A Diet Supplemented with Polyphenols, Prebiotics and Omega-3 Fatty Acids Modulates the Intestinal Microbiota and Improves the Profile of Metabolites Linked with Anxiety in Dogs
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Foods
2.2. Animals and Experimental Design
2.3. Sample Collection, Scoring, Processing, and Metabolite Analysis
2.4. Microbiota and Bioinfomatics Processing
2.5. Statistical Analysis
3. Results
3.1. Food, Study Design, and Animals
3.2. Effect of the Study Foods on Blood Chemistry and Plasma Metabolites
3.3. Effect of the Study Foods on Fecal Metabolites
3.4. Effect of the Study Foods on Fecal Microbiota
3.5. Correlations of 4-Ethylphenyl Sulfate with Plasma and Fecal Metabolites and OTUs
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Analyte (%) | Washout Food | Control Food | Test Food |
---|---|---|---|
Ash | 4.3 | 5.5 | 5.4 |
Crude fat | 13.4 | 13.6 | 13.9 |
DHA | <0.01 | 0.08 | 0.06 |
EPA | <0.01 | 0.1 | 0.09 |
DPA | <0.01 | 0.02 | 0.02 |
Omega-3 sum | 0.42 | 0.82 | 0.74 |
Omega-6 sum | 3.9 | 3.3 | 3.3 |
Crude fiber | 1.6 | 1.0 | 1.0 |
Neutral detergent fiber | 7.5 | 3.6 | 3.4 |
Crude protein | 18.8 | 21.5 | 21.4 |
Moisture | 8.1 | 8.1 | 9.0 |
Apparent dry matter digestibility | 84.4 | 87.5 | 84.8 |
True protein digestibility | 87.4 | 92.2 | 91.1 |
Washout Food | Control Food | Test Food | |
---|---|---|---|
Food intake, g | 163.7 ± 0.8 | 170.7 ± 1.3 * | 166.1 ± 1.0 *† |
Body weight, kg | 10.4 ± 2.1 | 10.3 ± 2.0 | 10.3 ± 2.1 |
pH | 5.8 ± 0.04 | 5.8 ± 0.04 | 5.8 ± 0.03 |
Ash, % | 6.5 ± 0.24 | 6.9 ± 0.22 | 6.8 ± 0.18 |
Moisture, % | 70.6 ± 0.48 | 72.4 ± 0.41 * | 71.9 ± 0.34 * |
Ammonia, mmol/g | 0.040 ± 0.001 | 0.035 ± 0.002 * | 0.030 ± 0.001 * |
Stool score | 4.6 ± 0.5 | 4.3 ± 0.6 | 4.4 ± 0.7 |
Colony Reference Range | Washout Food | Control Food | Test Food | |
---|---|---|---|---|
Albumin, g/dL | 2.9–4.0 | 3.4 ± 0.04 | 3.6 ± 0.06 * | 3.6 ± 0.06 * |
BUN, mg/dL | 6.4–20.5 | 11.2 ± 0.50 | 12.8 ± 0.81 * | 12.2 ± 0.77 * |
Creatinine, mg/dL | 0.41–0.82 | 0.68 ± 0.02 | 0.67 ± 0.02 | 0.65 ± 0.02 |
Cholesterol, mg/dL | 133–401 | 196 ± 5.0 | 215 ± 7.5 * | 219 ± 7.7 * |
Sodium, mmol/L | 144–150 | 149 ± 0.19 | 149 ± 0.26 | 149 ± 0.26 |
Triglycerides, mg/dL | 34–429 | 103 ± 8.3 | 97.9 ± 7.7 | 92.7 ± 8.6 |
Calcium, mg/dL | 9.6–11.7 | 10.1 ± 0.06 | 10.2 ± 0.07 * | 10.3 ± 0.08 * |
Chloride, mmol/L | 105–115 | 111 ± 0.27 | 111 ± 0.34 | 110 ± 0.30 * |
Potassium, mmol/L | 4.0–5.3 | 4.7 ± 0.03 | 4.6 ± 0.05 * | 4.6 ± 0.06 * |
Plasma Metabolite | Washout Food | Control Food | Test Food | p Value, Washout vs. Control Food | p Value, Washout vs. Test Food | p Value, Control vs. Test Food |
