Dietary Deoxynivalenol Research Articles

Necroptosis contributes to deoxynivalenol-induced liver injury and inflammation in weaned piglets

BackgroundThe aim of this study was to investigate the role of necroptosis in deoxynivalenol (DON)-induced liver injury and inflammation in weaned piglets.MethodsIn Exp. 1, 12 weaned piglets were divided into 2 groups including pigs fed basal diet and pigs fed diet contaminated with 4 mg/kg DON for 21 d. In Exp. 2, 12 weaned piglets were divided into 2 groups including control piglets and piglets given a gavage of 2 mg/kg body weight (BW) DON. In Exp. 3, 24 weaned piglets were used in a 2 × 2 factorial design and the main factors including necrostatin-1 (Nec-1) (DMSO or 0.5 mg/kg BW Nec-1) and DON challenge (saline or 2 mg/kg BW DON gavage). On 21 d in Exp. 1, or at 6 h post DON gavage in Exp. 2 and 3, pigs were killed for blood samples and liver tissues. Liver histology, blood biochemical indicators, and liver inflammation and necroptosis signals were tested.ResultsDietary or oral gavage with DON caused liver morphological damage in piglets. Dietary DON led to hepatocyte damage indicated by increased aspartate transaminase (AST) activity and AST/alanine aminotransferase (ALT) ratio, and DON gavage also caused hepatocyte damage and cholestasis indicated by increased AST and alkaline phosphatase (AKP) activities. Dietary DON caused liver necroptosis indicated by increased protein abundance of total receptor interacting protein kinase 3 (t-RIP3) and total mixed lineage kinase domain-like protein (t-MLKL). Moreover, DON gavage increased mRNA expression of interleukin (IL)-6 and IL-1β in liver. DON gavage also induced liver necroptosis demonstrated by increased protein abundance of t-RIP3, phosphorylated-RIP3 (p-RIP3), t-MLKL and p-MLKL. However, pretreatment with Nec-1, a specific inhibitor of necroptosis, inhibited liver necroptosis indicated by decreased protein expression of t-RIP3, p-RIP3, t-MLKL and p-MLKL. Nec-1 pretreatment reduced liver morphological damage after DON gavage. Pretreatment with Nec-1 also attenuated liver damage induced by DON indicated by decreased activities of AST and AKP. Furthermore, Nec-1 pretreatment inhibited liver mRNA expression of IL-6 and IL-1β after DON challenge.ConclusionsOur data demonstrate for the first time that necroptosis contributes to DON-induced liver injury and inflammation in piglets.

Chronic dietary deoxynivalenol exposure interferes the intestinal microbial community structure and antibiotic resistome in laying hens

Antibiotic resistance genes (ARGs) are critical emerging pollutants that have attracted considerable attention. Deoxynivalenol (DON) is one of the most prevalent mycotoxins in cereal crops worldwide, arising severe health hazards to both humans and animals. Even if numerous researches argue in favor of a notorious influence of DON on the gut, the effects of dietary DON exposure on the ARG profile in poultry intestine remain obscure. In this study, two separate feeding experiments using Jing Tint 6 laying hens exposed to 4.5 or 9.0 mg/kg DON were performed to explore the impact of dietary DON exposure on the microbial community structure and the profiles of ARGs in the intestine via 16S rDNA sequencing and metagenomics sequencing, respectively. In addition, growth performance and intestinal barrier function were also determined to assess the feasibility of using DON-contaminated feedstuffs inappropriate for pigs’ consumption in laying hens. Chronic ingestion of DON at 9.0 mg/kg did not alter zootechnical parameters. However, histomorphological impairments were observed in liver and jejunum. Additionally, metagenomic sequencing revealed that dietary DON exposure at 9.0 mg/kg level dramatically changed the gut microbial structure and shifted the ARG profile. The abundance of tetracycline ARG subtype in the layer cecum was decreased, whereas the abundance of vancomycin ARG subtype was increased upon DON exposure. Co-occurrence network analysis identified that Prevotella was the major ARG host in the intestine of laying hens. In summary, our findings demonstrated that DON-contaminated feedstuffs inappropriate for pigs’ consumption should be prudently used in hen production, and shed new light on the interactions between mycotoxins and ARGs in the poultry intestine.

