Anti-Inflammatory Potential of Cow, Donkey and Goat Milk Extracellular Vesicles as Revealed by Metabolomic Profile
<p>Workflow illustration and related scheme of results placement. (<b>a</b>) milk collection, milk extracellular vesicles (MEVs) isolation and characterization; (<b>b</b>) Metabolite extraction and statistical analysis; (<b>b<sub>1</sub></b>) differentially abundant metabolites in P2 compared to the other pools; (<b>b<sub>2</sub></b>) total metabolite content of MEVs in whole P2; (<b>c</b>) network analysis of enriched MEV metabolites; (<b>d</b>) pathway enrichment of entire MEV metabolites content. * EDTA: ethylenediaminetetraacetic acid tetrasodium salt dihydrate.</p> "> Figure 2
<p>(<b>A</b>) Total amount of proteins in the pools of the gradient fractions from cow, goat and donkey milk. Data from representative experiments are reported. (<b>B</b>) Detection of the EV markers in the sucrose gradient pools of fractions. The indicated pools were immunoblotted with TSG101 (upper panels), CD81 (middle panels) and calnexin (lower panels). Each sample contained 30 μg proteins except for the donkey samples that contained 10 μg. The P1 and P5 pools from donkey milk were not tested because the total protein content was not sufficient. Positive controls were: Jurkat cells for CD81 and calnexin (CLX); cow MEVs isolated in previous experiments for TSG101. For each species at least two different preparations were tested; representative images are reported in the panels.</p> "> Figure 3
<p>Electron micrograph showing MEVs isolated from donkey (<b>A</b>), bovine (<b>B</b>) and goat (<b>C</b>) milk. MEVs are round in shape and measure between 30 and 500 nm. Transmission electron microscopy (TEM), scale bar = 500 nm (<b>A</b>,<b>B</b>), 200 nm (<b>C</b>).</p> "> Figure 4
<p>Metabolites enriched in the Bovine P2 fraction. For each fraction, four samples were analyzed. Raw data (quantitative relative ion count) were normalized using the Pareto Scaling normalization and analyzed using the ANOVA test. Only metabolites enriched in the Bovine P2 fraction are reported (FDR <span class="html-italic">p</span> < 0.05). The normalized concentration is reported for each metabolite in the P1, P2, P3, P4, P5 pools. The distribution of the samples is represented by a boxplot. The solid line represents the median, the box reports the interquartile range and the whiskers reports the minimum and maximum value of the distribution. Each sample is represented by a grey point, outliers are reported using a black point.</p> "> Figure 5
<p>Metabolites enriched in the Donkey P2 fraction. For each fraction, four samples were analyzed. Raw data (quantitative relative ion count) were normalized using the Pareto Scaling normalization and analyzed using the ANOVA test. Only metabolites enriched in the Bovine P2 fraction are reported (FDR <span class="html-italic">p</span> < 0.05). The normalized concentration is reported for each metabolite in the P1, P2, P3, P4, P5 pools. The distribution of the samples is represented by a boxplot. The distribution of the samples is represented by a boxplot. The solid line represents the median, the box reports the interquartile range and the whiskers reports the minimum and maximum value of the distribution. Each sample is represented by a grey point, outliers are reported using a black point.</p> "> Figure 6
<p>Metabolites enriched in the Goat P2 pool. For each fraction, four samples were analyzed. Raw data (quantitative relative ion count) were normalized using the Pareto Scaling normalization and analyzed using the ANOVA test. Only metabolites enriched in the Bovine P2 fraction are reported (FDR <span class="html-italic">p</span> < 0.05). The normalized concentration is reported for each metabolite in the P1, P2, P3, P4, P5 pools. The solid line represents the median, the box reports the interquartile range and the whiskers reports the minimum and maximum value of the distribution. Each sample is represented by a grey point, outliers are reported using a black point.</p> "> Figure 7
