Diet-Independent Correlations between Bacteria and Dysfunction of Gut, Adipose Tissue, and Liver: A Comprehensive Microbiota Analysis in Feces and Mucosa of the Ileum and Colon in Obese Mice with NAFLD
Abstract
:1. Introduction
2. Results
2.1. All ED Diets Resulted in NAFLD in the Context of Obesity, White Adipose Tissue Dysfunction, and Gut Dysfunction
2.2. Global Analysis of Fecal and Mucosal Microbiota Composition in Colon and Ileum
2.3. Microbiota Composition Associations with NAFLD Disease Endpoints
3. Discussion
4. Materials and Methods
4.1. Animals, Diets, and Study Design
4.2. Blood Chemistry
4.3. Histological Analysis of Adipose Tissue and Liver
4.4. FD4 Gut Permeability Assay
4.5. Statistical Analysis
4.6. Gut Microbiota Analysis
4.6.1. Collection and DNA Isolation
4.6.2. Metagenomic Sequencing and Data Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
NAFLD | Non-alcoholic fatty liver disease |
NASH | Non-alcoholic steatohepatitis |
Ldlr−/− | Low-density lipoprotein receptor knockout |
ED | Energy-dense |
BF | Butter fat fructose |
LS | Lard fat sucrose |
LS+FW | Lard fat sucrose and fructose water |
HFD | High-fat diet |
SCFA | Short-chain fatty acid |
ALT | Alanine-aminotransferase |
TG | Triglycerides |
WAT | White adipose tissue |
CLS | Crown-like structures |
FD4 | Fluorescein isothiocyanate-labeled dextran 4 |
LC-MS | Liquid chromatography–mass spectrometry |
NMDS | Non-metric multidimensional scaling |
CV-score | Cross-validation score |
rCCA | Regularized canonical correlation analysis |
IR | Insulin resistance |
UPLC | Ultraperformance liquid chromatography |
HR-MS | High-resolution mass spectrometry |
References
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Chow | BF | LS | LS+FW | |
---|---|---|---|---|
Body weight (g) | 29.1 ± 2.2 | 34.5 ± 3.8 ** | 37.8 ± 6.0 *** | 40.1 ± 5.1 *** |
Total caloric intake (kcal/day) | 11.0 ± 0.7 | 11.7 ± 1.1 | 11.5 ± 0.5 | 12.6 ± 0.8 |
Total fat mass (g) | 3.7 ± 1.0 | 9.1 ± 1.9 *** | 11.8 ± 4.0 *** | 13.4 ± 4.8 *** |
Plasma cholesterol (mM) | 8.9 ± 1.8 | 50.9 ± 10.9 *** | 20.3 ± 6.2 *** | 24.3 ± 10.8 *** |
Plasma triglycerides (mM) | 1.6 ± 0.4 | 10.3 ± 2.4 *** | 4.9 ± 1.9 *** | 4.5 ± 2.6 *** |
Plasma insulin (ng/mL) | 1.3 ± 0.6 | 4.2 ± 1.2 | 4.6 ± 2.1 * | 8.0 ± 6.8 * |
Blood glucose (mM) | 7.2 ± 1.0 | 6.3 ± 0.9 | 7.6 ± 2.1 | 7.7 ± 1.5 ** |
ALT (U/L) | 32.6 ± 7.3 | 139.7 ± 76.4 *** | 78.9 ± 50.0 | 137.1 ± 99.3 *** |
Chow | BF | LS | LS+FW | |
---|---|---|---|---|
Acetate (nM) | 5966.6 ± 874.1 | 4828.2 ± 891.8 ** | 6468.3 ± 1361.3 | 4977.9 ± 810.9 ** |
Butyrate (nM) | 123.7 ± 67.1 | 55.6 ± 14.4 ** | 142.3 ± 90.7 | 45.8 ± 7.3 ** |
Propionate (nM) | 257.8 ± 103.3 | 310.8 ± 127.1 | 464.6 ± 214.9 ** | 388.3 ± 171.6 |
Isobutyrate (nM) | 33.5 ± 7.3 | 45.7 ± 11.6 | 88.9 ± 42.7 *** | 57.6 ± 12.2 * |
Methylbutyrate (nM) | 36.6 ± 8.5 | 46.9 ± 8.7 | 81.9 ± 34.6 *** | 54.8 ± 8.9 * |
Isovalerate (nM) | 26.9 ± 4.6 | 33.3 ± 7.7 | 66.7 ± 16.7 *** | 60.9 ± 19.8 *** |
Valerate (nM) | 10.8 ± 5.7 | 19.9 ± 11.8 | 36.4 ± 14.4 *** | 23.7 ± 10.2 ** |
Histological and Functional Readouts | Metabolites | ||
---|---|---|---|
Colon | Feces | 0.56 | 0.43 |
Mucosa | 0.71 | 0.62 | |
Ileum | Feces | 0.60 | 0.62 |
Mucosa | 0.52 | 0.41 |
Chow | BF | LS | LS+FW | |
---|---|---|---|---|
Fat | 9% kcal (Cereal grains and soy) | 41% kcal (Butter fat) | 45% kcal (Lard) | Same as LS |
Protein | 24% kcal (Soy and cereal grains) | 14% kcal (Casein) | 20% kcal (Casein) | Same as LS |
Carbohydrate | 67% kcal (Starch) | 44% kcal (Fructose) | 35% kcal (Sucrose) | Same as LS |
Cholesterol | - | - | - | - |
kcal/gram | 3.2 kcal/g | 4.5 kcal/g | 4.7 kcal/g | Same as LS |
Fiber | 4.9% w/w | 5.1% w/w | 5.8% w/w | Same as LS |
Drink | Water | Water | Water | 10% w/v fructose in water |
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Gart, E.; Souto Lima, E.; Schuren, F.; De Ruiter, C.G.F.; Attema, J.; Verschuren, L.; Keijer, J.; Salic, K.; Morrison, M.C.; Kleemann, R. Diet-Independent Correlations between Bacteria and Dysfunction of Gut, Adipose Tissue, and Liver: A Comprehensive Microbiota Analysis in Feces and Mucosa of the Ileum and Colon in Obese Mice with NAFLD. Int. J. Mol. Sci. 2019, 20, 1. https://doi.org/10.3390/ijms20010001
Gart E, Souto Lima E, Schuren F, De Ruiter CGF, Attema J, Verschuren L, Keijer J, Salic K, Morrison MC, Kleemann R. Diet-Independent Correlations between Bacteria and Dysfunction of Gut, Adipose Tissue, and Liver: A Comprehensive Microbiota Analysis in Feces and Mucosa of the Ileum and Colon in Obese Mice with NAFLD. International Journal of Molecular Sciences. 2019; 20(1):1. https://doi.org/10.3390/ijms20010001
Chicago/Turabian StyleGart, Eveline, Everton Souto Lima, Frank Schuren, Christa G. F. De Ruiter, Joline Attema, Lars Verschuren, Jaap Keijer, Kanita Salic, Martine C. Morrison, and Robert Kleemann. 2019. "Diet-Independent Correlations between Bacteria and Dysfunction of Gut, Adipose Tissue, and Liver: A Comprehensive Microbiota Analysis in Feces and Mucosa of the Ileum and Colon in Obese Mice with NAFLD" International Journal of Molecular Sciences 20, no. 1: 1. https://doi.org/10.3390/ijms20010001