Introduction: The gastrointestinal tract is integral to defending against external contaminants, featuring a complex array of immunological, physical, chemical, and microbial barriers. Mycotoxins, which are toxic metabolites from fungi, are pervasive in both animal feed and human food, presenting substantial health risks.Methods: This review examines the pharmacological, toxicological, and microbiological impacts of natural products on mycotoxicosis, with a particular focus on the gut-x axis. The analysis synthesizes current understanding and explores the role of natural products rich in polysaccharides, polyphenols, flavonoids, and saponins. Results: The review highlights that mycotoxins can disrupt intestinal integrity, alter inflammatory responses, damage the mucus layer, and disturb the bacterial balance. The toxins' effects are extensive, potentially harming the immune system, liver, kidneys, and skin, and are associated with serious conditions such as cancer, hormonal changes, genetic mutations, bleeding, birth defects, and neurological issues. Natural products have shown potential anticancer, anti-tumor, antioxidant, immunomodulatory, and antitoxic properties.Discussion: The review underscores the emerging therapeutic strategy of targeting gut microbial modulation. It identifies knowledge gaps and suggests future research directions to deepen our understanding of natural products' role in gut-x axis health and to mitigate the global health impact of mycotoxin-induced diseases.

Moringa oleifera (M. oleifera) is a plant with significant medicinal and nutritional value and contains various bioactive compounds, particularly in its leaves (MOL). This study sought to explore the impact of M. oleifera leaf polysaccharides (MOLPs) on lipopolysaccharide (LPS)-activated intestinal epithelial cells (IEC6) and to uncover the mechanisms involved. The cytotoxicity of MOLP on IEC6 cells was assessed using the Cell Counting Kit-8 (CCK-8) assay, which demonstrated a safe concentration range of 0–1280 µg/mL. The impact of MOLP on cell viability was further evaluated over 12 to 48 h. IEC6 cells were treated with three concentrations of MOLP low (25 µg/mL), medium (50 µg/mL), and high (100 µg/mL) alongside LPS (50 µg/mL) stimulation for one day. The findings revealed that treatment with MOLP significantly promoted cell migration and increased the production of interleukin-10 (IL-10), while it simultaneously decreased cell apoptosis and the levels of pro-inflammatory cytokines, such as tumour necrosis factor alpha (TNF-α), interleukin 1β (IL-1β), and interleukin 6 (IL-6). Additionally, MOLP treatments across all concentrations significantly reduced the expression of Toll-like receptor 4 (TLR-4), myeloid differentiation primary response 88 (MyD88), phosphorylated nuclear factor kappa B-alpha (pIκB-α), and phosphorylated NF-κB p65 signalling pathways. Moreover, MOLP restored the expression of tight junction proteins, such as zonula occludens-1 (ZO-1) and occludin, which had been disrupted by LPS. These results indicate that MOLP exhibits anti-inflammatory properties by inhibiting inflammatory signalling pathways and maintaining intestinal barrier integrity through the upregulation of tight junction proteins in IEC6 cells. This study enhances our understanding of the anti-inflammatory capabilities of MOLP.

Nuclear receptors are involved in multiple biological processes, among which RORγ can regulate the expression of inflammation-related genes and is thus frequently used as a therapeutic target for cancer. Canine mammary cancer is one of the most common tumor diseases in dogs, with a relative incidence rate of 46.71% for CMT in China over the past five years, severely threatening the life and health of dogs. Therefore, the search for novel drugs targeting canine mammary cancer is of great significance. This study aims to investigate how the RORγ inhibitors W6134 and XY018 affect the expression of inflammatory genes through histone modifications in CMT-N7 cells. These results show that W6134 and XY018 can upregulate signaling pathways related to inflammation and apoptosis and influence the expression of associated genes. The close link between RORγ and inflammation-related genes further confirms that RORγ may serve as a therapeutic target for canine cancer. Additionally, ChIP-qPCR was used to detect the enrichment of histone markers such as P300, H3K27ac, H3K4me1, H3K9la, and H3K9bhb at the target loci of CXCL10 and MECOM genes. Collectively, our findings provide molecular evidence for the protective role of RORγ in canine mammary cancer, potentially by regulating inflammatory pathways via histone modifications, offering new insights for improving the cure rate and survival of affected dogs.