Dietary Supplementation with Lysozyme-Cinnamaldehyde Conjugates Enhances Feed Conversion Efficiency by Improving Intestinal Health and Modulating the Gut Microbiota in Weaned Piglets Infected with Enterotoxigenic Escherichia coli.

This study aims to evaluate the efficacy of lysozyme-cinnamaldehyde conjugates (LC) as a potential alternative to antibiotics in treating piglets infected with enterotoxigenic Escherichia coli (ETEC). The results demonstrated that piglets fed with the LC diet exhibited lower rectal temperature and fecal scores at 9 h, 24 h, and 48 h post-ETEC challenge. Furthermore, LC supplementation led to significant improvements in the mechanical and immune barriers of the jejunum and ileum, as indicated by an increased villi-height-to-crypt-depth ratio (VCR) and the expression of tight junction proteins, mucin, and ß-defensins. Furthermore, the LC diet lowered the levels of pro-inflammatory cytokines TNF-α and IL-1ß in the plasma. Further analyses showed that the LC diet downregulated genes (specifically TLR4 and MyD88) linked to the TLRs/MyD88/NF-κB signaling pathway in the small intestine. Additionally, 16SrDNA sequencing data revealed that LC supplementation increased the α diversity of intestinal microorganisms and the relative abundance of Lactobacillus. In summary, the LC-supplemented diet effectively mitigated the adverse effects of E. coli K88, including intestinal barrier damage and inflammation. Furthermore, it improved the structure of the intestinal flora, ultimately contributing to better growth performance in piglets.

Maternal supplementation with Artemisia annua L. ameliorates intestinal inflammation via inhibiting the TLR4/NF-κB and MAPK pathways and improves the oxidative stability of offspring.

Artemisia annua L. (A. annua) contains artemisinin, which attracts attention on account of its anti-inflammatory and anti-oxidant effects. Increased intestinal inflammation, oxidative stress, and hypoimmunity commonly occur in neonatal and early-weaning piglets. Abundant evidence suggests that maternal nutritional interventions during pregnancy modify the offspring's long-term gut development. The present study was conducted to investigate the effects of maternal A. annua extract (AAE) supplementation on the offspring's intestinal inflammation and redox status. A total of 90 pregnant sows were assigned randomly and equally into the control (CON) group (fed with a basal diet) and the 0.1% (AAE) group (basal diet with 1.0 g kg-1 AAE) during late gestation and lactation. The results showed that 0.1% AAE supplementation significantly decreased the contents and relative mRNA expressions of interleukin (IL)-1ß, IL-6, and IL-12, and tumor necrosis factor-α in the small intestine of the newborn and weaned piglets (offspring) (P < 0.05). There were higher activities of total antioxidant capacity and total superoxide dismutase, whereas a lower concentration of malondialdehyde in the small instestine of offspring in the 0.1% AAE group than that in the CON group (P < 0.05). Furthermore, the 0.1% AAE group decreased the mRNA and protein expressions of Toll-like receptor 4 (TLR4) and inhibited the activation of TLR4-mediated nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways (P < 0.05). The mRNA expression of peroxisome proliferator activated receptor γ (PPARγ), porcine beta-defensin (PBD)-1, PBD-2, PBD-3, mucin (MUC)-1, MUC-2 and MUC-4 was significantly enhanced in the small intestine of both neonatal and weanling piglets (P < 0.05). Together, these results showed that maternal 0.1% AAE supplementation improved the redox status and attenuated the neonatal and early-weaning associated inflammatory response in the offspring's small intestine, possibly by suppressing the activation of the TLR4/NF-κB and MAPK inflammatory pathways, and stimulated expressions of beta-defensins, mucins, and PPARγ to promote inflammation resolution and innate immunity response.

Glyceryl butyrate attenuates enterotoxigenic Escherichia coli-induced intestinal inflammation in piglets by inhibiting the NF-κB/MAPK pathways and modulating the gut microbiota.

