Selenium maintains intestinal epithelial cells to activate M2 macrophages against deoxynivalenol injury.

Selenium (Se) is indispensable in alleviating various types of intestinal injuries. Here, we thoroughly investigated the protective effect of Se on the regulation of the epithelial cell-M2 macrophages pathway in deoxynivalenol (DON)-induced intestinal damage. In the present study, Se has positive impacts on gut health by improving gut barrier function and reducing the levels of serum DON in vivo. Furthermore, our study revealed that Se supplementation increased the abundances of GPX4, p-PI3K, and AKT, decreased the levels of 4-HNE and inhibited ferroptosis. Moreover, when mice were treated with DON and Fer-1(ferroptosis inhibitor), ferroptosis was suppressed and PI3K/AKT pathway was activated. These results indicated that GPX4-PI3K/AKT-ferroptosis was a predominant pathway in DON-induced intestinal inflammation. Interestingly, we discovered that both the number of M2 anti-inflammatory macrophages and the levels of CSF-1 decreased while the pro-inflammatory cytokine IL-6 increased in the intestine and MODE-K cells supernatant. Therefore, Se supplementation activated the CSF-1-M2 macrophages axis, resulting in a decrease in IL-6 expression and an enhancement of the intestinal anti-inflammatory capacity. This study provides novel insights into how intestinal epithelial cells regulate the CSF-1-M2 macrophage pathway, which is essential in maintaining intestinal homeostasis confer to environmental hazardous stimuli.

Targeting deoxynivalenol for degradation by a chimeric manganese peroxidase/glutathione system.

The manganese peroxidase (MnP) can degrade multiple mycotoxins including deoxynivalenol (DON) efficiently; however, the lignin components abundant in foods and feeds were discovered to interfere with DON catalysis. Herein, using MnP from Ceriporiopsis subvermispora (CsMnP) as a model, it was demonstrated that desired catalysis of DON, but not futile reactions with lignin, in the reaction systems containing feeds could be achieved by engineering MnP and supplementing with a boosting reactant. Specifically, two successive strategies (including the fusion of CsMnP to a DON-recognizing ScFv and identification of glutathione as a specific targeting enhancer) were combined to overcome the lignin competition, which together resulted into elevation of the degradation rate from 2.5% to as high as 82.7% in the feeds. The method to construct a targeting MnP and fortify it with an additional enhancer could be similarly applied to catalyze the many other mycotoxins with yet unknown responsive biocatalysts.

Effects of a Bentonite Clay Product and a Preservative Blend on Ileal and Fecal Nutrient Digestibility in Pigs Fed Wheat Naturally Contaminated with Deoxynivalenol.

The objectives were to determine the effects of dietary deoxynivalenol (DON) on apparent ileal digestibility (AID) of nutrients and to evaluate the efficacy of a bentonite (BEN) and a preservative blend (PB) product for alleviating DON effects on the nutrient digestibility of pigs. Twelve crossbred barrows with an initial body weight of 69.4 kg (standard deviation = 3.5) equipped with a T-cannula in the distal ileum were allotted a triplicated 4 × 2 incomplete Latin square design with four dietary treatments and two periods. Dietary treatments were (1) an uncontaminated diet, (2) a contaminated diet (CD) mainly based on contaminated wheat with 1.6 mg/kg DON, (3) CD + 0.25% PB consisting of preservation components as major sources, antioxidants, microorganisms, and amino acids (AA), and (4) CD + 0.25% BEN. The AID and ATTD of dry matter, organic matter, crude protein, most minerals, and most AA were not affected by DON contamination. Dietary DON decreased the AID and ATTD of sodium (p < 0.05) but were restored by supplementing the PB product (p < 0.05). The AID of zinc was increased (p < 0.05) by dietary DON, but supplementing BEN decreased zinc digestibility (p < 0.05). The AID of Arg, Ile, Thr, and Asp was decreased (p < 0.05) by BEN addition. In conclusion, dietary DON affected the digestibility of some minerals but not AA in pigs. Supplemental BEN can negatively affect the nutrient digestibility of some minerals and AA in pigs. The addition of a PB product in pig diets can restore digestibility of sodium but not of other nutrients. Based on these observations, feed additives for alleviating DON effects on nutrient digestibility of pigs can be carefully selected by swine diet formulators.