Lactiplantibacillus plantarum JM113 alleviates deoxynivalenol induced intestinal damage by microbial modulation in broiler chickens

Deoxynivalenol (DON) contamination causes the grievous injury in public and animal health, poultry suffer from the greater toxin challenge. Probiotic have been considered as a potential way to mitigate the deleterious effects of DON. In this study, a total of 144 1-day-old Arbor Acres chickens were randomly assigned into 3 groups: control group, DON group (5 mg/kg DON diet), DJ group (1×109 cfu Lactiplantibacillus plantarum JM113/kg DON diet). The results showed that Lactiplantibacillus plantarum JM113 (L. plantarum JM113) increased the growth performance of 21-day-old broilers that challenged by the DON (P < 0.05), and the DON-induced disorder of jejunal morphology was recovered in DJ group (P < 0.05). Compared with the DON group, the mRNA and protein levels of Nrf2 and NQO-1 were upregulated in jejunum of DJ group broilers (P < 0.05). Meanwhile, administration of L. plantarum JM113 effectively increased the expression level of barrier-related genes, and the protein abundance of occludin and claudin1 (P < 0.05). L. plantarum JM113 restored the mRNA and protein abundance of PCNA, and proliferation-linked gene (Lgr5 and Bmi1) expression levels in jejunum of DON-insulted broilers (P < 0.05). Furthermore, administration of L. plantarum JM113 significantly enhanced the relative abundance of s_Limosilactobacillus_reuteri in jejuna of DON-challenged broilers (P < 0.05). Spearman correlation analysis showed that s_Limosilactobacillus_reuteri was positively associated with the jejunal barrier related genes (P < 0.05). In conclusion, L. plantarum JM113 alleviated the toxic effects of DON by regulating the jejunal function through microbial adjustment. Our findings proposed a viable approach to mitigating the adverse effects of deoxynivalenol exposure in broilers.

Effects of dietary deoxynivalenol on growth performance and organ accumulation of growing pigs.

The present study aimed to study effects of a chronic feeding of deoxynivalenol (DON) on growth performance, organ weight, organ DON accumulation, and blood parameters in pigs. Forty-eight castrated male pigs with a body weight of 10.4 kg (standard deviation = 1.7) were assigned to one of 2 diet groups in a randomized complete block design with 6 blocks of pens per diet and 4 pigs per pen. A corn-soybean meal-based control diet was prepared to contain a low DON concentration of 0.28 mg/kg. Corn distillers dried grains with solubles naturally contaminated with DON were used at 30.0% to prepare a contaminated diet with a high DON concentration of 1.8 mg/kg. During the 56-day experimental period, body weight and feed intake were recorded every 14 days. A pig from each pen was euthanized for the collection of organs and muscle every 14 days. Gain:feed in pigs fed the contaminated diet during days 14 to 28 and days 28 to 42 were less (p<0.05) compared with the control group. As increasing feeding period, the DON concentrations in fresh liver increased during days 14 to 28 and then decreased during the subsequent periods in the DON group, whereas the DON concentrations in fresh liver were constant during the experimental period in the control group (quadratic interaction p = 0.049). The DON concentration in the kidneys in the DON group was greater (p = 0.002) than that in the control group regardless of feeding period. On day 56, the granulocyte count in the DON group was less (p = 0.035) than the control group. A chronic feeding of DON for 14 to 42 days decreased gain:feed in pigs, and dietary DON naturally contaminated in corn distillers dried grains with solubles accumulated in the liver during days 14 to 28.

