Investigating Multi-Omic Signatures of Ethnicity and Dysglycaemia in Asian Chinese and European Caucasian Adults: Cross-Sectional Analysis of the TOFI_Asia Study at 4-Year Follow-Up
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Background
Ethics Approval and Trial Registration
2.2. Sample Collection
2.2.1. Faecal Sample Collection
2.2.2. Anthropometric, Clinical, and Biochemical Assessments
2.3. Sample Analysis
2.3.1. Shotgun Metagenomics
2.3.2. Untargeted Metabolomics
2.4. Data Preprocessing
2.4.1. Clinical and Biochemical Characteristic Preprocessing
2.4.2. Shotgun Metagenomics Sequence Processing
2.4.3. Metabolomics Data Processing
2.5. Bioinformatics and Statistical Analysis
2.5.1. Univariate Analysis of the Multi-Omic Dataset
2.5.2. Integrated Analysis of Clinical, Metagenomic, and Metabolomic Data Using Mixomics
3. Results
3.1. Multi-Omic Signatures of Ethnicity
3.2. Cross-Omic Microbial–Metabolite Hubs in Ethnicity-Stratified Analysis
3.3. Influence of Glycaemic Status on Multi-Omics Datasets
3.4. Assessing Block-Specific Discrimination: Polar Metabolite-Driven Sex Separation
4. Discussion
4.1. Metagenomic Distinctions Are Primarily Driven by Ethnicity and Not Glycaemic Status
4.2. Cross-Omic Correlation Structure Reveals Metabolic and Microbial Hubs
4.3. Metabolomic Datasets Reinforce Ethnicity over Metabolic Status Separation
4.4. Sex-Associated Variation in Polar Metabolite Signatures
4.5. Methodological Considerations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Variable | Asian Chinese (n = 99) | European Caucasian (n = 72) | p-Value | Normo-Glycaemia (n = 130) | Prediabetes (n = 41) | p-Value |
---|---|---|---|---|---|---|
M:F ratio | 40:59 | 30:42 | 0.99 | 43:87 | 27:14 | <0.01 |
Age (y) | 46.6 ± 12.8 | 51.2 ± 15.6 | 0.05 | 46.9 ± 14.2 | 53.8 ± 13.1 | <0.01 |
Body weight (kg) | 73.2 ± 13 | 81.3 ± 16.7 | <0.01 | 75.2 ± 15.6 | 81.1 ± 12.8 | <0.01 |
Height (m) | 1.7 ± 0.1 | 1.7 ± 0.1 | <0.01 | 1.7 ± 0.1 | 1.7 ± 0.1 | 0.27 |
BMI (kg m−2) | 26.7 ± 3.7 | 27.1 ± 4.7 | 0.77 | 26.5 ± 4.4 | 28.1 ± 3.3 | 0.01 |
Waist circumf. (cm) | 89.3 ± 10.4 | 93.2 ± 13.7 | 0.09 | 89.1 ± 11.8 | 96.8 ± 11.1 | <0.01 |
Hip circumf. (cm) | 102.1 ± 6.6 | 107.6 ± 10 | <0.01 | 104.1 ± 8.9 | 105.3 ± 7.6 | 0.42 |
SBP (mm Hg) | 123 ± 17.3 | 117.5 ± 16.7 | 0.02 | 119.1 ± 17.3 | 125.7 ± 16.1 | <0.01 |
DBP (mm Hg) | 70 ± 11.1 | 65.4 ± 8.5 | <0.01 | 67.5 ± 10.2 | 70 ± 10.5 | 0.18 |
TBF (kg) | 24.5 ± 7.2 | 28.1 ± 11.1 | 0.05 | 25.8 ± 9.5 | 26.8 ± 7.8 | 0.39 |
TBF (%) | 34.7 ± 7 | 35.2 ± 9.2 | 0.86 | 35.1 ± 8.2 | 34.3 ± 7.4 | 0.29 |
AAT (kg) | 2.3 ± 0.9 | 2.6 ± 1.4 | 0.15 | 2.3 ± 1.2 | 2.8 ± 1 | <0.01 |
AAT (%) | 40.1 ± 9.2 | 39.8 ± 12.3 | 0.89 | 39.2 ± 11 | 42.4 ± 8.6 | 0.14 |
VAT (kg) | 1.1 ± 0.7 | 1.1 ± 0.9 | 0.87 | 0.9 ± 0.7 | 1.5 ± 0.7 | <0.01 |
VAT (%) | 43.4 ± 17.3 | 38.8 ± 20.4 | 0.08 | 37.2 ± 17.8 | 54.9 ± 14.9 | <0.01 |
SAT (kg) | 1.2 ± 0.5 | 1.5 ± 0.8 | 0.03 | 1.4 ± 0.7 | 1.2 ± 0.6 | 0.11 |
SAT (%) | 56.6 ± 17.3 | 61.2 ± 20.4 | 0.08 | 62.8 ± 17.8 | 45.1 ± 14.9 | <0.01 |
VAT:SAT ratio | 1.0 ± 1.0 | 0.9 ± 1.0 | 0.08 | 0.8 ± 0.8 | 1.6 ± 1.3 | <0.01 |
HbA1c (mmol mol−1) | 36.7 ± 4 | 34.5 ± 3.3 | <0.01 | 35.0 ± 3.6 | 38.3 ± 3.7 | <0.01 |