Retinoic Acid-PPARα Mediates ß-Carotene Resistance to Placental Dysfunction Induced by Deoxynivalenol.

Deoxynivalenol (DON), one of the most polluted mycotoxins in the environment and food, has been proven to have strong embryonic and reproductive toxicities. However, the effects of DON on placental impairment and effective interventions are still unclear. This study investigated the effect of ß-carotene on placental functional impairment and its underlying molecular mechanism under DON exposure. Adverse pregnancy outcomes were caused by intraperitoneal injection of DON from 13.5 to 15.5 days of gestation in mice, resulting in higher enrichment of DON in placenta than in other tissue samples. Interestingly, 0.1% ß-carotene dietary supplementation could significantly alleviate DON-induced pregnancy outcomes. Additionally, in vivo and in vitro placental barrier models demonstrated the association of DON-induced placental function impairment with placental permeability barrier disruption, angiogenesis impairment, and oxidative stress induction. Moreover, ß-carotene regulated DON-induced placental toxicity by activating the expressions of claudin 1, zonula occludens-1, and vascular endothelial growth factor-A through retinoic acid-peroxisome proliferator-activated receptor α signaling.

Effective protective agents against organ toxicity of deoxynivalenol and their detoxification mechanisms: A review.

Deoxynivalenol (DON) is one of the most prevalent mycotoxins in feed, which causes organ toxicity in animals. Therefore, reducing DON-induced organ toxicity can now be accomplished effectively using protective agents. This review provides an overview of multiple studies on a wide range of protective agents and their molecular mechanisms against DON organ toxicity. Protective agents include plant extracts, yeast products, bacteria, peptides, enzymes, H2, oligosaccharides, amino acids, adsorbents, vitamins and selenium. Among these, biological detoxification of DON using microorganisms to reduce the toxicity of DON without affecting the growth performance of pigs may be the most promising detoxification strategy. This paper also evaluates future developments related to DON detoxification and discusses the detoxification role and application potential of protective agents. This paper provides new perspectives for future research and development of safe and effective feed additives.

Effects of Mycotoxin-Sequestering Agents on Growth Performance and Nutrient Utilization of Growing Pigs Fed Deoxynivalenol-Contaminated Diets.

The objective of this study was to investigate the effects of supplemental mycotoxin-sequestering agents on growth performance and nutrient utilization in growing pigs fed deoxynivalenol (DON)-contaminated diets. Twelve barrows with an initial body weight of 35.5 kg (standard deviation = 1.3) were assigned to six dietary treatments in a replicated 6 × 5 incomplete Latin square design. Five experimental diets consisted of an uncontaminated diet (PC), a DON-contaminated diet at 6.89 mg/kg (NC), NC + bentonite 0.5%, NC + yeast cell wall 0.5%, and NC + a mixture product 0.5% which consisted of enzymes, microorganisms, minerals, and plant extracts. Pigs had ad libitum access to the five diets. In the last group, the PC diet was restrictedly provided to pigs at the quantity of feed consumption of the NC group. Average daily gain, average daily feed intake, and gain:feed were not affected by supplemental mycotoxin-sequestering agents except for the mixed product that tended to improve (p = 0.064) gain:feed in pigs fed DON-contaminated diets. The apparent total tract digestibility (ATTD) of dry matter was not affected by DON contamination or by supplemental mycotoxin-sequestering agents, whereas the ATTD of Ca was decreased (p = 0.032) by supplemental yeast cell wall in pigs fed DON-contaminated diets. The ATTD of P was greater (p = 0.042) in pigs fed the NC diet compared with the pigs fed the restricted amount of the PC diet. In conclusion, bentonite and yeast cell wall did not affect growth performance of pigs fed DON-contaminated diets, but a supplemental mixed product consisting of enzymes, microorganisms, minerals, and plant extracts partially alleviated the negative effects of dietary DON on the gain:feed of pigs. Calcium digestibility was decreased by supplemental yeast cell wall in pigs fed DON-contaminated diets. Based on the present work, the use of a mixed product consisting of enzymes, microorganisms, minerals, and plant extracts is suggested, and the reduction of Ca digestibility by yeast cell wall needs to be considered in diet formulations.