Are Infants and Children at Risk of Adverse Health Effects from Dietary Deoxynivalenol Exposure? An Integrative Review.

Deoxynivalenol (DON) is a foodborne mycotoxin produced by Fusarium molds that commonly infect cereal grains. It is a potent protein synthesis inhibitor that can significantly impact humans' gastrointestinal, immune, and nervous systems and can alter the microbiome landscape. Low-dose, chronic exposure to DON has been found to stimulate the immune system, inhibit protein synthesis, and cause appetite suppression, potentially leading to growth failure in children. At higher doses, DON has been shown to cause immune suppression, nausea, vomiting, abdominal pain, headache, diarrhea, gastroenteritis, the malabsorption of nutrients, intestinal hemorrhaging, dizziness, and fever. A provisional maximum tolerable daily intake (PMTDI) limit of 1 µg/kg/body weight has been established to protect humans, underscoring the potential health risks associated with DON intake. While the adverse effects of dietary DON exposure have been established, healthcare communities have not adequately investigated or addressed this threat to child health, possibly due to the assumption that current regulatory exposure limits protect the public appropriately. This integrative review investigated whether current dietary DON exposure rates in infants and children regularly exceed PMTDI limits, placing them at risk of negative health effects. On a global scale, the routine contamination of cereal grains, bakery products, pasta, and human milk with DON could lead to intake levels above PMTDI limits. Furthermore, evidence suggests that other food commodities, such as soy, coffee, tea, dried spices, nuts, certain seed oils, animal milk, and various water reservoirs, can be intermittently contaminated, further amplifying the scope of the issue. Better mitigation strategies and global measures are needed to safeguard vulnerable youth from this harmful toxicant.

A method for estimating the outer exposure of dairy cows to deoxynivalenol (DON) and zearalenone (ZEN) as a precondition for risk assessment based on inner exposure with toxin residue levels in blood and urine as indicators

DON and ZEN residues in the blood and urine of dairy cows can be used to predict the outer exposure to DON and ZEN expressed per kilogram diet for a risk evaluation based on comparisons to critical dietary concentrations. This method was used to evaluate the exposure of dairy cows from 12 farms located in Brandenburg, Germany, fed rations with unknown DON and ZEN concentrations (N = 244). The corresponding diet concentrations predicted by different methods from analyzed blood and urine samples varied significantly amongst farms from 0 to 1.6 mg/kg for DON and 0 to 3.0 mg/kg for ZEN at a reference dry matter content of 88% but independently of lactational state (post-partum vs. early lactation). This significant variation was noticed below the critical dietary DON concentration of 5 mg/kg, while the ZEN concentration in one farm exceeded the critical ZEN level of 0.5 mg/kg markedly. Predicted DON concentrations of rations increased with the proportion of maize silage, while the high ZEN concentration found in one farm was most likely related to a higher proportion of sugar beet pulp supposedly highly contaminated by ZEN. Exceeding the critical dietary ZEN concentration and significant variations in DON contents below the critical level was not related to performance, reproductive performance, and health-related traits of cows. For a more consistent evaluation of possible associations between the inner exposure of cows to DON and ZEN, more frequent longitudinal observations of both mycotoxin residue levels and performance and health traits are required.

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.

Effects of dietary mycotoxins and mycotoxin adsorbent additives on production performance, hematological parameters, and liver histology in juvenile Nile tilapia (Oreochromis niloticus)