---|---|---|---|---|---|---|
4-ethylphenyl sulfate (4-EPS) | 0.33 ± 0.07 | −0.29 ± 0.07 | −0.39 ± 0.07 | <0.001 | <0.001 | 0.028 |
DHA; 22:6n3 | −0.4 ± 0.07 | 0.43 ± 0.05 | 0.37 ± 0.06 | <0.001 | <0.001 | NS |
glutamate | 0.09 ± 0.04 | −0.01 ± 0.05 | −0.02 ± 0.04 | 0.001 | <0.001 | NS |
glutamine | 0.04 ± 0.01 | −0.03 ± 0.02 | −0.04 ± 0.01 | <0.001 | <0.001 | NS |
gamma-glutamylglutamate | −0.53 ± 0.13 | −0.74 ± 0.12 | −0.92 ± 0.11 | NS | 0.002 | NS |
dimethylarginine (ADMA + SDMA) | 0.05 ± 0.02 | −0.02 ± 0.02 | −0.02 ± 0.02 | <0.001 | <0.001 | NS |
1-methylnicotinamide | −0.16 ± 0.06 | 0.08 ± 0.04 | 0.08 ± 0.06 | <0.001 | <0.001 | NS |
2-aminobutyrate | −0.08 ± 0.02 | 0.05 ± 0.03 | 0.09 ± 0.03 | <0.001 | <0.001 | NS |
lactate | 0.10 ± 0.04 | −0.03 ± 0.04 | −0.07 ± 0.03 | <0.001 | <0.001 | NS |
choline | 0.09 ± 0.02 | −0.07 ± 0.03 | −0.07 ± 0.03 | <0.001 | <0.001 | NS |
sphingomyelin (d18:2/23:1) | −0.19 ± 0.07 | 0.13 ± 0.06 | 0.05 ± 0.06 | <0.001 | <0.001 | 0.021 |
sphingomyelin (d18:1/24:1, d18:2/24:0) | −0.13 ± 0.05 | 0.17 ± 0.05 | 0.12 ± 0.05 | <0.001 | <0.001 | NS |
citrate | 0.02 ± 0.02 | −0.02 ± 0.02 | −0.02 ± 0.02 | 0.009 | 0.019 | NS |
carboxyethyl-GABA | 0.04 ± 0.08 | −0.002 ± 0.08 | −0.10 ± 0.07 | NS | 0.049 | NS |
hippurate | −0.31 ± 0.15 | −0.20 ± 0.15 | 0.05 ± 0.15 | NS | 0.020 | NS |
indolelactate | −0.08 ± 0.08 | 0.07 ± 0.08 | 0.07 ± 0.07 | 0.033 | NS | NS |
kynurenate | −0.07 ± 0.09 | 0.02 ± 0.08 | −0.02 ± 0.08 | NS | NS | NS |
kynurenine | −0.02 ± 0.05 | −0.06 ± 0.05 | −0.11 ± 0.05 | NS | 0.002 | NS |
N-acetylkynurenine | −0.16 ± 0.10 | 0.04 ± 0.08 | 0.01 ± 0.10 | 0.010 | NS | NS |
phenol sulfate | 0.10 ± 0.11 | 0.02 ± 0.09 | −0.18 ± 0.09 | NS | 0.003 | NS |
serotonin | −0.73 ± 0.18 | −0.35 ± 0.20 | −0.33 ± 0.20 | 0.031 | NS | NS |
azelate (nonanedioate; C9) | 0.05 ± 0.05 | 0.01 ± 0.07 | 0.16 ± 0.07 | NS | NS | NS |
trimethylamine N-oxide | −0.16 ± 0.09 | −0.05 ± 0.09 | 0.05 ± 0.08 | NS | 0.009 | NS |
Fecal Metabolite | Washout Food | Control Food | Test Food | p Value, Washout vs. Control Food | p Value, Washout vs. Test Food | p Value, Control vs. Test Food |
---|---|---|---|---|---|---|
DHA; 22:6n3 | −0.54 ± 0.13 | 0.43 ± 0.10 | 0.37 ± 0.12 | <0.001 | <0.001 | NS |
glutamate | 0.11 ± 0.08 | −0.28 ± 0.10 | −0.32 ± 0.08 | <0.001 | <0.001 | NS |
glutamine | 0.09 ± 0.07 | −0.22 ± 0.08 | −0.43 ± 0.10 | 0.001 | <0.001 | NS |
dimethylarginine (ADMA + SDMA) | −0.01 ± 0.06 | 0.08 ± 0.06 | 0.10 ± 0.05 | 0.048 | 0.003 | NS |
carboxyethyl-GABA | −0.10 ± 0.05 | 0.03 ± 0.04 | 0.13 ± 0.04 | 0.009 | <0.001 | NS |