FPG (mmol L−1) | 5.4 ± 0.5 | 5.2 ± 0.5 | 0.04 | 5.2 ± 0.5 | 5.8 ± 0.4 | <0.01 |
ALT (U L−1) | 23.8 ± 19.9 | 16.5 ± 10.5 | <0.01 | 19.9 ± 16.7 | 23.4 ± 17.7 | 0.03 |
AST (U L−1) | 24.7 ± 12.9 | 21.8 ± 5.1 | 0.58 | 23.4 ± 11.3 | 23.9 ± 7.4 | 0.2 |
ALP (U L−1) | 60.9 ± 14.4 | 59.4 ± 14.6 | 0.56 | 60.1 ± 14.6 | 60.8 ± 14.1 | 0.74 |
GGT (U L−1) | 30.6 ± 24.8 | 27.7 ± 27.1 | 0.26 | 26.5 ± 21.6 | 38.5 ± 34.8 | <0.01 |
Total cholesterol (mmol L−1) | 5.2 ± 1 | 5.3 ± 1.1 | 0.44 | 5.2 ± 1.1 | 5.1 ± 1 | 0.4 |
HDL-C (mmol L−1) | 1.5 ± 0.4 | 1.7 ± 0.5 | 0.05 | 1.6 ± 0.4 | 1.4 ± 0.3 | <0.01 |
TG (mmol L−1) | 1.4 ± 0.9 | 1.1 ± 0.6 | 0.02 | 1.2 ± 0.7 | 1.6 ± 1 | <0.01 |
LDL-C (mmol L−1) | 3 ± 0.8 | 3.1 ± 0.9 | 0.53 | 3.1 ± 0.9 | 3 ± 0.9 | 0.59 |
Amylin (pg mL−1) | 31.2 ± 28.9 | 28.7 ± 17.4 | 0.76 | 28.9 ± 25.6 | 34.3 ± 21.3 | 0.07 |
C-peptide (pg mL−1) | 1206.4 ± 633.7 | 1257.9 ± 555.2 | 0.49 | 1186.5 ± 596.2 | 1359.9 ± 603.3 | 0.02 |
GIP (pg mL−1) | 63.2 ± 34.5 | 59.9 ± 27.7 | 0.84 | 60.4 ± 32.3 | 66.3 ± 29.9 | 0.19 |
GLP-1 (pg mL−1) | 201.6 ± 98.3 | 193.5 ± 78.5 | 0.62 | 191.1 ± 92.4 | 220.7 ± 80.3 | <0.01 |
Glucagon (pg mL−1) | 64.2 ± 31.3 | 57.7 ± 32 | 0.05 | 58.4 ± 31.3 | 71.1 ± 31.2 | <0.01 |
Fasting insulin (pg mL−1) | 758.9 ± 695.3 | 766.4 ± 657.5 | 0.88 | 726 ± 640.4 | 876.3 ± 782.1 | 0.2 |
HOMA2-IR | 2.3 ± 1.6 | 2.3 ± 1.8 | 0.85 | 2.2 ± 1.7 | 2.6 ± 1.8 | 0.13 |
HOMA2-B | 140.9 ± 77.1 | 150.7 ± 83.1 | 0.6 | 148.2 ± 81.9 | 135.1 ± 72 | 0.43 |
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Faraj, S.; Joblin-Mills, A.; Sequeira-Bisson, I.R.; Leiu, K.H.; Tung, T.; Wallbank, J.A.; Fraser, K.; Miles-Chan, J.L.; Poppitt, S.D.; Taylor, M.W. Investigating Multi-Omic Signatures of Ethnicity and Dysglycaemia in Asian Chinese and European Caucasian Adults: Cross-Sectional Analysis of the TOFI_Asia Study at 4-Year Follow-Up. Metabolites 2025, 15, 522. https://doi.org/10.3390/metabo15080522
Faraj S, Joblin-Mills A, Sequeira-Bisson IR, Leiu KH, Tung T, Wallbank JA, Fraser K, Miles-Chan JL, Poppitt SD, Taylor MW. Investigating Multi-Omic Signatures of Ethnicity and Dysglycaemia in Asian Chinese and European Caucasian Adults: Cross-Sectional Analysis of the TOFI_Asia Study at 4-Year Follow-Up. Metabolites. 2025; 15(8):522. https://doi.org/10.3390/metabo15080522
Chicago/Turabian StyleFaraj, Saif, Aidan Joblin-Mills, Ivana R. Sequeira-Bisson, Kok Hong Leiu, Tommy Tung, Jessica A. Wallbank, Karl Fraser, Jennifer L. Miles-Chan, Sally D. Poppitt, and Michael W. Taylor. 2025. "Investigating Multi-Omic Signatures of Ethnicity and Dysglycaemia in Asian Chinese and European Caucasian Adults: Cross-Sectional Analysis of the TOFI_Asia Study at 4-Year Follow-Up" Metabolites 15, no. 8: 522. https://doi.org/10.3390/metabo15080522
APA StyleFaraj, S., Joblin-Mills, A., Sequeira-Bisson, I. R., Leiu, K. H., Tung, T., Wallbank, J. A., Fraser, K., Miles-Chan, J. L., Poppitt, S. D., & Taylor, M. W. (2025). Investigating Multi-Omic Signatures of Ethnicity and Dysglycaemia in Asian Chinese and European Caucasian Adults: Cross-Sectional Analysis of the TOFI_Asia Study at 4-Year Follow-Up. Metabolites, 15(8), 522. https://doi.org/10.3390/metabo15080522