Strong Alterations in the Sphingolipid Profile of Chickens Fed a Dose of Fumonisins Considered Safe.
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ABSTRACT:
SUBMITTER: Tardieu D
PROVIDER: S-EPMC8619408 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:In chickens, the effect of mycotoxins, especially fumonisins (FB), in the gastrointestinal tract (GIT) is not well documented. Thus, this study in broiler chicks determined the effects of consuming diets prepared with Fusarium verticillioides culture material containing FB on intestinal gene expression and on the sphinganine (Sa)/sphingosine (So) ratio (Sa/So; a biomarker of FB effect due to disruption of sphingolipid metabolism). Male broilers were assigned to 6 diets (6 cages/diet; 6 birds/cage) from hatch to 20 days containing 0.4, 5.6, 11.3, 17.5, 47.8, or 104.8 mg FB/kg diet. Exposure to FB altered the Sa/So ratio in all tissues analyzed, albeit to varying extents. Linear dose-responses were observed in the kidney, jejunum and cecum. The liver and the ileum were very sensitive and data fit a cubic and quadratic polynomial model, respectively. Gene expression in the small intestine revealed low but significant upregulations of cytokines involved in the pro-inflammatory, Th1/Th17 and Treg responses, especially at 10 days of age. Interestingly, the cecal tonsils exhibited a biphasic response. Unlike the sphingolipid analysis, the effects seen on gene expression were not dose dependent, even showing more effects when birds were exposed to 11.3 mg FB/kg. In conclusion, this is the first report on the disruption of the sphingolipid metabolism by FB in the GIT of poultry. Further studies are needed to reach conclusions on the biological meaning of the immunomodulation observed in the GIT, but the susceptibility of chickens to intestinal pathogens when exposed to FB, at doses lower than those that would cause overt clinical symptoms, should be addressed.
| S-EPMC4417966 | biostudies-literature
Project description:Fumonisins (FB) are among the most frequently detected mycotoxins in feedstuffs and finished feed, and recent data suggest that the functions of the gastrointestinal tract (GIT) in poultry species might be compromised at doses ranging from 10 to 20 mg/kg, close to field incidences and below the US and EU guidelines. Strategies are therefore necessary to reduce the exposure of poultry to FB. In the present study, we assessed the efficacy of fumonisin esterase FumD (EC 3.1.1.87, commercial name FUMzyme®) to cleave the tricarballylic acid side chains of FB, leading to the formation of non-toxic hydrolyzed fumonisins in the GIT of broiler chickens. Broiler chickens were fed for 14 d (7 to 21 d of age) 3 different diets (6 birds/cage, 6 cages/diet), i) control feed (negative control group), ii) feed contaminated with 10 mg FB/kg (FB group), and iii) feed contaminated with 10 mg FB/kg and supplemented with 100 units of FUMzyme®/kg (FB+FUMzyme® group). To determine the degree of reduction of FB in the GIT, 2 characteristics were analyzed. First, the sphinganine-to-sphingosine ratio in the serum and liver was determined as a biomarker of effect for exposure to FB. Second, the concentration of fumonisin B1 and its hydrolyzed forms was evaluated in the gizzard, the proximal and distal parts of the small intestine, and the excreta. Significantly reduced sphinganine-to-sphingosine ratios in the serum and liver of the FB+FUMzyme® group (serum: 0.15 ± 0.01; liver: 0.17 ± 0.01) compared to the FB group (serum: 0.20 ± 0.01; liver: 0.29 ± 0.03) proved that supplementation of broiler feed with FUMzyme® was effective in partially counteracting the toxic effect of dietary FB. Likewise, FB concentrations in digesta and excreta were significantly reduced in the FB+FUMzyme® group compared to the FB group (P < 0.05; up to 75%). FUMzyme® furthermore partially counteracted FB-induced up-regulation of cytokine gene expression (IL-8 and IL-10) in the jejunum. The FB group showed significantly higher gene expression of IL-8 and IL-10 compared to the negative control group (IL-8: fold change = 2.9 ± 1.1, P < 0.05; IL-10: fold change = 3.6 ± 1.4, P < 0.05), whereas IL-8 and IL-10 mRNA levels were not significantly different in the FB+FUMzyme®® group compared to the other 2 groups. In conclusion, FUMzyme® is suitable to detoxify FB in chickens and maintain gut functions.
