This study investigated the effects of proline on intestinal injury in piglets infected with porcine epidemic diarrhea virus (PEDV). Twenty-eight 7-day-old piglets were assigned to four groups: control (CON), proline (Pro), PEDV, and Pro + PEDV. Piglets in the Pro and Pro + PEDV groups received oral proline (500 mg/kg body weight) for 7 days. During the last 3 days, piglets in the PEDV and Pro + PEDV groups were inoculated with PEDV. Under PEDV infection, proline administration increased villus height and the villus height/crypt depth ratio in both the jejunum and ileum, and villus width and villus surface area in the ileum. Proline increased PEDV N protein abundance and interferon β (IFN-β) mRNA level in both intestinal segments, suppressed downstream antiviral genes in infected piglets, but upregulated these genes in the jejunum of uninfected piglets. Proline further increased interleukin 1β (IL-1β) concentrations and the expression of inflammation-related genes in the jejunum of infected piglets. Under PEDV infection, proline increased superoxide dismutase (SOD) activity in serum and jejunum, while reducing jejunal H2O2 concentration. Furthermore, proline downregulated genes related to lipid synthesis and ion transport in the jejunum of infected piglets. Transcriptomic and RT-qPCR analyses supported these findings, indicating that proline enhanced immune defense while suppressing lipid metabolism. In conclusion, proline alleviated PEDV-induced intestinal injury by improving villus morphology and enhancing antiviral and antioxidant defenses. However, it promoted viral replication and inflammation, while suppressing lipid metabolism. The multifaceted effects of proline on PEDV infection indicate its practical use warrants careful consideration.

Porcine epidemic diarrhea virus (PEDV) causes severe intestinal injury and economic losses in the pig industry. Arginine (Arg) promotes barrier repair and immune regulation, but its effects on PEDV-induced damage are unclear. This study aimed to investigate whether Arg could alleviate intestinal injury in PEDV-infected piglets. Thirty-two 7-day-old piglets were randomly divided into four groups: Control, Arg, PEDV, and PEDV+Arg. Piglets in the Arg and PEDV+Arg groups were orally administered 400 mg/kg BW Arg from Day 5 to Day 11. On Day 11, PEDV-infected piglets were orally challenged with the virus at a dosage of 1 × 105.5 TCID₅₀ per individual. On Day 14, tissue samples were collected after slaughter. PEDV infection markedly reduced villus height (VH) in the duodenum, jejunum, and ileum, increased crypt depth (CD), decreased plasma D-xylose concentration, and elevated diamine oxidase (DAO) activity, whereas Arg supplementation restored VH, decreased CD in the duodenum and jejunum, increased D-xylose, and reduced DAO activity. Arg also enhanced villin, occludin, and claudin-1 expression, indicating improved barrier integrity. Interestingly, Arg could promote PEDV replication in the small intestine. However, Arg reduced IL-1β, REG3G, and iNOS expression, while upregulating antiviral genes IFITM3, MX1, and DHX58 in the jejunum. Transcriptomic and proteomic analyses indicated that Arg administration may enhance interferon signaling cascades through the RIG-I-like receptor signaling pathway. In conclusion, our results show that Arg exhibits multifaceted effects upon PEDV infection. Although it increases PEDV replication, Arg could enhance intestinal barrier function, attenuate intestinal inflammatory responses, and alleviate PEDV-induced intestinal injury in piglets.

Porcine epidemic diarrhea (PED) is a severe viral disease caused by the porcine epidemic diarrhea virus (PEDV), leading to huge economic losses in the swine industry. Identifying therapeutic targets has long been a critical challenge in preventing and controlling PED through nutritional interventions. In the present study, 100 seven-day-old crossbred (Duroc × Landrace × Large White) healthy piglets from seven independent trials were selected for the experiment. The transcriptomics, proteomics, and metabolomics analyses were conducted on the small intestine and blood of piglets infected with PEDV, and the combined multiple batches of data were subsequently subjected to integrated analysis. Our findings revealed that PEDV infection significantly affected intestinal cell metabolism, especially lipid metabolism. Among those, sphingolipid and lysophospholipid metabolism could be potential pathways for preventive and therapeutic interventions. Additionally, retinol metabolism, mineral absorption, amino acid metabolism, and pyrimidine metabolism were remarkably altered following PEDV infection. Subsequently, candidate hub genes involved in the core pathways, such as apolipoprotein C3 (APOC3), cytochrome P450 family 3 subfamily A member 22 (CYP3A22), and intestinal alkaline sphingomyelinase (ENPP7), were identified and validated. In conclusion, the present study suggests that PEDV infection leads to the reprogramming of enterocyte lipid metabolism. Furthermore, manipulating lipid metabolism may influence the outcome of viral infection, highlighting potential targets for preventive and therapeutic interventions in managing viral infections. IMPORTANCE:Porcine epidemic diarrhea (PED) is a severe viral disease caused by the porcine epidemic diarrhea virus (PEDV), leading to huge economic losses in the swine industry. Identifying therapeutic targets has long been a critical challenge in preventing and controlling PED through nutritional interventions. The present study suggests that PEDV infection leads to the reprogramming of enterocyte lipid metabolism. Furthermore, manipulating lipid metabolism may influence the outcome of viral infection. The study also highlights potential targets for preventive and therapeutic interventions in managing viral infections.