The aims of this study were to evaluate whether a diet supplemented with glyceryl butyrate could attenuate the immune-inflammatory response in piglets challenged with enterotoxigenic Escherichia coli (ETEC), and to explore the mechanisms of its regulation. Eighteen weaning piglets were assigned to three diets: basal diet (CON), antibiotics diet (ATB), and 0.5% glyceryl butyrate diet (GB group). Significantly lower concentrations of IL-1ß, IL-6 and TNF-α in the jejunum and IL-6 in the ileum were observed in the GB group than that in the CON group (P < 0.05). Moreover, a decreasing trend of IL-1ß (P = 0.075) and TNF-α (P = 0.070) was observed in the ileum in the GB group. Correspondingly, the GB group had significantly increased mRNA expression of porcine beta defensins (pBDs) in the jejunum (pBD1, pBD2, pBD114 and pBD129) and ileum (pBD2, pBD3, pBD114 and pBD129) (P < 0.05), and protein abundance of Claudin 1, Occludin, and ZO-1 in the jejunum and ileum (P < 0.05). Further research results showed that the improvement of beta defensins and tight junctions in the GB group was related to the decreased phosphorylation of the NFκB/MAPK pathway. In addition, the results of 16S rDNA sequencing showed that glycerol butyrate supplementation altered the ileal microbiota composition of piglets, increasing the relative abundance of Lactobacillus reuteri, Lactobacillus salivarius, and Lactobacillus agrilis. In summary, glyceryl butyrate attenuated the immune-inflammatory response in piglets challenged with ETEC by inhibiting the NF-κB/MAPK pathways and modulating the gut microbiota, and thus improved piglet intestinal health.

Dietary Supplementation of Enzymatically Treated Artemisia annua L. Improves Lactation Performance, Alleviates Inflammatory Response of Sows Reared Under Heat Stress, and Promotes Gut Development in Preweaning Offspring.

Artemisia annua L., which is known for its antimalarial compound artemisinin, has commonly been used for its anti-inflammatory and antibacterial functions. Enzymatically treating Artemisia annua L. can improve its bioavailability. The purpose of this study was to investigate the effects of dietary enzymatically treated Artemisia annua L. (EA) supplementation in late gestation and lactation diets on sow performance, serum hormone, inflammatory cytokines, and immunoglobulin level of heat-stressed sows. A total of 135 multiparous sows (Large White × Landrace) on day 85 of gestation were selected and randomly distributed into 3 groups with 45 replicates per group. The control group was reared under standard conditions (temperature: 27.12 ± 0.18°C, THI (temperature-humidity index): 70.90 ± 0.80) and fed with basal diet. The heat stress (HS) and HS + EA groups were raised in heat-stressed conditions (temperature: 30.11 ± 0.16°C, THI: 72.70 ± 0.60) and fed with basal diets supplemented with 0 or 1.0 g/kg EA, respectively. This trial lasted for 50 consecutive days until day 21 of lactation. Compared with the control group, HS increased the concentrations of serum endotoxin and heat shock protein 70 (HSP-70), and inflammatory cytokines in serum, colostrum, and 14 day milk of sows. Meanwhile, the EA supplementation decreased levels of serum endotoxin, HSP-70, and inflammatory cytokines in both sows and offspring and increased serum triiodothyronine (T3) level and average daily feed intake (ADFI) of sows. In addition, EA significantly improved average daily gain (ADG) and altered intestinal morphology with an increased villus height in the duodenum and ileum of piglets. Collectively, EA supplementation at 1.0 g/kg in late gestation and lactation diets alleviated the adverse effects of HS, which were reflected by enhancing ADFI and decreasing endotoxin as well as inflammatory cytokine levels in the serum and colostrum of heat-stressed sows, while promoting ADG and gut development of their offspring.

Artemisinin Protects Porcine Mammary Epithelial Cells against Lipopolysaccharide-Induced Inflammatory Injury by Regulating the NF-κB and MAPK Signaling Pathways.

Artemisinin performs a variety of biological functions, such as anti-cancer, anti-inflammatory, anti-viral, and anti-oxidant effects. However, the effects of artemisinin on sow mastitis have not been studied. The results of the current study showed that mRNA expression abundance and content of the inflammatory factors interleukin-1ß (IL-1ß), tumor necrosis factor α (TNF-α), and interleukin-6 (IL-6) were significantly increased when using 50 µg/mL LPS to stimulate pMECs for 24 h (p < 0.05). Pretreatment with 20 µM artemisinin weakened LPS-induced inflammatory damage in pMECs and decreased mRNA expression abundance and the content of inflammatory factors (IL-1ß, IL-6, and TNF-α) in pMECs (p < 0.05). Mechanistically, artemisinin inhibited LPS-induced activation of the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. In summary, the pretreatment of pMECs with artemisinin showed enhanced anti-inflammatory activity against LPS-induced inflammation.