Ameliorative Effects of Luteolin and Activated Charcoal on Growth Performance, Immunity Function, and Antioxidant Capacity in Broiler Chickens Exposed to Deoxynivalenol.

Deoxynivalenol (DON, Vomitoxin) is a threatening mycotoxin that mainly produces oxidative stress and leads to hepatotoxicity in poultry. Antioxidant dietary supplements dramatically boost immunity, safeguarding animals from DON poisoning. Luteolin (LUT) is an active plant-derived compound that poses influential antioxidants. This study explored the effectiveness of LUT in combination with activated charcoal (AC) in detoxifying DON in broilers. The 180 one-day broiler chickens were allocated into five different groups having six replicates in each group, provided with ad libitum feed during the trial period (28 days) as follows: in the control group, basal diet (feed with no supplementation of LUT, AC or DON); in group 2, a basal diet added with 10 mg/kg DON from contaminated culture (DON); in group 3, a basal diet augmented by 350 mg/kg LUT and DON 10 mg/kg (DON + LUT); in group 4, a basal diet supplemented by DON 10 mg/kg + AC 200 mg/kg (DON + AC); and in group 5, a basal diet supplemented by 10 mg/kg DON + 350 mg/kg LUT + 200 mg/kg AC (DON + LUT + AC). Concerning the control group, the DON-treated broilers demonstrated a significant decrease in growth performance (p < 0.05) and serum immunoglobulin (p < 0.05) contents, negatively changing the serum biochemical contents and enzymatic activities and an increase in histopathological liver lesions. Furthermore, DON substantially increased (p < 0.05) malondialdehyde (MDA) concentration and decreased total superoxide dismutase (T-SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) levels in the serum and liver. The intake of AC and LUT to the DON-contaminated diet decreased DON residue in the liver and potentially reduced the adverse effects of DON. Considering the results, supplementation of LUT with mycotoxin adsorbent has protective effects against mycotoxicosis caused by DON. It could be helpful for the development of novel treatments to combat liver diseases in poultry birds. Our findings may provide important information for applying LUT and AC in poultry production.

Superoxide dismutase ameliorates oxidative stress and regulates liver transcriptomics to provide therapeutic benefits in hepatic inflammation.

Background: Oxidative stress refers to the imbalance between oxidants and antioxidants in organisms and often induces hepatic inflammation. Supplementing exogenous superoxide dismutase is an effective way to alleviate oxidative stress; however, the effects and mechanisms by which superoxide dismutase alleviates hepatic inflammation remain unclear. Methods: This study established a Kunming mouse model to verify and investigate the oxidative stress and hepatic inflammation-alleviating effects of the superoxide dismutase oral supplement that was prepared by our research group in a previous study. Results: The superoxide dismutase product significantly restored the body weight and liver alanine transaminase, aspartate aminotransferase, superoxide dismutase, catalase, glutathione, and glutathione peroxidase levels of oxidative stress induced mice. Moreover, exogenous superoxide dismutase significantly inhibited interleukin 1ß and interleukin 6 mRNA expression in the livers of mice with hepatic inflammation. Transcriptomic analysis indicated that superoxide dismutase had a significant inhibitory effect on Endog expression, alleviating oxidative stress damage, and mediating liver cell apoptosis by regulating the expression of Rab5if, Hnrnpab, and Ifit1. Conclusion: Our research verified the oxidative stress remediation effects of superoxide dismutase and its therapeutic role against hepatic inflammation. This study can lay a foundation for investigating the mechanism by which superoxide dismutase alleviates hepatic disease.

Global distribution, toxicity to humans and animals, biodegradation, and nutritional mitigation of deoxynivalenol: A review.

Deoxynivalenol (DON) is one of the main types of B trichothecenes, and it causes health-related issues in humans and animals and imposes considerable challenges to food and feed safety globally each year. This review investigates the global hazards of DON, describes the occurrence of DON in food and feed in different countries, and systematically uncovers the mechanisms of the various toxic effects of DON. For DON pollution, many treatments have been reported on the degradation of DON, and each of the treatments has different degradation efficacies and degrades DON by a distinct mechanism. These treatments include physical, chemical, and biological methods and mitigation strategies. Biodegradation methods include microorganisms, enzymes, and biological antifungal agents, which are of great research significance in food processing because of their high efficiency, low environmental hazards, and drug resistance. And we also reviewed the mechanisms of biodegradation methods of DON, the adsorption and antagonism effects of microorganisms, and the different chemical transformation mechanisms of enzymes. Moreover, nutritional mitigation including common nutrients (amino acids, fatty acids, vitamins, and microelements) and plant extracts was discussed in this review, and the mitigation mechanism of DON toxicity was elaborated from the biochemical point of view. These findings help explore various approaches to achieve the best efficiency and applicability, overcome DON pollution worldwide, ensure the sustainability and safety of food processing, and explore potential therapeutic options with the ability to reduce the deleterious effects of DON in humans and animals.