This study investigated the protective effects of glyceryl monooleate (GM) against porcine epidemic diarrhea virus (PEDV)-induced intestinal injury in neonatal piglets. In vitro assays revealed that GM inhibited PEDV replication. Twenty-four seven-day-old piglets were assigned to four groups: control, GM, PEDV, and PEDV + GM. Piglets received 100 mg/kg GM from days 4–10 and were challenged with 10⁶ TCID50 PEDV on day 8. Samples collected on day 11 were analyzed for intestinal morphology, oxidative stress, inflammation, and microbiota composition. PEDV infection significantly impaired growth performance and disrupted intestinal integrity, as shown by reduced villus height, increased crypt depth, and decreased plasma D-xylose levels (P < 0.05). It also induced oxidative stress, elevated plasma malondialdehyde (MDA), hydrogen peroxide (H2O2), and myeloperoxidase (MPO) levels, and activated inflammatory responses through the TNF-α signaling pathway, increasing interferon regulatory factor 7 (IRF7), myxovirus resistance protein 1 (MX1), interferon-stimulated gene 15 (ISG15), and tumor necrosis factor-α (TNF-α) expression (P < 0.05). Gut microbiota analysis revealed an increased abundance of Fusobacterium, Collinsella, and Campylobacter, and a reduction in Bacteroidetes and Allelobacterium (P < 0.05). GM supplementation alleviated PEDV-induced intestinal injury by improving villus height, reducing crypt depth, and enhancing antioxidant capacity through increased catalase (CAT) and total superoxide dismutase (T-SOD) activities (P < 0.05). It also suppressed viral replication and inflammatory signaling, downregulating TNF-α–related genes and cytokines (IRF7, MX1, ISG15, 2’-5’-oligoadenylate synthetase like (OASL), TNF-α, and CXCligand2 (CXCL2) expression, and plasma interleukin-1β (IL-1β) and TNF-α concentrations), and restored microbial balance by reducing pathogenic bacteria such as Escherichia coli and Shigella (P < 0.05). Collectively, these results indicate that GM protects against PEDV-induced intestinal damage by inhibiting viral replication, enhancing antioxidant defenses, modulating inflammatory pathways, and maintaining gut microbial homeostasis.