choline | −0.06 ± 0.06 | −0.15 ± 0.05 | −0.03 ± 0.05 | NS | NS | 0.030 |
1-methylnicotinamide | 0.09 ± 0.19 | −0.30 ± 0.21 | −0.04 ± 0.16 | NS | NS | NS |
lactate | 0.39 ± 0.14 | −0.34 ± 0.18 | −0.38 ± 0.17 | 0.001 | 0.001 | NS |
sphingomyelin (d18:1/24:1, d18:2/24:0) | 0.05 ± 0.17 | −0.35 ± 0.18 | −0.27 ± 0.18 | 0.003 | 0.048 | NS |
hippurate | −0.37 ± 0.18 | −0.70 ± 0.19 | −0.84 ± 0.15 | NS | 0.040 | NS |
indolelactate | 0.14 ± 0.23 | −0.26 ± 0.22 | −0.10 ± 0.19 | 0.040 | NS | NS |
kynurenate | 0.56 ± 0.26 | 0.17 ± 0.22 | −0.08 ± 0.22 | NS | 0.010 | NS |
kynurenine | −0.21 ± 0.04 | 0.39 ± 0.07 | 0.50 ± 0.07 | <0.001 | <0.001 | NS |
N-acetylkynurenine | −0.94 ± 0.14 | 0.70 ± 0.15 | 0.85 ± 0.12 | <0.001 | <0.001 | NS |
phenol sulfate | −0.01 ± 0.20 | 0.21 ± 0.22 | −0.04 ± 0.20 | NS | NS | NS |
serotonin | 0.12 ± 0.09 | −0.06 ± 0.07 | −0.19 ± 0.08 | 0.030 | 0.002 | NS |
azelate (nonanedioate; C9) | −0.07 ± 0.06 | −0.13 ± 0.06 | 0.85 ± 0.06 | NS | <0.001 | <0.001 |
trimethylamine N-oxide | −0.14 ± 0.13 | 0.004 ± 0.14 | −0.03 ± 0.13 | NS | NS | NS |
OTU | Washout Food | Control Food | Test Food | p Value, Washout vs. Control Food | p Value, Washout vs. Test Food | p Value, Control vs. Test Food |
---|---|---|---|---|---|---|
361186 Lachnospiraceae Blautia unclassified | 7.34 ± 0.21 | 8.69 ± 0.26 | 8.64 ± 0.26 | <0.001 | <0.001 | NS |
689975 Porphyromonadaceae Parabacteroides | 0.86 ± 0.19 | 2.18 ± 0.15 | 2.06 ± 0.18 | <0.001 | <0.001 | NS |
1030652 Odoribacteraceae Odoribacter | 0.64 ± 0.27 | 2.1 ± 0.33 | 1.8 ± 0.33 | <0.001 | <0.001 | NS |
93469 Mogibacteriaceae Anaerovorax | −2.72 ± 0.05 | −1.73 ± 0.17 | −2.13 ± 0.14 | <0.001 | <0.001 | 0.026 |
1020403 Actinomycetaceae | −2.73 ± 0.06 | −2.23 ± 0.16 | −2.50 ± 0.11 | 0.008 | 0.033 | NS |
195865 Lachnospiraceae | 6.99 ± 0.33 | 5.93 ± 0.31 | 6.24 ± 0.31 | <0.001 | 0.008 | NS |
13805 Veillonellaceae Anaerovibrio | 4.10 ± 0.29 | 3.13 ± 0.22 | 2.69 ± 0.27 | 0.004 | <0.001 | NS |
1016422 Pasteurellaceae Haemophilus parainfluenzae | 0.91 ± 0.27 | 1.7 ± 0.20 | 1.77 ± 0.20 | 0.002 | 0.002 | NS |
1141218 Coriobacteriaceae Eggerthella | −1.35 ± 0.04 | −1.0 ± 0.12 | −1.22 ± 0.80 | 0.009 | NS | NS |
100035 Helicobacteraceae unclassified | −0.31 ± 0.17 | −0.8 ± 0.12 | −0.73 ± 0.12 | 0.034 | NS | NS |
4342860 Gemellaceae unclassified | −0.79 ± 0.21 | −0.04 ± 0.23 | −0.53 ± 0.19 | 0.004 | NS | 0.043 |
112457 Pasteuriaceae | −1.07 ± 0.04 | −0.86 ± 0.11 | −0.95 ± 0.04 | NS | 0.017 | NS |
52166 Veillonellaceae Megasphaera | 6.57 ± 0.22 | 6.03 ± 0.17 | 6.20 ± 0.19 | 0.020 | 0.031 | NS |
15257 Carnobacteriaceae Carnobacterium viridans | −1.71± 0.03 | −1.55 ± 0.06 | −1.62 ± 0.04 | 0.008 | 0.017 | NS |