Mycotoxins are fungal secondary metabolites that can adversely affect animals consuming contaminated feeds. This 71-day feeding trial was conducted to assess the effects of dietary deoxynivalenol plus zearalenone (DON+ZEN = 1.6 + 0.3 ppm), and fumonisins (FUM = 15 ppm), and three adsorbent additives on the production performance, hematological parameters, and liver histology of juvenile Nile tilapia. A mycotoxin-free diet (Control) formulated to contain 35% protein and 8% lipid was spiked with either DON+ZEN or FUM using contaminated corn meals replacing portions of non-spiked corn. Subsequently, three out of four DON+ZEN- and FUM-spiked diets were supplemented (0.5%) with an adsorbent. The research was carried out in a recirculating water system (2,500 L) with a controlled temperature of (25.9 ± 1.1°C), feeding was carried out twice a day at rates ranging from 5 to 8%. The experiment included nine treatments with five replications, each experimental unit consisting of an aquarium with a useful volume of 75-L and fifteen juvenile Nile tilapia (average initial weight of 4.0 ± 0.1 g). Mycotoxin-spiked diets without added adsorbent supported lower final biomass and survival of Nile tilapia relative to control and adsorbent containing diets (P ≤ 0.05). Histological examinations revealed liver inflammation evidenced by lymphocytic infiltration adjacent to pancreatic tissue in fish fed mycotoxin-spiked diets without added adsorbent. Mycotoxin contamination significantly increased HSI (hepato somatic index), which was reverted to the Control value or reduced further by adsorbent addition. Lowest and intermediate hematocrit values were observed in groups fed mycotoxin-spiked diets without and with added adsorbents, respectively. Our results reinforce the importance of using adsorbents and the need to investigate the effect of sub-lethal concentrations of mycotoxins in aquaculture feeds.

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.

Inactivation of zearalenone (ZEN) and deoxynivalenol (DON) in complete feed for weaned piglets: Efficacy of ZEN hydrolase ZenA and of sodium metabisulfite (SBS) as feed additives

Female pigs respond sensitive both to DON and ZEN with anorexia and endocrine disruption, respectively, when critical diet concentrations are exceeded. Therefore, the frequent co-contamination of feed by DON and ZEN requires their parallel inactivation. The additive ZenA hydrolyzes ZEN while SBS inactivates DON through sulfonation. Both supplements were simultaneously added (+, 2.5 g SBS and 100 U ZenA/kg) to a control diet (CON−, 0.04 mg DON and < 0.004 mg ZEN/kg; CON+, 0.03 mg DON and < 0.004 mg ZEN/kg) and a Fusarium toxin contaminated diet (FUS−, 2.57 mg DON and 0.24 mg ZEN/kg; FUS+, 2.04 mg DON and 0.24 mg ZEN/kg). The 4 diets were fed to 20 female weaned piglets each (6 kg initial body weight) for 35 days; the piglets were sacrificed thereafter for collecting samples. Supplements improved performance and modified metabolism and hematology independent of dietary DON contamination. The mechanisms behind these changes could not be clarified and require further consideration. SBS reduced DON concentration in feed by approximately 20% and to the same extent in blood plasma and urine suggesting that no further DON sulfonate formation occurred in the digestive tract before absorbing DON in the upper digestive tract or that additionally formed DON sulfonates escaped absorption. DON sulfonates were detected in feces suggesting that unabsorbed DON sulfonates reached feces and/or that unabsorbed DON was sulfonated in the hindgut. The observed reduction rate of 20% was evaluated to be insufficient for feeding practice. Galenic form of SBS added to dry feed needs to be improved to support the DON sulfonation in the proximal digestive tract.ZenA was active in the digestive tract as demonstrated by the presence of its hydrolyzed none-estrogenic reaction products hydrolyzed ZEN (HZEN) and decarboxylated and hydrolyzed ZEN (DHZEN) both in feces, systemic circulation, and urine of group FUS+ compared to group FUS−. The presence of these hydrolysis products was paralleled by a significant decrease in high-estrogenic ZEN concentrations which, in turn, was related to a decrease in relative weights of uteri and ovaries when compared to group FUS−. Thus, ZenA was proven to be effective; both in terms of biomarkers and biological effects.