The protective effect of Compound terminalia chebula extract (HL) against colonic injury induced by Porcine epidemic diarrhea virus (PEDV) infection in neonatal piglets remains unclear. This study aimed to evaluate the mitigating effects of HL on PEDV-induced colonic injury and elucidate the underlying mechanisms. Eighteen 7-day-old Duroc × Landrace × Large White piglets (2.58 ± 0.05 kg) were randomly assigned to three groups (n = 6/group): CON (blank control), PEDV (infected), and HL + PEDV (HL-supplemented + infected). The 11-day trial included 3 days of acclimatization (days 0-3) and an 8-day experimental period (days 4-11). HL (10 mg/kg BW) was orally administered daily to the HL + PEDV group. On day 8, PEDV and HL + PEDV groups were challenged with 3 mL PEDV (3 × 106 TCID50/mL), while CON received Dulbecco's Modified Eagle Medium (DMEM). All piglets were euthanized on day 11 for colonic tissue collection. Results indicated that PEDV infection induced colonic injury, manifested by a significant increase in crypt depth and disruption of intestinal homeostasis. This was evidenced by impaired barrier integrity (upregulation of matrix metalloproteinase-7 gene [MMP7] and matrix metalloproteinase 13 gene [MMP13], mucus disorganization (elevation of mucin 5AC gene [MUC5AC]), oxidative stress (reduced catalase [CAT] activity and increased malondialdehyde [MDA] levels in serum and colon), and inflammation (upregulation of regenerative islet-derived protein 3γ gene [REG3G], S100 calcium-binding protein A8/A9 gene [S100A8/A9], and interleukin-1β gene [IL-1β]). Additionally, PEDV impaired colonic ion transport by downregulating calcium channel genes (Transient Receptor Potential Cation Channel Subfamily V Member 6 gene [TRPV6], Transient Receptor Potential Cation Channel Subfamily M Member 6 gene [TRPM6]). Notably, HL supplementation effectively reversed these adverse effects. HL restored colonic morphology, increased CAT activity, reduced MDA accumulation, and suppressed inflammatory gene expression. Furthermore, HL modulated the expression of genes involved in water and ion transport upregulating Aquaporin 7 gene (AQP7), Chloride Channel Accessory 4 gene (CLCA4), Sodium-Hydrogen Exchanger 3 gene (NHE3), Transient Receptor Potential Vanilloid 6 (TRPV6), and Transient Receptor Potential Melastatin 6 gene (TRPM6) and significantly inhibited PEDV replication, as indicated by the downregulation of the transcription levels of PEDV membranegene (M), nucleocapsid gene (N), and spike gene (S). Taken together, HL alleviates PEDV-triggered colonic tissue damage in suckling piglets via improving colonic antioxidant capacity, mitigating inflammatory response, partially regulating intestinal barrier and ion/water transport-related genes, and downregulating the transcription of PEDV structural genes at molecular and histological levels.

The preventive effect of leucine (Leu) against colonic damage in piglets infected with porcine epidemic diarrhea virus (PEDV) was examined in this study. Three groups (n = 6) were randomly assigned to eighteen 7-day-old Du-roc x Landrace x Large piglets (body weight [BW] = 2.58 +/- 0.05 kg): Control, PEDV-infected (PEDV), and Leu-supplemented + PEDV-infected (Leu + PEDV). Following a three-day period of acclimatization, the Leu + PEDV group was given Leu (400 mg/kg BW) orally every day. On day eight, the PEDV and Leu + PEDV groups were challenged with PEDV, while the Control group was given Dulbecco's Modified Eagle's Medium. Colonic tissues were collected on day 11. PEDV infection induced severe colonic damage by an increase in crypt, disrupting intestinal homeostasis, including impaired barrier integrity (matrix metalloproteinase-7 and matrix metalloproteinase-13 upregulation), mucus disorganization (mucin 5AC elevation), oxidative stress (reduced catalase activity and increased malondialdehyde levels), inflammation, electrolyte imbalance and enhanced viral replication. Leu supplementation reversed these injuries by alleviating oxidative stress, suppressing inflammation, inhibiting viral replication and stabilizing ion homeostasis. This study provides a scientific basis for Leu as a nutritional intervention to alleviate PEDV-induced colonic damage in piglets.

Probiotics have great potential in maintaining intestinal health and ensuring the growth performance of broiler chickens, while the effects of Bacillus velezensis (BV) have not yet been fully characterized. In the present study, a necrotic enteritis model was established based on the combined infection of coccidia and Clostridium perfringens (CCP), and the effects of dietary supplementation with BV on growth performance and intestinal health were investigated. Our outcomes showed that dietary supplementation with BV contributed to alleviating the negative effects of CCP on the growth performance. Additionally, the ratio of ileal villus height to crypt depth, the levels of D-xylose and lysozyme in serum, as well as that of secretory immunoglobulin A (sIgA) in ileum were decreased, and the activity of diamine oxidase (DAO) was elevated with CCP challenged (P< 0.05). In addition, the level of ileal malondialdehyde (MDA), transcriptional levels of IL-1β and interferon-γ (IFN-γ) were up-regulated, correspondingly, the ileal total antioxidant capacity (T-AOC) and the mRNA levels of transforming growth factor-β (TGF-β), lysozyme (LYZ), Claudin-1, and Mucin-2 were down-regulated with CCP challenged (P< 0.05). Interestingly, the BV-supplemented diet was able to alleviate the above-mentioned negative effects of CCP on birds. The results of intestinal microbiota sequencing and association analysis further revealed that dietary supplementation with BV helped to enhance the energy utilization efficiency of the intestinal flora and might alleviate the impaired intestinal function of birds challenged with CCP by reshaping intestinal flora, especially through modulating the relative abundance of Clostridium. In conclusion, the diet supplemented with BV enhances the intestinal health of broiler chickens challenged with necrotic enteritis via reshaping the structure and function of the intestinal flora.