| S-EPMC5850661 | biostudies-literature
Project description:Deoxynivalenol (DON) and fumonisins (FB) are the most frequently encountered mycotoxins produced by Fusarium species in livestock diets. The effect of subclinical doses of mycotoxins in chickens is largely unknown, and in particular the susceptibility of birds to pathogenic challenge when fed these fungal metabolites. Therefore, the present study reports the effects of DON and FB on chickens challenged with Eimeria spp, responsible for coccidiosis. Broilers were fed diets from hatch to day 20, containing no mycotoxins, 1.5 mg DON/kg, 20 mg FB/kg, or both toxins (12 pens/diet; 7 birds/pen). At day 14, six pens of birds per diet (half of the birds) were challenged with a 25×-recommended dose of coccidial vaccine, and all birds (challenged and unchallenged) were sampled 6 days later. As expected, performance of birds was strongly affected by the coccidial challenge. Ingestion of mycotoxins did not further affect the growth but repartitioned the rate of reduction (between the fraction due to the change in maintenance and feed efficiency), and reduced apparent nitrogen digestibility. Intestinal lesions and number of oocysts in the jejunal mucosa and feces of challenged birds were more frequent and intense in the birds fed mycotoxins than in birds fed control feed. The upregulation of cytokines (interleukin (IL) IL-1?, IL-6, IL-8 and IL-10) following coccidial infection was higher in the jejunum of birds fed mycotoxins. Further, the higher intestinal immune response was associated with a higher percentage of T lymphocytes CD4?CD25?, also called Tregs, observed in the cecal tonsils of challenged birds fed mycotoxins. Interestingly, the increase in FB biomarker of exposure (sphinganine/sphingosine ratio in serum and liver) suggested a higher absorption and bioavailability of FB in challenged birds. The interaction of DON and FB was very dependent on the endpoint assessed, with three endpoints reporting antagonism, nine additivity, and two synergism. In conclusion, subclinical doses of DON and FB showed little effects in unchallenged chickens, but seem to result in metabolic and immunologic disturbances that amplify the severity of coccidiosis.
| S-EPMC4999847 | biostudies-literature
Project description:Fumonisins are mycotoxins that cause diseases of plants and, when consumed by animals, can damage liver, kidney, lung, brain, and other organs, alter immune function, and cause developmental defects and cancer. They structurally resemble sphingolipids (SLs), and studies nearly 30 years ago discovered that the most prevalent fumonisin [fumonisin B1 (FB1)] potently inhibits ceramide synthases (CerSs), enzymes that use fatty acyl-CoAs to N-acylate sphinganine (Sa), sphingosine (So), and other sphingoid bases. CerS inhibition by FB1 triggers a "perfect storm" of perturbations in structural and signaling SLs that include: reduced formation of dihydroceramides, ceramides, and complex SLs; elevated Sa and So and their 1-phosphates, novel 1-deoxy-sphingoid bases; and alteration of additional lipid metabolites from interrelated pathways. Moreover, because the initial enzyme of sphingoid base biosynthesis remains active (sometimes with increased activity), the impact is multiplied by the continued production of damaging metabolites. Evidence from many studies, including characterization of knockout mice for specific CerSs and analyses of human blood (which found that FB1 intake is associated with elevated Sa 1-phosphate), has consistently pointed to CerS as the proximate target of FB1 It is also apparent that the changes in multiple bioactive lipids and related biologic processes account for the ensuing spectrum of animal and plant disease. Thus, the diseases caused by fumonisins can be categorized as "sphingolipidoses" (in these cases, due to defective SL biosynthesis), and the lessons learned about the consequences of CerS inhibition should be borne in mind when contemplating other naturally occurring and synthetic compounds (and genetic manipulations) that interfere with SL metabolism.
| S-EPMC6602133 | biostudies-literature
Project description:BackgroundIn order to study the relations of hepatocellular functions, weight gain and metabolic imbalance caused by low-dose antibiotics (LDA) via epigenetic regulation of gene transcription, 32 weaned piglets were employed as animal models and randomly allocated into two groups with diets supplemented with 0 or LDA (chlorotetracycline and virginiamycin).ResultsDuring the 4 weeks of the experiment, LDA showed a clear growth-promoting effect, which was exemplified by the significantly elevated body weight and average daily gain. Promoter methylome profiling using liquid hybridization capture-based bisulfite sequencing (LHC-BS) indicated that most of the 745 differential methylation regions (DMRs) were hypermethylated in the LDA group. Several DMRs were significantly enriched in genes related with fatty acids metabolic pathways, such as FABP1 and PCK1. In addition, 71 differentially expressed genes (DEGs) were obtained by strand-specific transcriptome analysis of liver tissues, including ALOX15, CXCL10 and NNMT, which are three key DEGs that function in lipid metabolism and immunity and which had highly elevated expression in the LDA group. In accordance with these molecular changes, the lipidome analyses of serum by LC-MS identified 38 significantly differential lipids, most of which were downregulated in the LDA group.ConclusionsOur results indicate that LDA could induce epigenetic and transcriptional changes of key genes and lead to enhanced efficiency of lipid metabolism in the liver.