Effect of Lactobacillus sp. and yeast supplementation on performance and some blood attributes in deoxynivalenol-challenged broiler chickens

An experiment was conducted to evaluate the effect of different concentrations of probiotic (Lactobacillus sp.) and yeast (Saccharomycese cerevisiae) on performance, organ attributes and blood traits in broiler chickens. A total of 360 one-day-old female broiler chickens (Hubbard)® were allocated to 9 treatments and four replicates (10 birds per replication). The trail was performed in a completely randomized design (3 × 3 factorial arrangement) to examine the interaction effect of three concentrations of Lactobacillus sp. (0, 0.2 and 0.4 g/kg) and yeast (0, 0.75 and 1.5 g/kg) in deoxynivalenol (DON)-contaminated diets. The results showed that consumption of Lactobacillus sp. and yeast in DON-contaminated diets did not have a significant effect on broiler performance except for feed intake during starter period which was enhanced by yeast administration (P < 0.05). Increasing the Lactobacillus sp. content also reduced (P = 0.05) the proportional liver weight. Administration of Lactobacillus sp. to DON diets increased total protein, albumin and globulin concentrations (P < 0.05). Calcium and creatinine were influenced by yeast and Lactobacillus sp., respectively. Yeast (1.5 g/kg) and Lactobacillus sp. (0.2 g/kg) and combination of two additives (1.5 × 0.2) led to lower triglyceride concentration compared to DON group (P < 0.05). The DON diet increased aspartate amino transferase (AST) and lactate dehydrogenase (LDH) enzymes concentrations; while, inclusion of 0.4 g/kg Lactobacillus sp. to DON diet decreased AST and LDH enzymes concentrations (P < 0.05). In conclusion, administration of Lactobacillus sp. and yeast could not influence the performance of DON-fed birds; but these additives could reduce negative effects of DON on enzyme activities and some blood attributes.

Subclinical doses of dietary fumonisins and deoxynivalenol cause cecal microbiota dysbiosis in broiler chickens challenged with Clostridium perfringens.

Fusarium toxins are one of the most common contaminants in poultry diets. The co-occurrence of fumonisins (FUM) and deoxynivalenol (DON), even at a subclinical dose, negatively affects the growth performance, intestinal integrity and induce subclinical necrotic enteritis in broiler chickens. Loss of gut integrity can be expected to alter the intestinal microbiota's composition. The objective of this study was to identify the effects of combined FUM and DON on the cecal microbiome profile and predicted metabolic functions and a short chain fatty acid profile in broilers challenged with Clostridium perfringens. A total of 240 1 day-old chicks were randomly assigned to two treatments: a control diet and the control diet with 3 mg/kg FUM + 4 mg/kg DON each with eight replications. All the birds were received cocci vaccine at d0. All birds in both treatment groups were challenged with C. perfringens 1 × 108 CFU via feed on d 19 and 20 to achieve 5% mortality. On d 35, the FUM and DON contaminated diet numerically (P = 0.06) decreased the body weight gain (BWG) by 84 g compared to the control group. The bacterial compositions of the cecal contents were analyzed by sequencing the V3-V4 region of the 16S rRNA gene. Overall, microbial richness and diversity increased (P < 0.02) during the studied period (d 21-35). Cecal contents of birds in the FUM + DON group had greater (P < 0.05) microbial evenness and diversity (Shannon index) compared to the control group. FUM + DON exposure decreased (P = 0.001) the relative abundance of Proteobacteria in the cecal content, compared to the control group. The combined FUM + DON significantly increased the relative abundance of the Defluviitaleaceae and Lachnospiraceae families (P < 0.05) but decreased the abundances of the Moraxellaceae and Streptococcaceae (P < 0.05) compared to the control group birds. At the genus level, FUM + DON exposure decreased (P < 0.05) Acinetobacter and Pseudomonas abundance and had a tendency (P = 0.08) to decrease Thermincola abundance compared to the control group. In the ileum, no NE-specific microscopic abnormalities were found; however, the tip of the ileal villi were compromised. The present findings showed that dietary FUM and DON contamination, even at subclinical levels, altered cecal microbial composition, dysregulated intestinal functions, and impaired the gut immune response, potentially predisposing the birds to necrotic enteritis.

