute for antibiotics.

Influences of wheat bran fiber on growth performance, nutrient digestibility, and intestinal epithelium functions in Xiangcun pigs.

Dietary fiber (DF) has long been looked as an essential "nutrients" both for animals and humans as it can promote the intestinal tract development and modulate the intestinal epithelium functions and the gut microbiota. This study was conducted to investigate the influences of wheat bran fiber (WBF) on growth performance and intestinal epithelium functions in Xiangcun pigs. Twenty Xiangcun pigs with 60 days of age were divided to two groups and exposed to a basal diet (BD) or BD containing 4.3% wheat bran fiber (WFD). WFD improved the average daily gain (ADG) and feed-to-gain ratio (F:G) (p < 0.01). Moreover, WFD lowered the serum triglyceride (TC), d-lactate, and malonicdialdehyde (MDA) concentrations, but significantly improved the glutathione (GSH) activity and total antioxidant capacity (T-AOC) (p < 0.05). Interestingly, WFD observably improved the villus height (VH) and the villus height to crypt depth ratio (V/C) in the small intestine (p < 0.05). The jejunal sucrase and ileal maltase activities were higher in the WFD group (p < 0.05). WFD markedly elevated the tight junction protein ZO-1 and claudin-1 expression levels in the jejunum and ileum (p < 0.05). The sodium/glucose co-transporter 1 (SGLT1), glucose transporter 2 (GLUT2), and fatty acid transport proteins 4 (FATP-4) expression levels in jejunum and ileum were also elevated under WFD (p < 0.05). WFD decreased the IL-6 impression level in the duodenum and ileum, but significantly increased the IL-10 expression levels in jejunum and ileum (p < 0.05). Moreover, WFD reduced the abundance of E. coli, but elevated the abundances of beneficial microorganisms (e.g. Lactobacillus and Bacillus) and the production microbial metabolites (e.g. propionic acid and butyrate acid) in the cecum (p < 0.05).

The effect of dietary Yucca schidigera extract supplementation on productive performance, egg quality, and gut health in laying hens with Clostridium perfringens and coccidia challenge.

Yucca schidigera extract (YSE) is a green feed additive that is known to reduce toxic gas emissions and promote intestinal health in animal production. This study investigated the potential of dietary YSE supplementation to mitigate the negative effect of Clostridium perfringens and coccidia infection on productive performance and gut health in laying hens. A total of 48 Lohmann gray laying hens (35 wk of age) were randomly allotted to 1 of 2 groups (n = 24) fed with either a basal diet or a YSE-supplemented diet for 45 d. From d 36 to 45, half of the hens in each group were orally administrated with Clostridium perfringens type A and coccidia. This challenge impaired productive performance and egg quality (P < 0.05), destroyed jejunal morphology and functions (P < 0.05), induced jejunal epithelial cell apoptosis (P < 0.05), and downregulated the antioxidant capacity and Nrf2 pathway expression of jejunal mucosa (P < 0.05) in laying hens. Supplementing YSE in the laying hen diet, to some extents, improved productive performance and egg quality (P < 0.05), and alleviated the effect of challenge on morphology, functions, cell apoptosis, and antioxidant capacity in the jejunum (P < 0.05). Overall, the results suggested that dietary YSE supplementation might mitigate the negative effects of Clostridium perfringens and coccidia infection on gut health, and thereby improve the productive performance and egg quality of laying hens, possibly through enhancing the antioxidant capacity of the jejunum.

Retinoic acid protects against lipopolysaccharide-induced ferroptotic liver injury and iron disorders by regulating Nrf2/HO-1 and RARß signaling.

Acute liver injury (ALI) can progress to severe liver diseases, making its prevention and treatment a focus of research. Retinoic acid (RA) has been shown to have anti-oxidative and iron-regulatory effects on organs. In this study, we investigated the effect of RA on lipopolysaccharide (LPS)-induced ALI in both in vivo and in vitro experiments. We found that RA significantly reduced LPS-induced serum iron and red blood cell-associated disorders, as well as decreased serum ALT and AST levels. RA also reversed the accumulation of non-heme iron and labile iron in LPS-induced mice and hepatocytes by increasing the expression of FTL/H and Fpn. Furthermore, RA inhibited tissue reactive oxygen species (ROS) and malondialdehyde (MDA) production and improved the expression of Nrf2/HO-1/GPX4 in mice and Nrf2 signaling in hepatocytes. In vitro experiments employing RAR agonists and antagonists have revealed that retinoic acid (RA) can effectively inhibit cell ferroptosis induced by lipopolysaccharide (LPS), erastin, and RSL3. The mechanism underlying this inhibition may involve the activation of retinoic acid receptors beta (RARß) and gamma (RARγ). Knocking down the RARß gene in Hepatocytes cells significantly diminished the RA's protective effect, indicating that the anti-ferroptotic role of RA was partially mediated by RARß signaling. Overall, our study demonstrated that RA inhibited ferroptosis-induced liver damage by regulating Nrf2/HO-1/GPX4 and RARß signaling.

Dietary ferulic acid supplementation improves antioxidant capacity and lipid metabolism in liver of piglets with intrauterine growth retardation.