This study aims to investigate the effects of low-energy diets (LE) supplemented with Lactobacillus reuteri postbiotics (HSY) on growth performance and intestinal health of broiler chickens. A total of 2400 one-day-old Ross 308 broiler chicks with an average initial body weight of 46.10 ± 0.04 g were randomly assigned to a 2 × 2 factorial arrangement of treatments with 12 pens and 50 broiler chickens/pen for 39 days. Treatments were (1) CTR (basal diet), (2) LE (CTR-70 kcal ME/kg), (3) HSY (CTR + 0.5 kg/t HSY), and (4) LEHSY (LE + 0.5 kg/t HSY). LE increased the feed conversion ratio (FCR) of broilers (p = 0.03) without altering ADG, ADFI, and final BW. Supplementation with HSY significantly reduced the FCR of broilers (p = 0.001). HSY upregulated the activities of amylase and trypsin in jejunal digesta (p < 0.01). Furthermore, LE upregulated the expression of intestinal barrier-related genes such as Mucin-2, Claudin-1 and Occludin, and HSY upregulated the expression of Claudin-1 (p < 0.05). LE upregulated the expression of nutrient transport carriers such as SGLT1 and TRPV6 (p < 0.01), and HSY upregulated the expression of TRPV6 (p < 0.01). LE upregulated the expression of immune-related genes such as MHC-II (p = 0.002), and HSY upregulated the expression of IFN-γ, IL-10, and TGF-β (p < 0.05). LE and HSY both downregulated the expression of intestinal lipid metabolism-related genes like ACC, while upregulating the expression of FABP4 (p < 0.05). 16S rRNA sequencing showed that the HSY increased the Chao1 index of the jejunal microbiota and enriched beneficial bacteria such as Lactobacillus salivarius and Lactobacillus avium. LE and HSY both increased the concentrations of propionic and butyrate (p < 0.05). In summary, HSY can improve gut health and mitigate the negative impact of low-energy treatment on broiler growth performance by increasing the content of endogenous enzymes in the jejunum, improving gut microbiota structure, and increasing the content of short-chain fatty acids in the jejunum.

Porcine epidemic diarrhea virus (PEDV) imposes substantial economic losses on the global swine industry owing to its high pathogenicity and transmissibility. Although arginine (Arg) is known to support the integrity of intestinal barrier, it is not clear whether Arg can alleviate intestinal injury induced by PEDV. A total of 32 healthy 7-day-old piglets were randomly assigned to four groups (Control, Arg, PEDV, PEDV + Arg; eight replicates per group). From day 5, piglets in the Arg and PEDV + Arg groups were orally administered Arg at 400 mg/kg body weight until day 11; then, PEDV (1 × 105.5 TCID50) was given orally for two PEDV-infected groups. On day 14, all piglets were slaughtered to obtain blood and intestine samples for further analysis. The results showed that PEDV infection significantly reduced T-SOD and CAT activities in plasma and intestine while elevating MPO levels. Arg supplementation restored T-SOD (plasma, duodenum, ileum), CAT (plasma, ileum), and GSH-Px (jejunum, ileum) activities and reduced MDA (jejunum) content in PEDV-infected piglets. Hematological analysis showed Arg alleviated PEDV-induced increases in MCV and RDW-SD, and significantly elevated MCHC. The real-time quantitative PCR analysis demonstrated that Arg further enhanced PEDV structural genes (M, N, S) expression in the duodenum, ileum, and colon. Concurrently, Arg significantly up-regulated interferon-stimulated genes (MX1, OASL, ISG15, IFITM3) in the ileum, IRF7 in the duodenum and colon, and IFN-β in the ileum. Arg also down-regulated the pro-inflammatory cytokines IL-6 and CXCL2 and the antimicrobial peptide REG3G in the colon, while up-regulating the tissue repair gene MMP13 in the ileum. In conclusion, oral Arg exhibits a unique dual role: it promotes PEDV replication to a certain extent while significantly enhancing antioxidant capacity, strengthening intestinal antiviral immunity, and attenuating intestinal inflammation. These findings highlight Arg’s role in promoting disease tolerance and offer a novel perspective for nutritional intervention strategies against PEDV infection.