Influence of deoxynivalenol-contaminated feed on the immune response of pigs after PRRSV vaccination and infection

The impact of the Fusarium mycotoxin deoxynivalenol (DON) on the immune response against porcine reproductive and respiratory syndrome virus (PRRSV) vaccination and infection was investigated. Forty-two weaned piglets were separated into seven groups and received three different diets: Low DON (1.09 ppm), High DON (2.81 ppm) or No DON. These three treatments were split further into either vaccinated (Ingelvac PRRSFLEX EU) and challenged with PRRSV 28 days post-vaccination, or only infected at day 28. A seventh group received no DON, no vaccination, and no infection. Two weeks after challenge infection, when pigs were euthanized, the number of IFN-γ producing lymphocytes in the blood of vaccinated animals was lower in pigs on High DON compared to animals on Low DON or No DON. Intracellular cytokine staining showed that vaccinated animals fed with the Low DON diet had higher frequencies of TNF-α/IFN-γ co-producing CD4+ T cells than the other two vaccinated groups, particularly in lung tissue. Vaccinated animals on High DON had similar viral loads in the lung as the non-vaccinated groups, but several animals of the Low DON or No DON group receiving vaccination had reduced titers. In these two groups, there was a negative correlation between lung virus titers and vaccine-specific TNF-α/IFN-γ co-producing CD4+ T cells located either in lung tissue or blood. These results indicate that after PRRSV vaccination and infection, high levels of DON negatively influence immune parameters and clearance of the virus, whereas low DON concentrations have immunomodulatory effects.

Lactoferrin Attenuates Intestinal Barrier Dysfunction and Inflammation by Modulating the MAPK Pathway and Gut Microbes in Mice

Deoxynivalenol (DON) is a major mycotoxin present in staple foods (particularly in cereal products) that induces intestinal inflammation and disrupts intestinal integrity. Lactoferrin (LF) is a multifunctional protein that contributes to maintaining intestinal homeostasis and improving host health. However, the protective effects of LF on DON-induced intestinal dysfunction remain unclear. This study aimed to investigate the effects of LF on DON-induced intestinal dysfunction in mice, and its underlying protective mechanism. Male BALB/c mice (5 wk old) with similar body weights were divided into 4 groups (n = 6/group) and treated as follows for 5 wk: Veh [peroral vehicle daily, commercial (C) diet]; LF (peroral 10 mg LF/d, C diet); DON (Veh, C diet containing 12 mg DON/kg); and LF + DON (peroral 10 mg LF/d, DON diet). Intestinal morphology, tight junction proteins, cytokines, and microbial community were determined. Data were analyzed by 2-factor ANOVA or Kruskal-Wallis test. The DON group exhibited lower final body weight (-12%), jejunal villus height (VH; -41%), and jejunal occludin expression (-36%), and higher plasma IL-1β concentration (+85%) and jejunal Il1b mRNA expression (+98%) compared with the Veh group (P < 0.05). In contrast, final body weight (+19%), jejunal VH (+49%), jejunal occludin (+53%), and intelectin 1 protein expression (+159%) were greater in LF + DON compared with DON (P < 0.05). Additionally, jejunal Il1b mRNA expression (-31%) and phosphorylation of p38 and extracellular signal regulated kinase 1/2 (-40% and - 38%) were lower in LF + DON compared with DON (P < 0.05). Furthermore, the relative abundance of Clostridium XIVa (+181%) and colonic butyrate concentration (+53%) were greater in LF + DON compared with DON (P < 0.05). Our study highlights a promising antimycotoxin approach using LF to alleviate DON-induced intestinal dysfunction by modulating the mitogen-activated protein kinase pathway and gut microbial community in mice.