Intrauterine growth retardation (IUGR) can result in early liver oxidative damage and abnormal lipid metabolism in neonatal piglets. Ferulic acid (FA), a phenolic compound widely found in plants, has many biological functions, such as anti-inflammation and anti-oxidation. Thus, we explored the effects of dietary FA supplementation on antioxidant capacity and lipid metabolism in newborn piglets with IUGR. In the study, 24 7-day-old piglets were divided into three groups: normal birth weight (NBW), IUGR, and IUGR + FA. The NBW and IUGR groups were fed formula milk as a basal diet, while the IUGR + FA group was fed a basal diet supplemented with 100 mg/kg FA. The trial lasted 21 days. The results showed that IUGR decreased absolute liver weight, increased transaminase activity, reduced antioxidant capacity, and disrupted lipid metabolism in piglets. Dietary FA supplementation enhanced absolute liver weight, reduced serum MDA level and ROS concentrations in serum and liver, markedly increased serum and liver GSH-PX and T-SOD activities, decreased serum HDL-C and LDL-C and liver NEFA, and increased TG content and HL activity in the liver. The mRNA expression related to the Nrf2-Keap1 signaling pathway and lipid metabolism in liver were affected by IUGR. Supplementing FA improved the antioxidant capacity of liver by down-regulating Keap1 and up-regulating the mRNA expression of SOD1 and CAT, and regulated lipid metabolism by increasing the mRNA expression level of Fasn, Pparα, LPL, and CD36. In conclusion, the study suggests that FA supplementation can improve antioxidant capacity and alleviate lipid metabolism disorders in IUGR piglets.

Interferon-λ3 alleviates intestinal epithelium injury induced by porcine rotavirus in mice.

Interferons are a group of glycoproteins that are expressed in various cell types in their inflammatory responses to infections. In this study, we explored the protective effects of porcine interferon-λ3 (PIFN-λ3) on intestinal inflammation and injury in mice induced by porcine rotavirus (PRV). BALB/c mice were administrated by PIFN-λ3 or phosphate buffer solution (PBS) for three days prior to PRV infection. We show that PRV infection caused acute inflammatory responses in mice, as indicated by increases in serum concentrations of inflammatory cytokines such as the interlukin-1ß (IL-1ß), interlukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) (P < 0.05). However, PIFN-λ3 administration not only decreased their concentrations but also elevated the concentrations of immunoglobulin (Ig) M and IgG in the PRV challenged mice (P < 0.05). PRV infection significantly decreased the jejunal villus height and the ratio of villus height to crypt depth (V/C); however, PIFN-λ3 treatment significantly elevated the villus height and the abundance of tight junction protein ZO-1 in the jejunum (P < 0.05). Moreover, PIFN-λ3 decreased the replication of PRV in the jejunal epithelium, but significantly increased the abundance of sIgA and the activities of maltase and sucrase in the PRV-challenged mice (P < 0.05). Interestingly, PIFN-λ3 elevated the expression levels of sodium/glucose cotransporter 1 (SGLT1) and mucin 2 (MUC2) in the PRV-challenged mice (P < 0.05). Moreover, PIFN-λ3 significantly increased the expression levels of IL-10, signal transducer and activator of transcription 1 (STAT1), and critical interferon-stimulated genes such as the 2'-5' oligoadenylate synthetase-like 1 (OASL1), interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) and radical S-adenosyl methionine domain containing 2 (RSAD2) in the jejunum upon PRV infection (P < 0.05). The anti-virus and anti-inflammatory effect of PIFN-λ3 should make it an attractive candidate to prevent various pathogen-induced bowel diseases.

Yeast hydrolysate attenuates lipopolysaccharide-induced inflammatory responses and intestinal barrier damage in weaned piglets.

BACKGROUND: Intestinal inflammation is the main risk factor causing intestinal barrier dysfunction and lipopolysaccharide (LPS) can trigger inflammatory responses in various eukaryotic species. Yeast hydrolysate (YH) possesses multi-biological effects and is received remarkable attention as a functional ingredient for improving growth performance and promoting health in animals. However, there is still inconclusive on the protective effects of dietary YH supplementation on intestinal barrier of piglets. This study was conducted to investigate the attenuate effects of YH supplementation on inflammatory responses and intestinal barrier injury in piglets challenged with LPS. METHODS: Twenty-four piglets (with an average body weight of 7.42 ± 0.34 kg) weaned at 21 days of age were randomly assigned to one of two dietary treatments (12 replications with one pig per pen): a basal diet or a basal diet containing YH (5 g/kg). On the 22nd d, 6 piglets in each treatment were intraperitoneally injected with LPS at 150 µg/kg BW, and the others were injected with the same amount of sterile normal saline. Four hours later, blood samples of each piglet were collected and then piglets were euthanized. RESULTS: Dietary YH supplementation increased average daily feed intake and average daily gain (P < 0.01), decreased the ratio of feed intake to gain of piglets (P = 0.048). Lipopolysaccharide (LPS) injection induced systemic inflammatory response, evidenced by the increase of serum concentrations of haptoglobin (HP), adrenocorticotropic hormone (ACTH), cortisol, and interleukin-1ß (IL-1ß). Furthermore, LPS challenge resulted in inflammatory intestinal damage, by up-regulation of the protein or mRNA abundances of tumor necrosis factor-α (TNF-α), IL-1ß, toll-like receptors 4 (TLR4) and phosphor-nuclear factor-κB-p65 (p-NFκB-p65) (P < 0.01), and down-regulation of the jejunal villus height, the protein and mRNA abundances of zonula occludens-1 (ZO-1) and occludin (OCC; P < 0.05) in jejunal mucosa. Dietary YH supplementation decreased the impaired effects of ACTH, cortisol, HP, IL-1ß and diamine oxidase in serum (P < 0.05). Moreover, YH supplementation also up-regulated the jejunal villus height, protein and mRNA abundances of ZO-1 and OCC (P < 0.05), down-regulated the mRNA expressions of TNF-α and IL-1ß and the protein abundances of TNF-α, IL-1ß, TLR4 and p-NFκB-p65 in jejunal mucosa in LPS-challenged pigs (P < 0.01). CONCLUSION: Yeast hydrolysate could attenuate inflammatory response and intestinal barrier injury in weaned piglets challenged with LPS, which was associated with the inhibition of TLR4/NF-κB signaling pathway activation.