Nonalcoholic Fatty Liver Disease Is Exacerbated in High-Fat Diet-Fed Gnotobiotic Mice by Colonization with the Gut Microbiota from Patients with Nonalcoholic Steatohepatitis
Abstract
1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Microbiota Transplantation and Experimental Design
2.3. Clinical Chemistry
2.4. Histopathological Evaluation
2.5. Oil Red O Staining
2.6. Liver TGs
2.7. Limulus Amebocyte Lysate Test
2.8. Serum Levels of Tnf-α, IL-6, Mcp1, and Insulin
2.9. Quantitative Real-Time Reverse-Transcription PCR (qRT-PCR)
2.10. Gut Bacterial Composition
2.11. Statistical Analysis
3. Results
3.1. Effects of the Gut Microbiota on Body, Liver, and Epididymal Fat Weight in Mice
3.2. Changes in Clinical Biochemistry Parameters as a Result of Colonization by Different Human Gut Microbiota
3.3. Liver of the NASH-HFD Mice Showed a More Advanced Stage of Steatohepatitis
3.4. Serum Levels of Cytokines and Endotoxin Are Significantly Elevated in NASH-HFD Mice
3.5. Analysis of Gene Expression by Real-Time PCR
3.6. Analysis of Gut Microbiota Composition
4. Discussion
5. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Characteristic | p Values for Two-Way ANOVA | ||||||
---|---|---|---|---|---|---|---|
STD | HFD | Main Effect of Microbiota | Main Effect of Diet | Interaction (M × D) | |||
HL | NASH | HL | NASH | ||||
Terminal body weight (g) | 30.7 ± 2.8 | 31.6 ± 2.0 | 48.1 ± 3.0 | 48.6 ± 3.0 | 0.532 | <0.0001 | 0.852 |
Absolute liver weight (g) | 1.4 ± 0.2 | 1.4 ± 0.1 | 2.6 ± 0.3 | 2.4 ± 0.8 | 0.621 | <0.0001 | 0.674 |
Relative liver weight (percent of terminal body weight) | 4.5 ± 0.3 | 4.3 ± 0.2 | 5.2 ± 0.3 | 4.9 ± 1.5 | 0.394 | 0.049 | 0.747 |
Absolute epididymal fat weight (g) | 0.9 ± 0.2 | 1.3 ± 0.2 # | 1.9 ± 0.2 | 2.7 ± 0.5 * | <0.0001 | <0.0001 | 0.077 |
Relative epididymal fat weight (percent of terminal body weight) | 2.8 ± 0.4 | 4.1 ± 0.5 # | 3.9 ± 0.3 | 5.7 ± 1.4 * | <0.0001 | 0.0002 | 0.326 |
P Values for Two-Way ANOVA | |||||||
---|---|---|---|---|---|---|---|
Characteristic | STD | HFD | Main Effect of Microbiota | Main Effect of Diet | Interaction (M × D) | ||
HL | NASH | HL | NASH | ||||
ALT (U/L) | 14.7 ± 2.8 | 53.1 ± 25.5 | 138.3 ± 58.7 | 230.7 ± 83.1 * | 0.009 | <0.0001 | 0.248 |
AST (U/L) | 78.2 ± 14.5 | 161.0 ± 23.9 # | 127.8 ± 30.2 | 218.2 ± 67.0 * | 0.0001 | 0.007 | 0.832 |
Glucose (mmol/L) | 15.6 ± 0.80 | 16.5 ± 0.87 | 15.7 ± 2.46 | 20.7 ± 0.89 * | 0.017 | 0.078 | 0.085 |
T-CHO (mmol/L) | 3.67 ± 0.78 | 3.01 ± 0.8 | 6.22 ± 0.32 | 6.48 ± 0.91 | 0.531 | <0.0001 | 0.146 |