Porcine epidemic diarrhea virus (PEDV) is a major pathogen causing severe diarrhea and intestinal damage in piglets. Monolaurin (GML) and tributyrin (TB) are well-documented functional lipids with intestinal health benefits, but their combined efficacy against PEDV infection remains unclear. The present study first investigated the anti-PEDV effect of GML, TB, and their mixtures using PEDV-infected Vero cells. Then, the effects of a microencapsulated TB-GML complex (PE) were evaluated in PEDV-infected piglets, focusing on its protective mechanisms. Vero cells were simultaneously treated with PEDV and graded concentrations of GML (20-40 μmol/L), TB (0.25-0.50 mmol/L), or their combinations to determine for synergistic antiviral effects. In vivo, a total of 30 piglets (2.49 ± 0.38 kg), 7-d-old, were randomly assigned to three groups: negative control (NC), PEDV, and PE + PEDV. After a 3-d adaptation period, piglets in the PE + PEDV group received an oral dose of PE at 100 mg/kg body weight for 7 consecutive days. On d 8, piglets in the PEDV and PE + PEDV groups were orally inoculated with 1 × 106 50% tissue culture infective dose (TCID50) of PEDV per piglet. The experiment lasted for 11 d. The results showed that 40 μmol/L GML alone, or 0.25 mmol/L TB combined with 20-40 μmol/L GML, suppressed virus replication (P = 0.023). The PE administration improved villus morphology and increased expression of genes involved in water and ion transport in the jejunum, including AQP10, KCNJ13, NHE2, and NHE3 (P < 0.05). Additionally, PE reduced serum interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) levels, and downregulated jejunal relative mRNA expression of inflammation-related genes, mainly IL-8, IL-1β, and CXCL2 (P < 0.05). The PE reversed the enhanced antioxidant stress response in the jejunum by reducing total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and myeloperoxidase (MPO) activities (P < 0.05). The PE inhibited PEDV replication, downregulated relative mRNA expression of IFN-β and its downstream genes, and reduced protein abundance of PEDV-N (P < 0.05). Transcriptomic and quantitative real-time PCR (RT-qPCR) analyses revealed that PE restored lipid metabolic homeostasis by balancing lipogenesis, lipid transport, and fatty acid β-oxidation. Moreover, PE increased the abundance of Proteobacteria, Bacteroidota, Bacteroides, and Halomonas, while decreasing the abundance of Firmicutes and Lactobacillus. In conclusion, PE mitigated inflammation, enhanced antioxidant and antiviral capacities, while alleviating disruptions in water and ion transport, lipid metabolism, and gut microbiota.

The impact of ZnO as a feed additive on growth-performance and intestinal function of Enterotoxigenic Escherichia coli (ETEC) K88-infected piglets remains unclear. Fecal scores of piglets in ETEC group were significantly increased compared to control group. ETEC K88 significantly damages the small intestine, including a reduction in villus height in the jejunum, duodenum, and ileum, and a decrease in total superoxide dismutase activity in the jejunum and catalase activity in the ileum and jejunum. Compared to control group, ETEC K88 infection significantly elevated the mRNA level of gene IL-1β and the level of ileal epithelial cell apoptosis. ZnO administration significantly alleviated these negative effects and improved the antioxidative capability of the ileum. Moreover, ZnO supplementation alleviated the imbalance of gut microbiota by restoring the reduced amount of Enterococcus and Lactobacillus in the jejunum, Clostridium in the ileum, and Lactobacillus in the cecum, as well as the increased amount of total eubacteria in the ileum and Enterococcus in the cecum induced by the ETEC K88 infection. In conclusion, ZnO administration can reduce the diarrhea of piglets infected with ETEC K88 by reducing the structural damage of the intestine, attenuating intestinal oxidative stress and epithelial cell apoptosis, and modulating the gut microbiota.