Selenium nanoparticles alleviate deoxynivalenol-induced intestinal epithelial barrier dysfunction by regulating endoplasmic reticulum stress in IPEC-J2 cells.

The intestinal epithelial barrier plays a crucial role in maintaining human and animal health. Deoxynivalenol (DON) is a mycotoxin that contaminates cereal-based foods worldwide, which is a serious threat to human and animal health. This study was aimed to investigate the protective effect of selenium nanoparticles (SeNPs) synthesized by Lactobacillus casei ATCC 393 against DON-induced intestinal epithelial barrier dysfunction and its relationship with PERK-mediated signaling pathway. IPEC-J2 cells were randomly assigned to four groups: Con (vehicle), DON (0.6 µg DON/mL, 48 h), SeNPs+DON (8 µg Se/mL, 24 h; 0.6 µg DON/mL, 48 h) and SeNPs (8 µg Se/mL, 24 h). Compared with Con group, the transepithelial electrical resistance (TEER) and the tight junction proteins expression of IPEC-J2 cells exposed to DON was increased and decreased, respectively. In addition, DON exposure led to increased ROS content, decreased antioxidant capacity, structural damage of endoplasmic reticulum (ER), and activation of endoplasmic reticulum stress (ERS)-related protein kinase R-like endoplasmic reticulum kinase (PERK) pathway in IPEC-J2. Compared with SeNPs+DON group, SeNPs alleviated oxidative stress, ER structure damage and PERK pathway activation and the increase of intestinal epithelial permeability of IPEC-J2 cells exposed to DON. PERK agonist (CCT020312) and inhibitor (GSK2656157) treatments were performed to identify the role of PERK signaling pathway in the regulatory effects of SeNPs on DON-induced intestinal epithelial barrier dysfunction. Compared with SeNPs+DON group, PERK agonist increased the expression levels of p-PERK. PERK inhibitor exerted a similar inhibitory effect to SeNPs on the p-PERK expression. In conclusion, SeNPs effectively alleviate DON-induced intestinal epithelial barrier dysfunction in IPEC-J2 cells, which are closely associated with ERS-related PERK signaling pathway. This will provide a potential solution for prevention and control of DON in the aquaculture industry.

Sodium butyrate alleviates deoxynivalenol-induced porcine intestinal barrier disruption by promoting mitochondrial homeostasis via PCK2 signaling.

Deoxynivalenol (DON) is one of the most plentiful trichothecenes occurring in food and feed, which brings severe health hazards to both animals and humans. This study aims to investigate whether sodium butyrate (NaB) can protect the porcine intestinal barrier from DON exposure through promoting mitochondrial homeostasis. In a 4-week feeding experiment, 28 male piglets were allocated according to a 2 by 2 factorial arrangement of treatments with the main factors including supplementation of DON (< 0.8 vs. 4.0 mg/kg) and NaB (0.0 vs. 2 g/kg) in a corn/soybean-based diet. Dietary NaB supplementation mitigated the damaged mitochondrial morphology within the jejunal mucosa and the disrupted gut epithelial tight junctions irritated by DON. In IPEC-J2 cells, we found efficient recovery of the intestinal epithelial barrier occurred following NaB administration. This intestinal barrier reparation was facilitated by NaB-induced PCK2-mediated glyceroneogenesis and restoration of mitochondrial structure and function. In conclusion, we elucidated a mechanism of PCK2-mediated improvement of mitochondrial function by NaB to repair porcine intestinal barrier disruption during chronic DON exposure. Our findings highlight the promise of NaB for use in protecting against DON-induced gut epithelial tight junction disruption in piglets.

