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Tianxi Yan1, Qiqi He1, Xueli Shi1
1Zhuang Medicine College, Guangxi University of Chinese Medicine, Nanning 530001, China.
International Journal of Molecular Sciences
|July 15, 2026
Summary
This study explored potential molecular links between the artificial sweetener aspartame and rheumatoid arthritis (RA). It identified 16 core genes, including HLA-DRB1, suggesting a hypothesis-generating association requiring further validation.
Area of Science:
- Computational biology and bioinformatics
- Immunogenetics
- Molecular toxicology
Background:
- The relationship between aspartame consumption and rheumatoid arthritis (RA) is not well understood.
- Aspartame is a common artificial sweetener with potential biological targets.
- RA is a chronic autoimmune disease affecting joints, with complex genetic and environmental factors.
Purpose of the Study:
- To investigate potential molecular connections between aspartame targets and RA-associated gene networks.
- To identify core genes and pathways potentially linking aspartame to RA pathogenesis.
- To generate hypotheses for future experimental and clinical research.
Main Methods:
- Integration of multiple RA transcriptomic datasets (GEO: GSE55235, GSE55457, GSE77298) with batch correction.
- Identification of differentially expressed genes (DEGs) in RA and intersection with predicted aspartame targets.
- Machine learning (113 algorithms) to identify optimal multigene diagnostic models and core genes.
- Virtual knockout of HLA-DRB1 and molecular docking to assess aspartame-HLA-DRB1 interaction.
Main Results:
- Forty-four intersected genes linked predicted aspartame targets with RA DEGs.
- A random forest plus partial least-squares generalized linear model (RF + plsRglm) identified 16 core genes.
- Network analysis revealed gene distribution across immune, inflammatory, metabolic, and other modules.
- Molecular docking indicated potential interaction between aspartame and HLA-DRB1 (binding energy -6.7 kcal/mol).
Conclusions:
- This integrative analysis suggests a hypothesis-generating association between aspartame-related targets and RA molecular networks, involving HLA-DRB1 and other core genes.
- The findings highlight potential roles in immune/antigen processing, inflammation, and extracellular matrix remodeling.
- Further experimental, epidemiological, and biophysical validation is required to establish causality.
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