The present study aimed to explore the effects of dietary phloretin (PT) on growth performance, immune response, and intestinal function in broilers with necrotic enteritis (NE). A total of 288 1-day-old Arbor Acres chicks were assigned to 3 groups, with 8 replicates per group and 12 chicks per replicate. Over 6 weeks, birds were fed a basal diet or the same diet supplemented with 200 mg/kg phloretin. Birds in the challenged groups were inoculated with coccildia during d 7 to 9 and Clostridium perfringens(CP) during d 14 to 18. Results showed that CP and coccidia challenge reduced the average daily gain and average daily feed intake, increased the feed conversion ratio of broilers, induced inflammation and oxidative stress, and inhibited mRNA expression levels for genes associated with intestinal barrier and nutrient transporters (P < 0.05). PT addition to the feed improved growth performance at early phase improved intestinal morphology, and elevated antioxidant capacity via increasing the activity of total antioxidant capacity and superoxide dismutase in the ileum in broilers with necrotic enteritis (P < 0.01). Dietary PT regulated the intesetinal immune function as observed by the increases in the content of secretory IgA in the ileum and decreased cytokines (Interleukin-1β, Interleukin-10) (P < 0.05). Moreover, NE infection significantly disrupted the balance of intestinal flora, and led to a lower level of short-chain fatty acids such as butyric acid concentration in the ileum, while PT improved the microbiota structure, and increased the intestinal acetic acid and butyric acid concentration (P < 0.001). Furthermore, metabolomics analysis indicated PT treatment improve plant secondary metabolites contents like phloretin 2'-o-glucuronide. Additionally, we observed a significant positive correlation among PT, Ligilactobacillus and butyric acid, and a positive correlation between Ligilactobacillus and plant secondary metabolites. Overall, PT supplementation could improve growth performance and ameliorate intestinal injury in broilers with necrotic enteritis by enhancing the antioxidant capacity and immune function, regulating intestinal flora structure and producing plant secondary metabolites.

This study aimed to assess whether dietary supplementation with probiotics could alleviate intestinal injury in lipopolysaccharide (LPS)-challenged piglets. Healthy weaned piglets were randomly allocated to four individual groups (n = 6): (1) a control group; (2) an LPS group; (3) an LPS + Lactobacillus group; and (4) an LPS + Bacillus group. The control and LPS groups received a basal diet, while the probiotic groups were provided with the same basal diet supplemented with 6 × 106 cfu/g of Lactobacillus casei (L. casei) or a combination of Bacillus subtilis (B. subtilis) and Bacillus licheniformis (B. licheniformis) at a dosage of 3 × 106 cfu/g, respectively. On day 31 of the trial, overnight-fasted piglets were killed following the administration of either LPS or 0.9% NaCl solution. Blood samples and intestinal tissues were obtained for further analysis several hours later. The results indicate that dietary supplementation with probiotics significantly exhibited health-promoting effects compared with the control group and effectively reduced LPS-induced histomorphological damage to the small intestine, impairments in barrier function, and dysregulated immune responses via modulation of enzyme activity and the expression of relevant genes, such as nuclear factor-kappa B (NF-κB), interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 10 (IL-10), claudin-1, nuclear-associatedantigenki-67 (Ki-67), and β-defensins-1 (pBD-1). Collectively, these results suggest that dietary supplementation with probiotics could alleviate LPS-induced intestinal injury by enhancing the immunity and anti-inflammatory responses in piglets. Our research provides a theoretical basis for the rational application of probiotics in the future.

Porcine epidemic diarrhea virus (PEDV) infection poses a significant challenge to the swine industry, with limited effective control measures available. Poria cocos polysaccharides (PCP) is the primary active ingredient of Poria cocos, and has been demonstrated to show beneficial effects on intestinal damage in previous studies. However, its mechanism has not been fully understood. In the present study, 18 seven-day-old piglets were divided into 3 groups: Control group, PEDV group, and PCP + PEDV group. After three days of adaptation, piglets in the PCP + PEDV group were orally administered 10 mg/kg body weight/d PCP from d 4 to 10. On d 8, piglets were orally administered with PEDV at the dose of 104.5 TCID50/piglet. This study aimed to investigate the potential effects of PCP on PEDV-induced intestinal injury and explored the underlying mechanisms. The results showed that PCP administration effectively alleviated diarrhea, reduced PEDV replication in the small intestine and colon of piglets, and significantly improved intestinal mucosal morphology. Specifically, PCP increased the villus height in both the jejunum and ileum and increased the villus height to crypt depth ratio in the ileum (P < 0.05). Improved intestinal function was further evidenced by elevated plasma D-xylose levels and decreased diamine oxidase activity (P < 0.05). Transcriptomic and proteomic analyses revealed that lipid metabolism is a key pathway regulated by PCP during PEDV infection. Notably, PCP significantly upregulated sphingolipid metabolism-related genes, including ectonucleotide pyrophosphatase/phosphodiesterase family member 7 and N-acylsphingosine amidohydrolase 2. Metabolomic analysis revealed that PCP primarily modulated the levels of plasmanylphosphoethanolamine, lysophosphatidylcholine, and carnitine. Additionally, PCP reversed the expression of key genes involved in fatty acid uptake, intracellular lipid transport, and fatty acid synthesis, such as fatty acid binding protein 2, fatty acid transport protein 4, apolipoprotein B, apolipoprotein C3, fatty acid synthase, long-chain fatty acyl CoA synthetase 3, lipoprotein lipase and acyl-CoA thioesterases 12 (P < 0.05). These findings demonstrate that PCP mitigates PEDV-induced intestinal injury by modulating lipid metabolism and highlight its potential as a dietary supplement for enhancing anti-PEDV defenses and promoting intestinal health in piglets.