Vitamin D Supplementation Impacts Calcium and Phosphorus Metabolism in Piglets Fed a Diet Contaminated with Deoxynivalenol and Challenged with Lipopolysaccharides.

Using alternative feed ingredients in pig diets can lead to deoxynivalenol (DON) contamination. DON has been shown to induce anorexia, inflammation, and-more recently-alterations in the vitamin D, calcium, and phosphorus metabolisms. Adding vitamin D supplementation in the form of vitamin D3 and 25-OH-D3 to the feed could modify the effects of DON in piglets. In this study, vitamin D3 or 25-OH-D3 supplementation was used in a control or DON-contaminated treatment. A repetitive exposure over 21 days to DON in the piglets led to disruptions in the vitamin D, calcium, and phosphorus metabolisms, resulting in a decreased growth performance, increased bone mineralization, and the downregulation of genes related to calcium and to phosphorus intestinal and renal absorption. The DON challenge also decreased blood concentrations of 25-OH-D3, 1,25-(OH)2-D3, and phosphate. The DON contamination likely decreased the piglets' vitamin D status indirectly by modifying the calcium metabolism response. Vitamin D supplementations did not restore vitamin D status or bone mineralization. After a lipopolysaccharide-induced inflammatory stimulation, feeding a 25-OH-D3 supplementation increased 25-OH-D3 concentration and 1,25-(OH)2-D3 regulations during the DON challenge. DON contamination likely induced a Ca afflux by altering the intestinal barrier, which resulted in hypercalcemia and hypovitaminosis D. The vitamin D supplementation could increase the calcitriol production to face the combined LPS and DON challenge.

Combination of glycyrrhizic acid and compound probiotics alleviates deoxynivalenol-induced damage to weaned piglets.

Deoxynivalenol (DON) can affect health and growth performance of pigs, resulting in significant economic losses in swine production. The aim of this study was to investigate the effect of glycyrrhizic acid combined with compound probiotics, i.e. Enterococcus faecalis plus Saccharomyces cerevisiae (GAP) on improving growth performance, intestinal health and its fecal microbiota composition change of piglets challenged with DON. A total of 160 42-day-old weaned piglets (Landrace × Large White) were used and the experimental period was 28 d. The results showed that supplementing GAP in the diet significantly improved the growth performance of piglets challenged with DON and alleviate DON-induced intestinal damage by reducing ALT, AST and LDH concentrations in serum, increasing the morphological parameters of jejunum, and decreasing DON residues in serum, liver and feces. Moreover, GAP could significantly decrease the expressions of inflammation and apoptosis genes and proteins (IL-8, IL-10, TNF-α, COX-2, Bax, Bcl-2 and Caspase 3), and increase the expressions of tight-junction proteins and nutrient transport factor genes and proteins (ZO-1, Occludin, Claudin-1, ASCT2 and PePT1). In addition, it was also found that GAP supplementation could significantly increase the diversity of gut microbiota, maintain microbial flora balance and promote piglet growth by significantly increasing the abundance of beneficial bacterium such as Lactobacillus and reducing the abundance of harmful bacterium such as Clostridium_sensu_stricto_1. In conclusion, GAP addition to piglet diets contaminated with DON could significantly promote the health and growth performance of piglets though alleviating DON-induced hazards. This study provided a theoretical basis for the application of GAP to alleviate DON toxicity for animals.

Dietary taurine supplementation counteracts deoxynivalenol-induced liver injury via alleviating oxidative stress, mitochondrial dysfunction, apoptosis, and inflammation in piglets.