Exposure assessment of urinary deoxynivalenol in pregnant women in Wuhan, China

Deoxynivalenol (DON) is a ubiquitous trichothecene mycotoxin in food. DON and its modified forms can cross the placental barrier and influence the foetus’ health. Limited information is available on exposure of dietary DON intake of pregnant women in China recently. We estimated the exposure of dietary DON intake of pregnant women in a large sample size (n = 2534) from China. The total DON (tDON) and free DON (fDON) biomarkers in urine were detected by liquid chromatography–tandem mass spectrometry. The mean concentration of tDON was 34.8 ng/mg creatinine, and the fDON was 15.9 ng/mg creatinine. The estimated exposure of dietary DON intake was 0.96–1.91 μg/kg bw/day, and the difference in exposure of DON between the first and second trimesters was statistically insignificant. Approximately 26%–60% of individuals exceeded the provisional maximum tolerable daily intake (PMTDI). The age, pre-pregnancy BMI, and the sampling seasons may be the risk factor for the occurrence of exceeding PMTDI. This survey is the first exposure biomarker for DON in a large sample size from pregnant women in China. We found that the dietary DON exposure in pregnant women was relatively high and particular concern should be paid to the DON exposure during pregnancy.

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.

111 Evaluation of Dietary Mycotoxin Control Strategies on Nursery Pig Growth Performance and Blood Measures

Abstract A total of 4,318 pigs (337×1050, PIC; initially 6.5±0.08kg) were used in a 35-d trial to evaluate dietary mycotoxin control strategies on nursery pig performance and blood measures. Pigs were weaned at 21-d of age and randomly allotted to 1 of 5 dietary treatments. 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/treatment. A common phase 1 diet was fed in pelleted form for 7-d prior to treatment diets. Experimental treatments were fed from d 7 to 42 after weaning (d0 to 35 of 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+ sodium metabisulfite (SMB), high DON+ 1 of 2 mitigating products; Technology1, or Technology1+. Technology1 and 1+ are comprised of clays, yeast cell wall components and a blend of plant extracts. Technology1+ also contains SMB. Overall (d0 to 35), pigs fed high DON had decreased (P &amp;lt; 0.05) final BW, ADG, and ADFI compared with low DON. Additionally, pigs fed high DON+SMB had increased (P&amp;lt;0.05) ADG compared with all other treatments. An increase (P &amp;lt; 0.05) in G:F was observed in pigs fed high DON+SMB or high DON+Technology1+ compared with low DON or high DON+Technology1 with high DON intermediate. Analysis of dried blood spots collected on d 35 revealed pigs fed high DON or high DON+Technology1 had increased (P &amp;lt; 0.05) DON concentrations compared with low DON with high DON+SMB and high DON+Technology1+ intermediate. In summary, pigs fed high DON had reduced performance compared with low DON. Sodium metabisulfite supplementation to high DON led to ADG and G:F that exceeded low DON, whereas Technology1+ resulted in similar ADG and improved G:F compared with low DON.

110 Dosage and not Time of Exposure to Deoxynivalenol Affects the Performance of Nursery Pigs Fed High Mycotoxin Diets up to 28 Days Post-Wean