| S-EPMC7507292 | biostudies-literature
Project description:Apolipoprotein L1 (APOL1) wild type (G0) plays a role in the metabolism of sphingolipids, glycosphingolipids, sphingomyelin and ceramide, which constitute bioactive components of the lipid rafts (DRM). We asked whether APOL1 variants (APOL1-Vs) G1 and G2 carry the potential to alter the metabolism of sphingolipids in human podocytes. The sphingolipid pattern in HPs overexpressing either APOL1G0 or APOL1-Vs was analysed by using a thin mono- and bi-dimensional layer chromatography, mass-spectrometry and metabolic labelling with [1-3H]sphingosine. HP G0 and G1/G2-Vs exhibit a comparable decrease in lactosylceramide and an increase in the globotriaosylceramide content. An analysis of the main glycohydrolases activity involved in glycosphingolipid catabolism showed an overall decrease in the activeness of the tested enzymes, irrespective of the type of APOL1-Vs expression. Similarly, the high throughput cell live-based assay showed a comparable increased action of the plasma membrane glycosphingolipid-glycohydrolases in living cells independent of the genetic APOL1 expression profile. Importantly, the most significative modification of the sphingolipid pattern induced by APOL1-Vs occurred in DRM resulted with a drastic reduction of radioactivity associated with sphingolipids. G1/G2-Vs present a decrease amount of globotriaosylceramide and globopentaosylceramide compared to G0. Additionally, ceramide at the DRM site and lactosylceramide in general, showed a greatest fall in G1/G2 in comparison with G0. Additionally, the levels of glucosylceramide decreased only in the DRM of human podocytes overexpressing G1/G2-Vs. These findings suggest that altered sphingolipidsprofiles may contribute to the deranged functionality of the plasma membrane in APOL1 risk milieu.
| S-EPMC7679335 | biostudies-literature
Project description:Toxic effects among fumonisins B (FB), deoxynivalenol (DON) and zearalenone (ZEN) administered alone and combined were investigated in 84-day-old ducks during force-feeding. 75 male ducks, divided into five groups of 15 animals, received daily during the meal a capsule containing the desired among of toxin. Treated animals received dietary levels of toxins equivalent to 20 mg FB1+FB2/kg (FB), 5 mg DON/kg (DON), 0.5 mg ZEN/kg (ZEN) and 20, 5 and 0.5 mg/kg of FB, DON and ZEN (FBDONZEN), respectively. Control birds received capsules with no toxin. After 12 days, a decrease in body weight gain accompanied by an increase in the feed conversion ratio was observed in ducks exposed to FBDONZEN, whereas there was no effect on performances in ducks exposed to FB, DON and ZEN separately. No difference among groups was observed in relative organ weight, biochemistry, histopathology and several variables used to measure oxidative damage and testicular function. A sphinganine to sphingosine ratio of 0.32, 1.19 and 1.04, was measured in liver in controls and in ducks exposed to FB and FBDONZEN, respectively. Concentrations of FB1 in liver were 13.34 and 15.4 ng/g in ducks exposed to FB and FBDONZEN, respectively. Together ZEN and its metabolites were measured after enzymatic hydrolysis of the conjugated forms. Mean concentrations of α-zearalenol in liver were 0.82 and 0.54 ng/g in ducks exposed to ZEN and FBDONZEN, respectively. β-zearalenol was 2.3-fold less abundant than α-zearalenol, whereas ZEN was only found in trace amounts. In conclusion, this study suggests that decreased performance may occur in ducks exposed to a combination of FB, DON and ZEN, but does not reveal any other interaction between mycotoxins in any of the other variables measured.
