Target Metabolites to Slow Down Progression of Amyotrophic Lateral Sclerosis in Mice
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Butyrate Treatment in Mice
2.3. Fecal Sample Collection
2.4. Bioinformatic Analysis of Metabolomics Data via Metabolon Platform
2.4.1. Sample Accessioning and Sample Preparation
2.4.2. QA/QC
2.4.3. Data Extraction and Compound Identification
2.4.4. Curation
2.4.5. Metabolite Quantification and Data Normalization
2.4.6. Immunofluorescence
2.4.7. Mouse Cytokines
2.4.8. LPS Detection
2.4.9. Statistical Analysis
3. Results
3.1. Altered Microbial Metabolites in the ALS Mice over Course of Disease
3.1.1. Changes in Carbohydrates in the SOD1G93A Mice
3.1.2. Changes of Amino Acids/Proteins in SOD1G93A Mice
3.1.3. Changes in Lipids in SOD1G93A Mice
3.2. Dietary Butyrate Treatment Altered the Metabolite Profile of ALS Mice over Disease Course
3.2.1. Changes in Carbohydrates in Butyrate-Treated SOD1G93A Mice
3.2.2. Changes in Amino Acids/Proteins in Butyrate-Treated SOD1G93A Mice
3.2.3. Changes in Lipids in Butyrate Treated SOD1G93A Mice
3.3. Neuroactive Metabolites Increase Significantly at Onset in ALS Mice
3.4. Dietary Butyrate Treatment Altered Neuroactive Metabolites in ALS Mice over Disease Course
3.5. Energy-Related Metabolites Are Altered during Onset and Decreased following Butyrate Treatment in ALS Mice
3.6. Gamma-Glutamyl Amino Acid Metabolites Are Altered following Butyrate Treatment in ALS Mice
3.7. Short-Chain Fatty Acids (SCFA) in the WT and ALS Mice with or without Butyrate Treatment
3.8. Butyrate Treatment Reduced Lumbar Spine IBA1 Expression, Serum IL-17, and LPS Expression in SOD1G93A Mice
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Statistical Comparisons | ||||
---|---|---|---|---|
Welch’s Two-Sample t-Test | SOD1G93A/WT | |||
4 Week | 8 Week | 13 Week | 17 Week | |
Total biochemicals p ≤ 0.05 | 61 | 7 | 180 | 10 |
Biochemicals (↑↓) | 49 | 12 | 5 | 2 | 175 | 5 | 6 | 4 |
Statistical Comparisons | |||
---|---|---|---|
Welch’s Two-Sample t-Test | SOD1G93A/WT | ||
Baseline | 3 Week Post Butyrate Treatment | 6 Week Post Butyrate Treatment | |
Total biochemicals p ≤ 0.05 | 74 | 107 | 81 |
Biochemicals (↑↓) | 61 | 13 | 43 | 64 | 32 | 49 |
WT | G93A | |||
---|---|---|---|---|
Biochemical Name | 3 Week Post-Butyrate Treatment /Baseline | 6 Week Post-Butyrate Treatment /Baseline | 3 Week Post-Butyrate Treatment /Baseline | 6 Week Post-Butyrate Treatment /Baseline |
Gamma-glutamylalanine | 1.34 | 0.59 | 0.51 | 0.92 |
Gamma-glutamylglutamate | 0.49 | 0.33 | 0.26 | 0.43 |
Gamma-glutamylglutamine | 0.79 | 0.78 | 0.30 | 0.42 |
Gamma-glutamylglycine | 0.86 | 0.49 | 0.39 | 0.69 |
Gamma-glutamylhistidine | 0.48 | 0.50 | 0.33 | 0.41 |
Gamma-glutamylisoleucine | 0.81 | 0.61 | 0.37 | 0.61 |
Gamma-glutamylleucine | 1.30 | 0.91 | 0.36 | 0.64 |
Gamma-glutamyl-apha-lysine | 0.90 | 0.60 | 0.37 | 0.58 |
Gamma-glutamyl-epsilon-lysine | 1.39 | 1.84 | 0.37 | 0.46 |
Gamma-glutamylmethionine | 1.43 | 1.16 | 0.25 | 0.60 |
Gamma-glutamylphenyalanine | 0.88 | 0.62 | 0.30 | 0.57 |
Gamma-glutamylthreonine | 0.98 | 0.71 | 0.35 | 0.69 |
Gamma-glutamyltryosine | 0.73 | 0.72 | 0.33 | 0.75 |
Gamma-glutamylvaline | 1.20 | 0.74 | 0.32 | 0.59 |
Gamma-glutamylserine | 0.57 | 0.56 | 0.44 | 0.69 |
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Ogbu, D.; Zhang, Y.; Claud, K.; Xia, Y.; Sun, J. Target Metabolites to Slow Down Progression of Amyotrophic Lateral Sclerosis in Mice. Metabolites 2022, 12, 1253. https://doi.org/10.3390/metabo12121253
Ogbu D, Zhang Y, Claud K, Xia Y, Sun J. Target Metabolites to Slow Down Progression of Amyotrophic Lateral Sclerosis in Mice. Metabolites. 2022; 12(12):1253. https://doi.org/10.3390/metabo12121253
Chicago/Turabian StyleOgbu, Destiny, Yongguo Zhang, Katerina Claud, Yinglin Xia, and Jun Sun. 2022. "Target Metabolites to Slow Down Progression of Amyotrophic Lateral Sclerosis in Mice" Metabolites 12, no. 12: 1253. https://doi.org/10.3390/metabo12121253