Abstract The current experiment was conducted to determine if the dosage or timing of exposure to diets containing high deoxynivalenol (DON), a mycotoxin in a variety of feed ingredients, causes performance loss in nursery pigs. In total, 448 mixed-sex nursery pigs [initial BW = 6.18 ± 0.97 kg] weaned at 21 ± 1 d were allotted to 112 pens, with 4 pigs per pen, in a randomized complete block design. In a 3 x 2 + 1 factorial arrangement of treatments, diets with DON were fed continuously (CONT), at weeks 1 and 3 (WK13), and weeks 2 and 4 (WK24), targeting DON at 1.25 ppm fed (MED), or 2.5 ppm (HIGH), plus the positive control (CONTLOW) for 28 d. All pigs were fed a common, low DON diet from d 28 to 42 to complete the nursery phase. Pen weight and feed intake were measured on d 28 and 42 to calculate ADG and ADFI. Regardless of timing, d 28 BW decreased (P &amp;lt; 0.01) with feeding MED or HIGH diets compared with CONTLOW and markedly decreased (1.57 kg) in the HIGH. This was a response to the decreased ADG (P &amp;lt; 0.01) and ADFI (P &amp;lt; 0.01) from d 0 – 28 in MED or HIGH compared with CONTLOW and with HIGH compared with MED. Similarly, on d 42, performance metrics - BW (P &amp;lt; 0.01), ADG (P &amp;lt; 0.01), and ADFI (P &amp;lt; 0.01) were decreased in MED or HIGH compared with CONTLOW, with a 1.95 kg. decrease in BW in the HIGH compared with CONTLOW. A dose-response to DON was evident whereas, timing of exposure did not affect the performance metrics measured on d 28 or 42. Ultimately, exposure of nursery pigs to levels of DON over 1 ppm results in loss of performance, regardless of exposure timing.

Urinary deoxynivalenol as a biomarker of exposure in different age, life stage and dietary practice population groups.

The Fusarium mycotoxin deoxynivalenol (DON) and its modified forms are present in most samples of grain and grain-based products. Due to the widespread presence of DON in these highly consumed food commodities, nearly all individuals are exposed to DON. Previous estimates of the dietary DON intake in Norway indicated that children's dietary intake is close to or exceed the TDI of 1µg/kg bw/day for the sum of DON and three modified forms. One aim of the current study was to determine whether the concentrations of DON in morning urine differ between population groups like men, women, children, vegetarians, and pregnant women. An additional aim was to compare a set of models for estimating the dietary intake of DON based on urinary DON concentrations and also compare these models with DON-intakes estimated using food consumption data. DON and metabolites were detected in the morning urine from 256 out of 257 individuals and with concentrations in similar range as reported from other countries. Children have higher urinary DON-concentration than adults and elderly. The urinary DON-concentration in pregnant women and vegetarians did not differ from other adults. The estimated intake of DON was higher for children than for other age groups on a body weight basis. The correlations between different models for estimating DON-intake based on urinary concentration as well as based on individual food consumption were good (0.79-0.99), but with some outliers. We conclude that Norwegians are exposed to DON in the same range as reported from other countries and that children have a higher exposure than adults. Furthermore, we conclude that intake estimates based on urinary DON concentration is a useful tool for evaluation of the exposure at population level, but due to outliers, the estimates for individuals are uncertain. There are also uncertainties in intake estimates both from food consumption and from urinary DON concentration, and we could not conclude on which approach provides the most accurate exposure estimate.

Occurrence and Risk Assessment of Dietary Exposure to Deoxynivalenol in Wheat-Based Products Based Different Wheat-Producing Area for the Inhabitants in Shanghai, China.

Deoxynivalenol (DON) is one of the major mycotoxins that contaminate cereals. In this study, we determined the DON level in wheat-based products from Chinese five main production areas collected in Shanghai and calculated the daily intake of DON for inhabitants using the point evaluation and the probabilistic evaluation based on Monte Carlo simulation. The results showed the positive rates of DON in the products were higher than 80.0%, with the concentrations ranging from 41.8 to 1110 µg/kg. The estimated mean daily intakes of DON for 7- to 10-year-old children and adults groups were below 1 µg/kg bw/day, the provisional maximum tolerable daily intake (PMTDI) set by the Joint FAO/WHO Expert Committee on Food Additives (JECFA), suggesting no health risks for the consumers. However, the 99th percentiles of dietary DON exposures for children and adults exceeded the PMTDI, indicating adverse health effects might occur if the two groups intake highly contaminated wheat-based products. The potential health risks for the two groups exposed to DON in the wheat-based products from the Middle and Lower Yangtze Valley (MLYV) were higher than those from the other areas in China.