Kaempferol, a secondary metabolite found in plants, is a naturally occurring flavonoid displaying significant potential in various biological activities. The chemical structure of kaempferol is distinguished by the presence of phenyl rings and four hydroxyl substituents, which make it an exceptional radical scavenger. Most recently, an increasing number of studies have demonstrated the significance of kaempferol in the regulation of intestinal function and the mitigation of intestinal inflammation. The focus of the review will primarily be on its impact in terms of antioxidant properties, inflammation, maintenance of intestinal barrier function, and its potential in the treatment of colorectal cancer and obesity. Future research endeavors should additionally give priority to investigating the specific dosage and duration of kaempferol administration for different pathological conditions, while simultaneously conducting deeper investigations into the comprehensible mechanisms of action related to the regulation of aryl hydrocarbon receptor (AhR). This review intends to present novel evidence supporting the utilization of kaempferol in the regulation of gut health and the management of associated diseases.

The contamination of deoxynivalenol (DON) in feed is a global problem, which seriously threatens the productivity efficiency and welfare of farm animals and the food security of humans. Pig is the most sensitive species to DON, and is readily exposed to DON through its grain-enriched diet. The intestine serves as the first biological barrier to ingested mycotoxin, and is, therefore, the first target of DON. In the past decade, a growing amount of attention has been paid to plant-derived polyphenols as functional compounds against DON-induced oxidative stress and intestinal toxicity in pigs. In this review, we systematically updated the latest research progress in plant polyphenols detoxifying DON-induced intestinal toxicity in swine. We also discussed the potential underlying mechanism of action of polyphenols as Nrf2 activators in protecting against DON-induced enterotoxicity of swine. The output of this update points out an emerging research direction, as polyphenols have great potential to be developed as feed additives for swine to counteract DON-induced oxidative stress and intestinal toxicity.

At a global level, the supply of protein sources is insufficient to support the current magnitude of pig production. Moreover, given the exorbitant expense of conventional protein feed options like soybean meal and fish meal, it becomes imperative to promptly explore alternative sources of protein feed for the sustainable advancement of the pig industry. Cottonseed meal, a by-product from the extraction of cottonseed oil, exhibits significant potential as a protein source for pig feed owing to its high protein content, high yield, low cost, well-balanced amino acid composition, and sufficient accessibility. However, cottonseed meal possesses several anti-nutritional factors, especially gossypol, which adversely affect growth and reproductive performance, resulting in the limited utilization of cottonseed meal in pig feed. To maximize the benefits of cottonseed meal and promote its application in pig production, it is imperative to acquire comprehensive knowledge regarding its nutritional value and current utilization. In this review, we initially presented a summary of the nutritional values of cottonseed meal, primary anti-nutritional factors, and effective approaches for improving its utilization as a protein source feed. Subsequently, we comprehensively summarized the latest research progress of cottonseed meal application in pig nutrition over the past decade. The outcome of this review serves as a theoretical foundation and practical guidance for the research and application of cottonseed meal in pig nutrition and promotes the reduction of soybean meal utilization in the pig industry.

Skeletal muscle-fat interaction is essential for maintaining organismal energy homeostasis and managing obesity by secreting cytokines and exosomes, but the role of the latter as a new mediator in inter-tissue communication remains unclear. Recently, we discovered that miR-146a-5p was mainly enriched in skeletal muscle-derived exosomes (SKM-Exos), 50-fold higher than in fat exosomes. Here, we investigated the role of skeletal muscle-derived exosomes regulating lipid metabolism in adipose tissue by delivering miR-146a-5p. The results showed that skeletal muscle cell-derived exosomes significantly inhibited the differentiation of preadipocytes and their adipogenesis. When the skeletal muscle-derived exosomes co-treated adipocytes with miR-146a-5p inhibitor, this inhibition was reversed. Additionally, skeletal muscle-specific knockout miR-146a-5p (mKO) mice significantly increased body weight gain and decreased oxidative metabolism. On the other hand, the internalization of this miRNA into the mKO mice by injecting skeletal muscle-derived exosomes from the Flox mice (Flox-Exos) resulted in significant phenotypic reversion, including down-regulation of genes and proteins involved in adipogenesis. Mechanistically, miR-146a-5p has also been demonstrated to function as a negative regulator of peroxisome proliferator-activated receptor γ (PPARγ) signaling by directly targeting growth and differentiation factor 5 (GDF5) gene to mediate adipogenesis and fatty acid absorption. Taken together, these data provide new insights into the role of miR-146a-5p as a novel myokine involved in the regulation of adipogenesis and obesity via mediating the skeletal muscle-fat signaling axis, which may serve as a target for the development of therapies against metabolic diseases, such as obesity.

Secretory immunoglobulin A (SIgA) plays an important role in gut acquired immunity and mucosal homeostasis. Breast milk is the irreplaceable nutritional source for mammals after birth. Current studies have shown the potential functional role of milk-derived small extracellular vesicles (sEVs) and their RNAs cargo in intestinal health and immune regulation. However, there is a lack of studies to demonstrate how milk-derived sEVs affect intestinal immunity in recipient. In this study, through in vivo experiments, we found that porcine milk small extracellular vesicles (PM-sEVs) promoted intestinal SIgA levels, and increased the expression levels of polymeric immunoglobulin receptor (pIgR) both in mice and piglet. We examined the mechanism of how PM-sEVs increased the expression level of pIgR in vitro by using a porcine small intestine epithelial cell line (IPEC-J2). Through bioinformatics analysis, dual-luciferase reporter assays, and overexpression or knockdown of the corresponding non-coding RNAs, we identified circ-XPO4 in PM-sEVs as a crucial circRNA, which leads to the expression of pIgR via the suppression of miR-221-5p in intestinal cells. Importantly, we also observed that oral administration of PM-sEVs increased the level of circ-XPO4 and decreased the level of miR-221-5p in small intestine of piglets, indicating that circRNAs in milk-derived sEVs act as sponge for miRNAs in recipients. This study, for the first time, reveals that PM-sEVs have a capacity to stimulate intestinal SIgA production by delivering circRNAs to receptors and sponging the recipient’s original miRNAs, and also provides valuable data for insight into the role and mechanism of animal milk sEVs in intestinal immunity.