This study investigated the protective effects of glycerol monooleate (GMO) against porcine epidemic diarrhea virus (PEDV)-induced intestinal injury in neonatal piglets. Twenty-four 7-day-old piglets were divided into four groups: CTRL, GMO, PEDV, and PEDV + GMO. From D 4–10, piglets in GMO groups received 100 mg/kg GMO supplementation. Piglets in PEDV–infected groups were challenged with 10⁶ TCID₅₀ PEDV per piglet on D 8. Blood and intestinal samples were collected from all piglets after euthanasia on D 11 to assess intestinal morphology, oxidative stress status, inflammatory response, and intestinal microbiota. PEDV infection significantly reduced average daily gain (ADG) during D 9–11 ( P < 0.05), impaired intestinal barrier function indicated by lower plasma D-xylose, increased duodenal crypt depth (CD) and decreased villus height (VH) and VH/CD ratios in duodenum, jejunum, and ileum. PEDV caused oxidative stress, elevating plasma and duodenum malondialdehyde (MDA) content, plasma hydrogen peroxide (H₂O₂) content, and myeloperoxidase (MPO) activity, while duodenum catalase (CAT) activity declined ( P < 0.05). PEDV activated systemic inflammation through TNF-α signaling pathway, indicated by upregulating IRF7 , MX1 , IFN-β , OASL , ISG15 , TNF-α , and CXCL2 mRNA, and elevating plasma IL-1β and TNF-α contents ( P < 0.05). Gut microbiota analysis revealed PEDV increased abundance of Fusobacterium , Collinsella , and Campylobacterota while reducing Bacteroidetes and Alloprevotella ( P < 0.05). GMO supplementation attenuated PEDV-induced intestinal injury, indicated by increasing ileal VH, reducing duodenum and ileum CD, and therefore improving ADG ( P < 0.05). GMO enhanced antioxidant capacity via increasing CAT in plasma and total superoxide dismutase (T-SOD) activities in duodenum and suppressing MDA in ileum and H₂O₂ levels in plasma and jejunum ( P < 0.05). GMO inhibited viral replication and modulated TNF-α signaling pathway, downregulating IRF7 , MX1 , ISG15 , OASL , TNF-α , and CXCL2 expression, reducing plasma IL-1β and TNF-α concentrations ( P < 0.05). In addition, GMO suppressed abundance of pathogenic bacteria such as Escherichia coli and Shigella spp ( P < 0.05). These findings demonstrate that GMO inhibits PEDV replication and alleviates PEDV-induced intestinal damage through multifaceted mechanisms: enhancing antioxidant capacity, mitigating inflammatory responses via TNF pathway regulation, and balancing gut microbiota.

The poor intestinal health induced by management, stress, or infection remains a substantial challenge restricting the rapid development of the pig industry. Some natural plant bioactive components (NPBCs) have garnered considerable interest owing to their multifarious benefits, including enhancing intestinal morphology, digestion and absorption, barrier function, immune function, and regulating the gut microbiota. However, there are critical factors, such as the lack of standardized production technologies, lower stability and bioavailability, and unclear mechanisms of NPBCs, severely limiting their feeding efficacy and their application in animal production. Here, we conducted a comprehensive review of the recent advances regarding the impacts of NPBCs on pig gut health. Additionally, we highlighted the key areas that warrant further in-depth investigation. Taken together, NPBCs could be green, safe, and effective feed additives by constructively overcoming their limitations, and they are expected to have broader applications in animal husbandry.

