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Nutritional regulation of endogenous antimicrobial peptide (AMP) expression is considered a promising nonantibiotic approach to suppressing intestinal infection of pathogen. The current study investigated the effects of l-arginine on LPS-induced intestinal inflammation and barrier dysfunction in vivo and in vitro. The results revealed that l-arginine attenuated LPS-induced inflammatory response, inhibited the downregulation of tight junction proteins (TJP) ( p < 0.05) by LPS, and maintained intestinal integrity. In porcine intestinal epithelial cells (IPEC-J2), l-arginine obviously suppressed ( p < 0.05) the levels of IL-6 (220.63 ± 2.82), IL-8 (333.95 ± 3.75), IL-1β (693.08 ± 2.38), and TNF-α (258.04 ± 4.14) induced by LPS. Furthermore, l-arginine diminished the LPS-induced expression of Toll-like receptor 4 (TLR4) and inhibited activation of TLR4-mediated nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Importantly, we proposed a new mechanism that l-arginine had the ability to stimulate the expression of porcine epithelial β-defensins through activating the mammalian target of the rapamycin (mTOR) pathway, which exerts anti-inflammatory influence. Moreover, pBD-1 gene overexpression decreased ( p < 0.05) the TNF-α level stimulated by LPS in IPEC-J2 cells (4.22 ± 1.64). The present study indicated that l-arginine enhanced disease resistance through inhibiting the TLR4/NF-κB and MAPK pathways and partially, possibly through increasing the intestinal β-defensin expression.

Salmonella typhimurium is one of the main causes of intestinal diseases, affecting the health of humans and livestock. Ethyl pyruvate (EP), which is ordinarily an edible spice, has been indicated to exert anti-inflammatory effects and preserve intestinal barrier function. In this study, intestinal immune function and signaling pathways activated by EP were investigated in vivo in S. typhimurium-challenged BALB/c mice and in vitro in RAW264.7 cells. EP improved body weight loss and the organ index of the liver and spleen (p < 0.05). Serum IgA and IgM levels were significantly increased in EP-treated mice (p < 0.05). According to histopathological and immunohistochemical staining, EP significantly increased the villus height, reduced edema in the jejunum and increased the levels of claudin-1, occludin-1 and ZO-1 proteins compared to the Salmonella-treated group (p < 0.05). In addition, EP decreased the levels of the IL-6, IL-1β and TNF-α mRNA levels in jejunum, liver, spleen and RAW264.7 cells (p < 0.05). EP decreased the levels of TLR4, phosphorylated p38MAPK and ERK1/2 in mice infected with S. typhimurium (p < 0.05). In conclusion, EP effectively protected BALB/c mice from an intestinal S. typhimurium infection by improving the activity of the humoral immune system, reducing intestinal barrier damage, and inhibiting proinflammatory cytokine production in the jejunum by modulating the TLR4/MAPK signaling pathway. Based on these findings, EP has the potential to inhibit inflammation or to serve as an immune-enhancing adjuvant., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Infection with pathogenic bacteria during nonantibiotic breeding is one of the main causes of animal intestinal diseases. Oleanolic acid (OA) is a pentacyclic triterpene that is ubiquitous in plants. Our previous work demonstrated the protective effect of OA on intestinal health, but the underlying molecular mechanisms remain unclear. This study investigated whether dietary supplementation with OA can prevent diarrhea and intestinal immune dysregulation caused by enterotoxigenic Escherichia coli (ETEC) in piglets. The key molecular role of bile acid receptor signaling in this process has also been explored. Results: Our results demonstrated that OA supplementation alleviated the disturbance of bile acid metabolism in ETEC-infected piglets (P < 0.05). OA supplementation stabilized the composition of the bile acid pool in piglets by regulating the enterohepatic circulation of bile acids and significantly increased the contents of UDCA and CDCA in the ileum and cecum (P < 0.05). This may also explain why OA can maintain the stability of the intestinal microbiota structure in ETEC-challenged piglets. In addition, as a natural ligand of bile acid receptors, OA can reduce the severity of intestinal inflammation and enhance the strength of intestinal epithelial cell antimicrobial programs through the bile acid receptors TGR5 and FXR (P < 0.05). Specifically, OA inhibited NF-κB-mediated intestinal inflammation by directly activating TGR5 and its downstream cAMP-PKA-CREB signaling pathway (P < 0.05). Furthermore, OA enhanced CDCA-mediated MEK-ERK signaling in intestinal epithelial cells by upregulating the expression of FXR (P < 0.05), thereby upregulating the expression of endogenous defense molecules in intestinal epithelial cells. Conclusions: In conclusion, our findings suggest that OA-mediated regulation of bile acid metabolism plays an important role in the innate immune response, which provides a new diet-based intervention for intestinal diseases caused by pathogenic bacterial infections in piglets. [ABSTRACT FROM AUTHOR]

BACKGROUND: Oleanolic acid (OA) is a pentacyclic triterpenoid compound that is present at high levels in olive oil and has several promising pharmacological effects, such as liver protection and anti‐inflammatory, antioxidant, and anticancer effects. The purpose of the present study was to assess whether OA treatment affects gut health compared to a control condition, including gut microbiota and intestinal epithelial immunity. RESULTS: Illumina MiSeq sequencing (16S rRNA gene) was used to investigate the effect of OA on the microbial community of the intestinal tract, while Illumina HiSeq (RNA‐seq) technology was used to investigate the regulatory effect of OA on gene expression in intestinal epithelial cells, which allowed for a comprehensive analysis of the effects of OA on intestinal health. The results showed that the consumption of OA initially controlled weight gain in mice and altered the composition of the gut microbiota. At the phylum level, OA significantly increased the relative abundances of cecum Firmicutes but decreased the abundance of Actinobacteria, and at the genus level it increased the relative abundance of potentially beneficial bacteria such as Oscillibacter and Ruminiclostridium 9. Oleanolic acid treatment also altered the expression of 12 genes involved in the Kyoto Encyclopedia of Genes and Genomes（KEGG）pathways of complement and coagulation cascades, hematopoietic cell lineage, and leukocyte transendothelial migration in intestinal epithelial cells to improve gut immunity. CONCLUSION: Intake of OA can contribute beneficial effects by optimizing gut microbiota and altering the immune function of intestinal epithelial cells, potentially to improve intestinal health status. © 2021 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Aquaporins (AQP) are a class of water channel membrane proteins that are widely expressed in the gut. The biological functions of aquaporins, which regulate the absorption and secretion of water molecules and small solutes, maintain the stable state of the intestine, regulate cell proliferation and migration, participate in the process of intestinal inflammation, and mediate tumorigenesis, demonstrate the physiological significance of these channels in intestinal health. The pathology of many intestinal diseases is associated with changes in the location and expression of aquaporins, such as intestinal infection, which can change the expression and distribution of AQPs in intestinal tissues/cells by affecting cytokines and chemokines. This can lead to various intestinal diseases such as diarrhoea, which also suggests the importance of aquaporins in the prevention and treatment of intestinal diseases. This review summarizes the relationship between aquaporins and intestinal physiology and diseases and focuses on drugs (such as plant extracts) or diets that can regulate intestinal health by regulating aquaporins. It provides a basis for establishing aquaporins as biomarkers and therapeutic targets for intestinal health. [ABSTRACT FROM AUTHOR]