100212 Veillonellaceae | 4.65 ± 0.29 | 3.66 ± 0.23 | 4.03 ± 0.22 | 0.003 | 0.033 | NS |
37911 Comamonadaceae Mitsuaria chitosanitabida | −0.04 ± 0.27 | 0.05 ± 0.24 | −0.57 ± 0.25 | NS | 0.017 | 0.018 |
104145 Rikenellaceae Blvii28 | −0.53 ± 0.19 | −0.06 ± 0.15 | −0.27 ± 0.17 | 0.036 | NS | NS |
10001 Enterobacteriaceae unclassified | −0.68 ± 0.33 | 0.79 ± 0.43 | 0.51 ± 0.47 | 0.001 | 0.015 | NS |
965048 Neisseriaceae | −0.48 ± 0.21 | −1.05 ± 0.19 | −0.83 ± 0.25 | 0.004 | NS | NS |
945478 unclassified * | 1.19 ± 0.27 | 1.19 ± 0.24 | 0.74 ± 0.26 | NS | 0.040 | 0.027 |
1090029 Sanguibacteraceae Sanguibacter | −1.30 ± 0.03 | −1.10 ± 0.06 | −1.21 ± 0.04 | 0.001 | 0.007 | NS |
351494 Glycomycetaceae Glycomyces harbinensis | −2.68 ± 0.09 | −2.51 ± 0.11 | −2.37 ± 0.18 | 0.008 | 0.035 | NS |
804742 Euzebyaceae Euzebya | −0.06 ± 0.22 | −0.55 ± 0.16 | −0.64 ± 0.16 | 0.022 | 0.016 | NS |
897625 Coxiellaceae | −1.18 ± 0.04 | −1.09 ± 0.05 | −0.68 ± 0.15 | 0.011 | 0.002 | 0.012 |
1000602 unclassified | −2.4 ± 0.08 | −2.04 ± 0.15 | −2.16 ± 0.12 | 0.040 | NS | NS |
103388 Acholeplasmataceae Acholeplasma | −1.84 ± 0.13 | −1.94 ± 0.06 | −1.55 ± 0.21 | NS | NS | 0.046 |
4361046 Campylobacteraceae Campylobacter unclassified | −0.77 ± 0.25 | 0.64 ± 0.40 | 1.10 ± 0.43 | <0.001 | <0.001 | NS |
1141335 Helicobacteraceae Flexispira unclassified | 0.11 ± 0.23 | 0.19 ± 0.20 | −0.29 ± 0.21 | NS | NS | 0.041 |
10196 Enterobacteriaceae Brenneria | −3.24 ± 0.08 | −2.70 ± 0.15 | −2.82 ± 0.15 | 0.001 | 0.009 | NS |
579304 Lactobacillaceae | −2.97 ± 0.05 | −2.73 ± 0.12 | −2.78 ± 0.10 | 0.017 | NS | NS |
146665 Erysipelotrichaceae Eubacterium biforme | 1.65 ± 0.40 | 0.18 ± 0.30 | 1.10 ± 0.35 | <0.001 | NS | 0.009 |
1000161 Pseudomonadaceae unclassified | 1.76 ± 0.35 | −0.43 ± 0.31 | −0.44 ± 0.27 | <0.001 | <0.001 | NS |
Correlations with Plasma Metabolites | Correlations with Fecal Metabolites | |||||
---|---|---|---|---|---|---|
Metabolite | Estimate ± SE | p Value | r2 | Estimate ± SE | p Value | r2 |
DHA; 22:6n3 | −0.37 ± 0.06 | <0.001 | 0.16 | −0.63 ± 0.13 | <0.001 | 0.16 |
gamma-glutamylglutamate | −0.12 ± 0.06 | 0.041 | 0.01 | - | - | - |
dimethylarginine (ADMA + SDMA | - | - | - | −0.20 ± 0.06 | <0.001 | 0.10 |
2-aminobutyrate | −0.62 ± 0.22 | 0.006 | 0.02 | - | - | - |
choline | - | - | - | −0.15 ± 0.06 | 0.008 | 0.06 |
sphingomyelin (d18:1/24:1, d18:2/24:0) | −0.37 ± 0.13 | 0.007 | 0.01 | - | - | - |
azelate (nonanedioate; C9) | - | - | - | −0.25 ± 0.1 | 0.010 | 0.06 |
hippurate | −0.10 ± 0.04 | 0.021 | 0.02 | - | - | - |
indolelactate | 0.37 ± 0.09 | <0.001 | 0.01 | - | - | - |