Soya saponins (SS) have the ability to improve the intestinal microbiota and enhance intestinal immune function. While, there are few reports on their application in broiler production. The present study was designed to investigate effects of dietary supplementary with SS on the intestinal health of birds challenged with coccidia (CC). 180 male and healthy Cobb 500 broiler chickens with unifrom body weight were randomly divided into 3 treatment groups, those groups were named as the control group (CTR), the coccidia challenged group (CC), and the SS treated group challenged with CC (SS+CC). There were 6 replicates in each group, and 10 birds in each replicate. Birds in the CTR and CC group were fed with the basic diet, and birds in the SS+CC group were fed with the basic diet supplemented with 200 mg/kg SS. The animal trial lasted for 21 days, on day 10 and 12, birds in the CC and SS+CC group were challenged with CC, and birds in the CTR group were treated with normal saline, samples were harvested on day 14, and the growth performance from day 1 to day 10 as well as from day 1 to day 21 were recorded. Outcomes showed that the body weight (BW), average daily weight gain (ADG) and average daily feed intake (ADFI) were descended, and the feed conversion ratio (FCR) was elevated with CC challenged (P < 0.05). The villi height (VH) and the ratio of VH to crypt depth (CD) in jejunum and ileum were decreased with CC challenged, as well as the levels of ileal secretory immunoglobulin A (sIgA) and acetic acid in the ileal chyme (P < 0.05). Additionally, the mRNA level of ileal occludin was down-regulated, the transcriptional levels of ileal IL-8, interferon-γ (IFN-γ), cysteine-dependent aspartate-specific protease-1 (Caspase-1), and induced NO synthase (i-NOS) were up-regulated with CC challenged (P < 0.05). Dietary supplementary with SS tended to improve the FCR from day 1 to day 10 (P = 0.06), and was able to alleviated the above-mentioned negative effects induced by CC. Interestingly, dietary supplementary with SS contributed to reshaping the structure of the intestinal microbiota, specifically, reshaping the abnormal changes in the abundance of Lactobacillus and Romboutsia in the ileal chyme challenged with CC (P < 0.05). It was worth mentioning that the relative abundance of Lactobacillus was positively correlated with the levels of short-chain fatty acids in the ileal chyme, and it of Romboutsia was positively correlated with the mRNA levels of ileal IL-8, IFN-γ, Caspase-1, and i-NOS (P < 0.05). In conclusion, dietary supplementary with SS alleviated the poor intestinal health of broilers caused by CC via reshaping the structure of the intestinal microbiota.

BACKGROUND:Porcine epidemic diarrhea virus (PEDV) poses a significant threat to the global pig industry. Niacin (NA) may play an important role in improving intestinal health in piglets. OBJECTIVE:The present study aimed to investigate the effects of NA supplementation on growth performance and intestinal health in young piglets infected with PEDV. METHODS:Forty 7-d-old healthy piglets were randomly assigned to 4 groups: control, NA, PEDV, and PEDV+NA. After 3 d of adaptation, piglets in the NA and PEDV+NA groups were orally administered NA at 30 mg/kg body weight from day 4 to 11. On day 9, piglets in the PEDV and PEDV+NA groups were orally inoculated with PEDV at a dose of 104.5 TCID50. On day 12, tissue samples were collected following euthanasia and exsanguination. Intestinal injury was confirmed by the determination of intestinal villus height (VH), crypt depth (CD), as well as plasma diamine oxidase (DAO) and D-xylose concentration. qPCR was performed to evaluate the viral load. Western blot analysis was employed to investigate the intestinal immune response. Data were analyzed by 2-way analysis of variance, with PEDV and NA as factors. RESULTS:NA administration improved average daily gain and mitigated intestinal injury in PEDV-infected piglets, as indicated by reduced CD and increased VH/CD ratios in the duodenum, jejunum, and colon, along with decreased plasma DAO levels (P < 0.05). NA significantly inhibited the expression of PEDV M and N genes in both the jejunum and ileum (P < 0.01). Moreover, NA reduced the protein abundance of interferon-stimulated genes, including interferon-stimulated gene 15 (ISG15), 2'-5'-oligoadenylate synthetase-like protein (OASL), and myxovirus resistance 1 (MX1), in the intestines of PEDV-infected piglets (P < 0.05). CONCLUSIONS:The results suggest that NA could inhibit viral replication and alleviate the intestinal injury in PEDV-infected piglets by regulating host immune responses.