| S-EPMC7920068 | biostudies-literature
Project description:ObjectivesLittle is known about the effect of diet on the oral microbiota of infants, although diet is known to affect the gut microbiota. The aims of the present study were to compare the oral microbiota in breast-fed and formula-fed infants, and investigate growth inhibition of streptococci by infant-isolated lactobacilli.MethodsA total of 207 mothers consented to participation of their 3-month-old infants. A total of 146 (70.5%) infants were exclusively and 38 (18.4%) partially breast-fed, and 23 (11.1%) were exclusively formula-fed. Saliva from all of their infants was cultured for Lactobacillus species, with isolate identifications from 21 infants. Lactobacillus isolates were tested for their ability to suppress Streptococcus mutans and S sanguinis. Oral swabs from 73 infants were analysed by the Human Oral Microbe Identification Microarray (HOMIM) and by quantitative polymerase chain reaction for Lactobacillus gasseri.ResultsLactobacilli were cultured from 27.8% of exclusively and partially breast-fed infants, but not from formula-fed infants. The prevalence of 14 HOMIM-detected taxa, and total salivary lactobacilli counts differed by feeding method. Multivariate modelling of HOMIM-detected bacteria and possible confounders clustered samples from breast-fed infants separately from formula-fed infants. The microbiota of breast-fed infants differed based on vaginal or C-section delivery. Isolates of L plantarum, L gasseri, and L vaginalis inhibited growth of the cariogenic S mutans and the commensal S sanguinis: L plantarum >L gasseri >L vaginalis.ConclusionsThe microbiota of the mouth differs between 3-month-old breast-fed and formula-fed infants. Possible mechanisms for microbial differences observed include species suppression by lactobacilli indigenous to breast milk.
| S-EPMC3548038 | biostudies-literature
Project description:Most herbal polyphenols and flavonoids reveals multiple ameliorative benefits for obesity caused by chronic metabolic disorders. Accumulated studies have revealed that preferable therapeutic effects can be obtained through clinical combination of these two kinds of natural compounds for obesity improvement. The typical representative research was the combination of quercetin and resveratrol (CQR), in which the ratio of quercetin and resveratrol is 2:1, demonstrating a synergistic effect in anti-obesity process. Although there exists reports clarifying the mechanism of the combination of two to improve obesity from the perspective of improving adipose tissue inflammation or modulating the composition of intestinal flora, there are few further studies on the mechanism of drug action from the perspective of metabolites transformation. In this research, we mainly focused on the alterations of endogenous metabolites in rats, and analyzed the urine metabolites of obese and intervention model. Therefore, a gas chromatography-mass spectrometry (GC-MS) based metabolomics approach was applied to assess the potential effects and mechanisms of CQR at different dosages (45, 90, and 180 mg/kg) in high fat diet (HFD)-induced obesity rats. Body weight gain and visceral fat weight were reduced by CQR, as well as blood lipid and inflammatory factor levels were increased by CQR in a dose-related manner. Urinary metabolomics revealed 22 differential metabolites related to the HFD-induced obesity, which were reversed in a dose-dependent manner by CQR, of which 8 were reversed in the 45 mg/kg CQR group, 15 were reversed in the 90 mg/kg CQR group, and 18 were reversed in the 180 mg/kg CQR group. Combined with bioinformatics and pattern recognition, the results demonstrated that the key differential metabolites were basically involved in amino acid metabolism, galactose metabolism, pantothenate and CoA biosynthesis, pyruvate metabolism and lysine degradation. In summary, our results showed significant therapeutic action by CQR administration and remarkable metabolomic changes after HFD feeding and CQR intervention. Urinary metabolomic analysis was highlighted on account of providing holistic and comprehensive insights into the pathophysiological mechanisms of the HFD-induced obesity, which also supplied clues for the future mechanism studies of CQR's anti-obesity effects.
| S-EPMC8085560 | biostudies-literature
Project description:Based on the gut-liver axis theory, to survey the effect of low-dose antibiotic (LDA) to hepatocellular functions of weight gain and metabolic imbalance by epigenetic transcription regulation, 32 weaned piglets were employed as the animal models and half were treated with Chlorotetracycline and Virginiamycin for four weeks. During the experiment, LDA showed an obviously growth-promoting effect, which was exemplified by the significantly elevated body weight and average daily gain. The DNA methylome profiling of promoter using liquid hybridization capture-based bisulfite sequencing (LHC-BS) indicated most of 745 differential methylation regions (DMRs) were hypermethylated in the LDA group, and some other DMRs were significantly enriched in genes related with fatty acids metabolic pathways, such as FABP1 and PCK1. Meanwhile, three key DEGs with the function of lipid metabolism and immunity were obtained by the liver strand-specific transcriptome analysis, including ALOX15, CXCL10 and NNMT, which were highly elevated for expressions in the LDA group. Correspondingly, the lipidome analyses of serum by LC-MS identified 38 significantly differential lipids, most of which were down-regulated in the LDA group. All these results suggest antibiotics could induce epigenetic and transcriptional changes of key genes related lipid metabolism pathway, and contributed to a more efficient metabolism of lipids.
2019-10-31 | GSE122027 | GEO