Aspartame is a commonly used artificial sweetener. It was first recommended to reduce total caloric intake, but it was later suspected of having potentially damaging health effects.
Study
The current study's authors explored the possibility that aspartame could worsen the prognosis in GBM. They used advanced tools to analyze the metagenomics and transcriptomics of a GBM mouse model.
Gliomas were induced using cancerous cells transplanted into healthy mice. These were then exposed to aspartame in drinking water, with an aspartame-free control group. The aim was to understand better how aspartame affects the tumor prognosis via the gut microbiome.
Findings
The results indicate that tumor growth remained unchanged despite aspartame consumption. However, the gut microbiome underwent a significant change. The abundance of bacteria belonging to the Rikenellaceae family was reduced.
Essential genes in the N6-methyladenosine-regulated pathway were expressed at higher levels in the aspartame-exposed mice. These included cyclin-dependent kinase inhibitor 1A (CDKN1A), MYC (myelocytomatosis) oncogene, and transforming growth factor-β (TGFB1).
The increased expression of TGFB1, a known marker of adverse prognosis in glioblastoma, may indicate an unfavorable molecular profile in aspartame-exposed tumors. Although tumor size did not increase, aspartame may influence gene expression patterns associated with more aggressive disease. This elevated expression could be due to changes in RNA methylation along the N6-methyladenosine pathway. However, more research is needed to confirm these effects in humans.
Conclusion
For the first time, this study showed that the gut microbiome is affected by the presence of aspartame, both in composition and abundance. This is in keeping with earlier findings showing that volatile fatty acids like acetic and propionic acid impact the gut microbes, especially Rikenellaceae. This family is connected to multiple metabolic health disorders, such as non-alcoholic fatty liver disease and Parkinson’s disease.
Though there was no evidence that the tumor grew faster when the mice were exposed to aspartame, the changes in the gut microbiome were noticeable, primarily the reduction in Rikenellaceae. This could alter tumor progression via its eventual impact on the gut-brain axis.
Aspartame intake also increased methylation in the N6-methyladenosine pathway and upregulated associated genes. This suggests that this pathway plays a key role in gene regulation, especially of genes implicated in cancer progression like MYC, CDKN1A, and TGFB1. These reflected N6-methyladenosine peaks, indicating that these genes may represent potential targets influenced by aspartame-related epigenetic changes.
“These insights open new avenues for GBM treatment strategies, including gene-targeted therapies and microbial-based interventions, among others.”
However, the study had limitations. It involved a small sample size, used only female mice, and did not explore the impact of aspartame metabolites or the intratumoral microbiome. These factors may be necessary to clarify the precise mechanisms involved in future research. In addition, as a preclinical study conducted in mice, the findings cannot yet be directly generalized to human health outcomes.
Future studies will explore the role played by aspartame metabolites and the microbiome within the tumor in mediating this compound's effects.
Source:
https://www.news-medical.net/news/20250708/Aspartame-triggers-genetic-changes-tied-to-glioblastoma-severity.aspx