TGs (mmol/L) | 0.63 ± 0.26 | 0.62 ± 0.12 | 0.81 ± 0.21 | 0.98 ± 0.24 | 0.413 | 0.006 | 0.330 |
HDL-C (mmol/L) | 2.96 ± 0.26 | 2.47 ± 0.62 # | 4.05 ± 0.19 | 3.97 ± 0.37 | 0.087 | <0.0001 | 0.218 |
NEFAs (mmol/L) | 0.7 ± 0.2 | 0.7 ± 0.2 | 1.4 ± 0.1 | 1.2 ± 0.2 | 0.373 | <0.0001 | 0.135 |
Insulin (μU/mL) | 74.9 ± 24.1 | 25.4 ± 3.7 # | 171.3 ± 36.1 | 99.9 ± 19.9 * | 0.0001 | <0.0001 | 0.368 |
HOMA-IR | 52.8 ± 9.3 | 18.4 ± 2.7 # | 119.4 ± 28.1 | 88.9 ± 20.6 | 0.0058 | <0.0001 | 0.8473 |
Characteristic | STD | HFD | ||
---|---|---|---|---|
HL | NASH | HL | NASH | |
Streptococcaceae | 7.3 ± 0.3 | 9.1 ± 0.4 | 7.1 ± 0.7 | 9.8 ± 0.1 * |
Lactobacillaceae | 9.1 ± 0.8 | 8.0 ± 0.3 | 9.8 ± 0.2 | 9.5 ± 0.6 |
Eubacteriaceae | 9.8 ± 0.2 | 9.7 ± 0.4 | 9.6 ± 0.3 | 9.9 ± 0.1 |
Clostridiaceae | 9.3 ± 0.1 | 9.2 ± 0.6 | 8.8 ± 0.4 | 9.5 ± 0.2 * |
Bacteroidaceae | 9.6 ± 0.5 | 9.5 ± 0.2 | 9.6 ± 0.6 | 9.8 ± 0.4 |
Enterobacteriaceae | 6.7 ± 0.4 | 7.8 ± 0.8 | 7.2 ± 0.6 | 8.9 ± 0.9 * |
Yeasts | 5.4 ± 0.1 # | 6.6 ± 0.1 * | ||
Total counts | 10.2 ± 0.2 | 10.1 ± 0.2 | 10.2 ± 0.2 | 10.4 ± 0.1 |
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Chiu, C.-C.; Ching, Y.-H.; Li, Y.-P.; Liu, J.-Y.; Huang, Y.-T.; Huang, Y.-W.; Yang, S.-S.; Huang, W.-C.; Chuang, H.-L. Nonalcoholic Fatty Liver Disease Is Exacerbated in High-Fat Diet-Fed Gnotobiotic Mice by Colonization with the Gut Microbiota from Patients with Nonalcoholic Steatohepatitis. Nutrients 2017, 9, 1220. https://doi.org/10.3390/nu9111220
Chiu C-C, Ching Y-H, Li Y-P, Liu J-Y, Huang Y-T, Huang Y-W, Yang S-S, Huang W-C, Chuang H-L. Nonalcoholic Fatty Liver Disease Is Exacerbated in High-Fat Diet-Fed Gnotobiotic Mice by Colonization with the Gut Microbiota from Patients with Nonalcoholic Steatohepatitis. Nutrients. 2017; 9(11):1220. https://doi.org/10.3390/nu9111220
Chicago/Turabian StyleChiu, Chien-Chao, Yung-Hao Ching, Yen-Peng Li, Ju-Yun Liu, Yen-Te Huang, Yi-Wen Huang, Sien-Sing Yang, Wen-Ching Huang, and Hsiao-Li Chuang. 2017. "Nonalcoholic Fatty Liver Disease Is Exacerbated in High-Fat Diet-Fed Gnotobiotic Mice by Colonization with the Gut Microbiota from Patients with Nonalcoholic Steatohepatitis" Nutrients 9, no. 11: 1220. https://doi.org/10.3390/nu9111220
APA StyleChiu, C.-C., Ching, Y.-H., Li, Y.-P., Liu, J.-Y., Huang, Y.-T., Huang, Y.-W., Yang, S.-S., Huang, W.-C., & Chuang, H.-L. (2017). Nonalcoholic Fatty Liver Disease Is Exacerbated in High-Fat Diet-Fed Gnotobiotic Mice by Colonization with the Gut Microbiota from Patients with Nonalcoholic Steatohepatitis. Nutrients, 9(11), 1220. https://doi.org/10.3390/nu9111220