Deoxynivalenol (DON), as a widespread Fusarium mycotoxin in cereals, food products, and animal feed, is detrimental to both human and animal health. The liver is not only the primary organ responsible for DON metabolism but also the principal organ affected by DON toxicity. Taurine is well known to display various physiological and pharmacological functions due to its antioxidant and anti-inflammatory properties. However, the information regarding taurine supplementation counteracting DON-induced liver injury in piglets is still unclear. In our work, twenty-four weaned piglets were subjected to four groups for a 24-day period, including the BD group (a basal diet), the DON group (3 mg/kg DON-contaminated diet), the DON+LT group (3 mg/kg DON-contaminated diet + 0.3% taurine), and the DON+HT group (3 mg/kg DON-contaminated diet + 0.6% taurine). Our findings indicated that taurine supplementation improved growth performance and alleviated DON-induced liver injury, as evidenced by the reduced pathological and serum biochemical changes (ALT, AST, ALP, and LDH), especially in the group with the 0.3% taurine. Taurine could counteract hepatic oxidative stress in piglets exposed to DON, as it reduced ROS, 8-OHdG, and MDA concentrations and improved the activity of antioxidant enzymes. Concurrently, taurine was observed to upregulate the expression of key factors involved in mitochondrial function and the Nrf2 signaling pathway. Furthermore, taurine treatment effectively attenuated DON-induced hepatocyte apoptosis, as verified through the decreased proportion of TUNEL-positive cells and regulation of the mitochondria-mediated apoptosis pathway. Finally, the administration of taurine was able to reduce liver inflammation due to DON, by inactivating the NF-κB signaling pathway and declining the production of pro-inflammatory cytokines. In summary, our results implied that taurine effectively improved DON-induced liver injury. The underlying mechanism should be that taurine restored mitochondrial normal function and antagonized oxidative stress, thereby reducing apoptosis and inflammatory responses in the liver of weaned piglets.

Effects of Dietary Milk Thistle (Silybum marianum) Supplementation in Ducks Fed Mycotoxin-Contaminated Diets.

The medicinal plant milk thistle (Silybum marianum) has been widely used due to its hepatoprotective properties. The main objective of our study was to investigate the health protective effects of dietary milk thistle seed (MS), oil (MO), and seed cake (MSC) in ducks fed diets naturally contaminated with deoxynivalenol (DON; 3.43-3.72 mg/kg feed) and zearalenone (ZEN; 0.46-0.50 mg/kg feed). Female White Hungarian ducks were randomly allocated to four dietary treatments consisting of the control diet (C), the control diet supplemented with 0.5% MS, 0.5% MSC, or 0.1% MO. The feeding of experimental diets did not result in mortality cases, clinical signs of mycotoxicosis, or in differences of clinical chemistry values of blood serum. The positive effect of MO on vacuolar hepatocyte degeneration exceeded that of the MSC on d14 and both MS and MSC on d42. Each treatment was equally effective in the decrease of the severity of solitary cell death and infiltration of lympho- and histiocytes in the liver on d28 as well as in the prevention of lymphocyte depletion in the spleen and bursa of Fabricius on d14. In conclusion, the applied treatments have been proven effective in the prevention of histopathological changes caused by DON and ZEN.

Dietary Catalase Supplementation Alleviates Deoxynivalenol-Induced Oxidative Stress and Gut Microbiota Dysbiosis in Broiler Chickens.

Catalase (CAT) can eliminate oxygen radicals, but it is unclear whether exogenous CAT can protect chickens against deoxynivalenol (DON)-induced oxidative stress. This study aimed to investigate the effects of supplemental CAT on antioxidant property and gut microbiota in DON-exposed broilers. A total of 144 one-day-old Lingnan yellow-feathered male broilers were randomly divided into three groups (six replicates/group): control, DON group, and DON + CAT (DONC) group. The control and DON group received a diet without and with DON contamination, respectively, while the DONC group received a DON-contaminated diet with 200 U/kg CAT added. Parameter analysis was performed on d 21. The results showed that DON-induced liver enlargement (p < 0.05) was blocked by CAT addition, which also normalized the increases (p < 0.05) in hepatic oxidative metabolites contents and caspase-9 expression. Additionally, CAT addition increased (p < 0.05) the jejunal CAT and GSH-Px activities coupled with T-AOC in DON-exposed broilers, as well as the normalized DON-induced reductions (p < 0.05) of jejunal villus height (VH) and its ratio for crypt depth. There was a difference (p < 0.05) in gut microbiota among groups. The DON group was enriched (p < 0.05) with some harmful bacteria (e.g., Proteobacteria, Gammaproteobacteria, Enterobacteriales, Enterobacteriaceae, and Escherichia/Shigella) that elicited negative correlations (p < 0.05) with jejunal CAT activity, and VH. DONC group was differentially enriched (p < 0.05) with certain beneficial bacteria (e.g., Acidobacteriota, Anaerofustis, and Anaerotruncus) that could benefit intestinal antioxidation and morphology. In conclusion, supplemental CAT alleviates DON-induced oxidative stress and intestinal damage in broilers, which can be associated with its ability to improve gut microbiota, aside from its direct oxygen radical-scavenging activity.