<p>Visual representation generated by MetScape (CREGN) application of the Urea cycle and metabolism of arginine, proline, glutamate, aspartate and asparagine, a common pathway among the three species. Red hexagons symbolize these input MEV metabolites, arrows indicate their connections with other intermediate compounds (pink hexagons) and enzymes (green squares), which might regulate the identified metabolites. Purple circles represent genes encoding those enzymes and beige rhombuses the reactions catalyzed by those enzymes. (<b>A</b>) Bovine, (<b>B</b>) Donkey, (<b>C</b>) Goat.</p> "> Figure 8
<p>Metabolite Set Enrichment Analysis (MSEA) overview obtained through MetaboAnalyst by plotting -log of <span class="html-italic">p</span>-values from pathway enrichment analysis on the <span class="html-italic">y</span>-axis and pathway impact values from pathway topology analysis on the <span class="html-italic">x</span>-axis. Color intensity (light yellow to red) reflects increasing statistical significance.</p> ">
Abstract
:1. Introduction
2. Materials and Methods
2.1. Milk Collection
2.2. EVs Isolation
2.3. MEVs Characterization
2.3.1. Western Blotting
2.3.2. Transmission Electron Microscopy (TEM)
2.4. Metabolomic Analysis
2.4.1. Metabolite Extraction
2.4.2. UHPLC-HRMS
2.5. Data Elaboration and Statistical Analysis
3. Results
3.1. MEVs Characterization
3.1.1. Western Blotting
3.1.2. Transmission Electron Microscopy
3.2. Metabolomic Analysis
3.3. Network and Pathway Enrichment Analysis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Pathways | Pathway Recurrence among Species | Bovine Metabolites | Donkey Metabolites | Goat Metabolites |
---|---|---|---|---|
Purine metabolism | 3 | Adenine Adenosine; Deoxyinosine; GMP; IMP; Inosine; Guanosine | Adenosine; AMP; dGMP; IMP; Xanthosine | Adenosine; AMP; Deoxyinosine; dGMP; Guanine; Xanthosine |
Pyrimidine metabolism | 3 | Cytidine | dUTP Orotate | dTMP; dUMP; Uridine |
Urea cycle and metabolism of arginine, proline, glutamate, aspartate and asparagine | 3 | Lysine | Glutathione; Glutathione disulfide; Asparagine | S-methyl-5-thioadenosine; Glutathione disulfide; Arginine |
Vitamin B3 (nicotinate and nicotinamide) metabolism | 3 | NAD; NADH; NADP; Nicotinamide ribotide | NAD; Nicotinamide ribotide | Arginine; NAD; NADH |
Methionine and cysteine metabolism | 2 | S-Adenosyl-L-homocysteine | Methionine | |
Tyrosine metabolism | 2 | Diiodothyronine | Diiodothyronine; Phenylalanine; Tyrosine | |
Pentose phosphate pathway | 1 | 2-Dehydro-D-gluconate | ||
Biopterin metabolism | 1 | Phenylalanine; Tyrosine | ||
Galactose metabolism | 1 | Glucose-1-phosphate | ||
Glycerophospholipid metabolism | 1 | Choline | ||
Glycine, serine, alanine and threonine metabolism | 1 | Choline; Arginine; Methionine | ||
Glycolysis and Gluconeogenesis | 1 | Glucose-1-phosphate | ||
Tryptophan metabolism | 1 | Tryptophan | ||
Vitamin B9 (folate) metabolism | 1 | 5-methyl-THF | ||
Vitamin B2 (riboflavin) metabolism | 1 | FMN | ||
Vitamin B6 (pyridoxine) metabolism | 1 | Pyridoxamine | ||
Vitamin H (biotin) metabolism | 1 | Lysine | ||
Lipoate metabolism | 1 | Lysine | ||
Lysine metabolism | 1 | Lysine | ||
None 1 | Allantoin; Cytosine | Acetyllysine; Cytosine; Deoxyribose-phosphate Glucose-6-phosphate Indoleacrylic acid | ||
No KEGG ID 2 | Methionine sulfoxide; 5-deoxyribose-1-phosphate; N(alpha)-Acetyllysine |
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Mecocci, S.; Gevi, F.; Pietrucci, D.; Cavinato, L.; Luly, F.R.; Pascucci, L.; Petrini, S.; Ascenzioni, F.; Zolla, L.; Chillemi, G.; et al. Anti-Inflammatory Potential of Cow, Donkey and Goat Milk Extracellular Vesicles as Revealed by Metabolomic Profile. Nutrients 2020, 12, 2908. https://doi.org/10.3390/nu12102908
Mecocci S, Gevi F, Pietrucci D, Cavinato L, Luly FR, Pascucci L, Petrini S, Ascenzioni F, Zolla L, Chillemi G, et al. Anti-Inflammatory Potential of Cow, Donkey and Goat Milk Extracellular Vesicles as Revealed by Metabolomic Profile. Nutrients. 2020; 12(10):2908. https://doi.org/10.3390/nu12102908
Chicago/Turabian StyleMecocci, Samanta, Federica Gevi, Daniele Pietrucci, Luca Cavinato, Francesco R. Luly, Luisa Pascucci, Stefano Petrini, Fiorentina Ascenzioni, Lello Zolla, Giovanni Chillemi, and et al. 2020. "Anti-Inflammatory Potential of Cow, Donkey and Goat Milk Extracellular Vesicles as Revealed by Metabolomic Profile" Nutrients 12, no. 10: 2908. https://doi.org/10.3390/nu12102908