kynurenine | 0.72 ± 0.14 | <0.001 | 0.15 | −0.35 ± 0.08 | <0.001 | 0.15 |
N-acetylkynurenine | 0.28 ± 0.07 | <0.001 | 0.31 | −1.20 ± 0.17 | <0.001 | 0.31 |
phenol sulfate | 0.35 ± 0.07 | <0.001 | 0.001 | - | - | - |
trimethylamine N-oxide | −0.32 ± 0.08 | <0.001 | 0.004 | - | - | - |
OTU | Estimate | p Value | r2 |
---|---|---|---|
361186 Lachnospiraceae Blautia | −1.03 | <0.001 | 0.12 |
689975 Porphyromonadaceae Parabacteroides | −0.99 | <0.001 | 0.20 |
1030652 Odoribacteraceae Odoribacter | −1.11 | 0.001 | 0.09 |
93469 Mogibacteriaceae Anaerovorax | −0.41 | 0.006 | 0.06 |
1020403 Actinomycetaceae | −0.37 | 0.003 | 0.07 |
1016422 Pasteurellaceae Haemophilus parainfluenzae | −0.79 | 0.001 | 0.09 |
10196f Enterobacteriaceae Brenneria | −0.31 | 0.023 | 0.04 |
4361046 Campylobacteraceae Campylobacter | −1.10 | 0.006 | 0.06 |
109002 Sanguibacteraceae Sanguibacter | −0.13 | 0.009 | 0.06 |
897625 Coxiellaceae | −0.30 | 0.003 | 0.07 |
10001 Enterobacteriaceae unclassified | −1.10 | 0.013 | 0.05 |
1000161 Pseudomonadaceae unclassified | 0.93 | 0.012 | 0.05 |
1141335 Helicobacteraceae Flexispira | 0.67 | 0.002 | 0.08 |
13805 Veillonellaceae Anaerovibrio | 0.83 | 0.004 | 0.07 |
146665 Erysipelotrichaceae Eubacterium biforme | 1.03 | 0.006 | 0.06 |
37911 Comamonadaceae Mitsuaria chitosanitabida | 0.60 | 0.026 | 0.04 |
945478 unclassified * | 0.83 | 0.002 | 0.08 |
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Ephraim, E.; Brockman, J.A.; Jewell, D.E. A Diet Supplemented with Polyphenols, Prebiotics and Omega-3 Fatty Acids Modulates the Intestinal Microbiota and Improves the Profile of Metabolites Linked with Anxiety in Dogs. Biology 2022, 11, 976. https://doi.org/10.3390/biology11070976
Ephraim E, Brockman JA, Jewell DE. A Diet Supplemented with Polyphenols, Prebiotics and Omega-3 Fatty Acids Modulates the Intestinal Microbiota and Improves the Profile of Metabolites Linked with Anxiety in Dogs. Biology. 2022; 11(7):976. https://doi.org/10.3390/biology11070976
Chicago/Turabian StyleEphraim, Eden, Jeffrey A. Brockman, and Dennis E. Jewell. 2022. "A Diet Supplemented with Polyphenols, Prebiotics and Omega-3 Fatty Acids Modulates the Intestinal Microbiota and Improves the Profile of Metabolites Linked with Anxiety in Dogs" Biology 11, no. 7: 976. https://doi.org/10.3390/biology11070976
APA StyleEphraim, E., Brockman, J. A., & Jewell, D. E. (2022). A Diet Supplemented with Polyphenols, Prebiotics and Omega-3 Fatty Acids Modulates the Intestinal Microbiota and Improves the Profile of Metabolites Linked with Anxiety in Dogs. Biology, 11(7), 976. https://doi.org/10.3390/biology11070976