Glycyrrhizic Acid and Compound Probiotics Supplementation Alters the Intestinal Transcriptome and Microbiome of Weaned Piglets Exposed to Deoxynivalenol.

Deoxynivalenol (DON) is a widespread mycotoxin that affects the intestinal health of animals and humans. In the present study, we performed RNA-sequencing and 16S rRNA sequencing in piglets after DON and glycyrrhizic acid and compound probiotics (GAP) supplementation to determine the changes in intestinal transcriptome and microbiota. Transcriptome results indicated that DON exposure altered intestinal gene expression involved in nutrient transport and metabolism. Genes related to lipid metabolism, such as PLIN1, PLIN4, ADIPOQ, and FABP4 in the intestine, were significantly decreased by DON exposure, while their expressions were significantly increased after GAP supplementation. KEGG enrichment analysis showed that GAP supplementation promoted intestinal digestion and absorption of proteins, fats, vitamins, and other nutrients. Results of gut microbiota composition showed that GAP supplementation significantly improved the diversity of gut microbiota. DON exposure significantly increased Proteobacteria, Actinobacteria, and Bacillus abundances and decreased Firmicutes, Lactobacillus, and Streptococcus abundances; however, dietary supplementation with GAP observably recovered their abundances to normal. In addition, predictive functions by PICRUSt analysis showed that DON exposure decreased lipid metabolism, whereas GAP supplementation increased immune system. This result demonstrated that dietary exposure to DON altered the intestinal gene expressions related to nutrient metabolism and induced disturbances of intestinal microbiota, while supplementing GAP to DON-contaminated diets could improve intestinal health for piglets.

Dietary supplementation with selenium nanoparticles-enriched Lactobacillus casei ATCC 393 alleviates intestinal barrier dysfunction of mice exposed to deoxynivalenol by regulating endoplasmic reticulum stress and gut microbiota.

Deoxynivalenol (DON), a secondary product of Fusarium metabolism, is common in wheat, corn, barley and other grain crops, posing a variety of adverse effects to environment, food safety, human and animal health. The absorption of DON mainly occurs in the proximal part of the small intestine, which can induce intestinal mucosal epithelial injury, and ultimately affect the growth performance and production performance of animals. This study was conducted to investigate the protective effects of selenium nanoparticles (SeNPs)-enriched Lactobacillus casei ATCC 393 (L. casei ATCC 393) on intestinal barrier function of C57BL/6 mice exposed to DON and its association with endoplasmic reticulum stress (ERS) and gut microbiota. The results showed that DON exposure increased the levels of interleukin-6 (IL-6) and interleukin-8 (IL-8), decreased the levels of interleukin-10 (IL-10) and transforming growth factor beta (TGF-ß), caused a redox imbalance and intestinal barrier dysfunction, decreased the mRNA levels of endoplasmic reticulum- resident selenoproteins, activated ERS-protein kinase R-like endoplasmic reticulum kinase (PERK) signaling pathway, altered the composition of the gut microbiota and decreased short-chain fatty acids (SCFAs) content. Dietary supplementation with SeNPs-enriched L. casei ATCC 393 can effectively protect the integrity of intestinal barrier function by reducing inflammatory response, enhancing the antioxidant capacity, up-regulating the mRNA levels of endoplasmic reticulum-resident selenoproteins, inhibiting the activation of PERK signaling pathway, reversing gut microbiota dysbiosis and increasing the content of SCFAs in mice exposed to DON. In conclusion, dietary supplementation with SeNPs-enriched L. casei ATCC 393 effectively alleviated intestinal barrier dysfunction induced by DON in C57BL/6 mice, which may be closely associated with the regulation of ERS and gut microbiota.

Evaluation of dietary mycotoxin control strategies on nursery pig growth performance and blood measures.

A total of 4,318 pigs (337 × 1,050, PIC; initially 6.5 ± 0.08 kg) were used in a 35-day study to evaluate dietary mycotoxin control strategies on nursery pig performance and blood measures. Pigs were weaned at approximately 21 d of age and randomly allotted to 1 of 5 dietary treatments in a randomized complete block design with blocking structure including sow farm origin, date of entry into facility, and average pen BW. A total of 160 pens were used with 80 double-sided 5-hole stainless steel fence line feeders, with feeder serving as the experimental unit. For each feeder, 1 pen contained 27 gilts and 1 pen contained 27 barrows. There were 16 replications per dietary treatment. A common phase 1 diet was fed to all pigs in pelleted form for 7 day prior to treatment diets. Experimental treatments were fed from days 7 to 42 after weaning (days 0 to 35 of the study) and included a low deoxynivalenol (DON) diet (1.12 ± 0.623 mg/kg), high DON diet (2.34 ± 1.809 mg/kg), high DON+ 0.50% sodium metabisulfite (SMB), high DON+ one of two mitigating products; 0.30% Technology1, or 0.30% Technology1+. Technology1 and 1+ are comprised of clays, yeast cell wall components, and a blend of plant extracts. Technology1+ also contains SMB. Overall (days 0 to 35), pigs fed high DON had decreased (P < 0.05) final BW, ADG, and ADFI compared with low DON. Additionally, pigs fed high DON+SMB had increased (P < 0.05) ADG compared with all other treatments. An improvement (P < 0.05) in G:F was observed in pigs fed high DON + SMB or high DON + Technology1+ compared with the low DON or high DON + Technology1 diets with high DON diets intermediate. Pigs fed high DON + SMB or high DON + Technology1 diets had reduced (P < 0.05) total removals and mortality compared with pigs fed low DON diets with high DON and high DON + Technology1+ intermediate. Liquid chromatography/mass spectrometry analysis of circulating blood collected on day 35 revealed that pigs fed high DON or high DON + Technology1 had increased (P < 0.05) DON concentrations compared to low DON with high DON + SMB and high DON + Technology1+ intermediate. In summary, pigs fed high DON diets had reduced performance compared with pigs fed low DON. Sodium metabisulfite in high DON diets provided a benefit in growth performance with ADG and G:F exceeding growth performance in the low DON diet while, the improved G:F ratio combined with other immunometabolic changes (gamma glutamyltransferase and creatine kinase) associated with Technology1+ warrant further investigation.

Dihydroartemisinin alleviates deoxynivalenol induced liver apoptosis and inflammation in piglets.

Deoxynivalenol (DON) is one of the mycotoxins that contaminate cereals and feed, thereby endangering human and animal health. Dihydroartemisinin (DHA), a derivative of artemisinin, has anti-inflammatory and antioxidant functions in addition to anti-malaria and anti-cancer. The purpose of this study was to investigate the effects of DHA on alleviating liver apoptosis and inflammation induced by DON in piglets. The experimental design followed a 2 (normal diet and DON-contaminated diet) × 2 (with and without supplementation of DHA) factorial arrangement. 36 weaned piglets were subjected to a 21-day experiment. Results showed that DON increased ALT activity, the levels of TNF-α, IL-1ß and IL-2, and reduced the levels of total protein (TP) and albumin (ALB) in the serum. However, DHA decreased the levels of TNF-α, IL-1ß and IL-2, and increased the levels of TP and ALB. Also, DON decreased glutathione (GSH) content and catalase (CAT) activity, and increased methane dicarboxylic aldehyde (MDA) content. But GSH content was increased by DHA. In addition, DHA decreased DON-induced increase in apoptosis rate of hepatocytes. Furthermore, DON activated death receptor pathway to promote apoptosis by up-regulating the protein expression of FasL and caspase-3, and the mRNA expression of FasL, TNFR1, caspase-8, Bid, Bax, CYC and caspase-3. However, DHA reduced caspase-3 protein expression, as well as the mRNA expression of FADD, Bid, Bax, CYC and caspase-3. Besides, DON also activated TNF/NF-κB pathway to induce an inflammatory response by up-regulating TNF-α protein expression, and the mRNA expression of TNFR1, RIP1, IKKß, IκBα, IL-1ß and IL-8. Nevertheless, DHA reduced the mRNA expression of RIP1, IκBα, NF-κB, IL-1ß and IL-6, and the protein expression of TNF-α and NF-κB. In conclusion, DHA improved DON-induced negative effects on serum biochemical parameters and inflammatory cytokine levels, hepatic antioxidant capacity, hepatic apoptosis and inflammation.