Aspartame triggers genetic changes that are linked to the severity of glioblastoma

Aspartame triggers genetic changes that are linked to the severity of glioblastoma

Despite no visible tumor growth, new research finds that the artificial sweetener aspartame remodels gut bacteria and upregulates cancer-linked genes in glioblastoma.

Study: Metagenomics and transcriptomics analysis of the impact of aspartame on the progression of gut microbiota and glioblastoma in a mouse model. Photo credit: Pheelings Media/Shutterstock.com

Aspartame is a commonly used artificial sweetener. It was initially recommended to reduce total calorie intake, but was later suggested to have potentially harmful health effects. A recently published study inScientific reportsindicates that its use is associated with molecular changes associated with a worse prognosis in cases of glioblastoma multiforme (GBM).

introduction

Aspartame dates back to the 1960s. It is commonly used in low sugar drinks and chewing gum, as well as some cough syrups and chewable vitamins. The joint report of the International Agency for Research on Cancer (IARC) and the joint FAO (Food and Agriculture Organization of the United Nations)/WHO (World Health Organization) Expert Committee on Food Additives (JECFA) has declared them as possibly carcinogenic studies for daily daily intake for daily daily intake for daily investigation from 0 to 40 mg/kg.

GBM is a leading killer of primary brain cancers, causing both the most aggressive tumor and the most likely death. It grows rapidly and is intractable to conventional cancer treatments. It also suppresses the immune response in its tumor microenvironment.

Aspartame may not be as safe as sugar. Several studies have suggested that intake increases the risk of several cancers, colon, brain, reproductive system and blood. Its consumption is also associated with the development of headaches. However, some research has shown conflicting results and further studies are needed to clarify the risk.

Food additives such as aspartame can affect memory, possibly by collaborating with others. Previous studies have failed to link high levels of aspartame from diet drinks to blood cancer or glioma risk. However, aspartame may directly influence the gut microbiome and thus mediate the risk of glioblastoma via the gut-brain axis.

This axis influences immunity and metabolic pathways in the immediate tumor microenvironment. For example, the gut microbiota produces mainly short-chain fatty acids (SCFA) such as butyrate and other molecules such as tryptophan, which themselves are cellular activators. They stimulate cell receptors and initiate metabolic pathways within the cell.

The opposite also occurs, whereby the tumor microenvironment signals and inhabits the gut microbiome via the microbial community in the tumor. These microbes promote tumor development by facilitating genomic instability, suppressing immune recognition of tumor antigens, and aberrant metabolic pathways.

For example, bacterial DNA is found in GBM tumors. Its effect on gene expression and regulation within the developing tumor remains unclear. However, tumor microbiota is likely to provide novel therapeutic and diagnostic targets for cancer management.

Another area of ​​interest is the influence of epigenetic modifications, particularly the N6-methyladenosine modification, in messenger RNA (mRNA). This is closely linked to metabolism and to the gut microbiota, which in turn suggests a mediator of the connection between glioma progression and the gut.

About the study

The authors of the current study investigated the possibility that aspartame might worsen the prognosis in GBM. They used advanced tools to analyze the metagenomics and transcriptomics of a GBM mouse model.

Gliomas were induced using cancer cells transplanted into healthy mice. These were then exposed to aspartame in drinking water with an aspartame-free control group. The aim was to better understand how aspartame affects tumor prognosis via the intestinal microbiome.

Study results

The results suggest that tumor growth remained unchanged despite aspartame consumption. However, the gut microbiome underwent a significant change. The abundance of bacteria that leads to theRikenellaceaeThe family was reduced.

Essential genes in the N6-methyleneosine-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 well-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 increased expression could be due to changes in RNA methylation along the N6-methyladenosine pathway. However, further research is needed to confirm these effects in humans.

Diploma

For the first time, this study showed that the gut microbiome is influenced by the presence of aspartame in both composition and abundance. This is consistent with previous findings showingRikenellaceae. This family is associated with several metabolic disorders such as nonalcoholic fatty liver disease and Parkinson's disease.

Although there was no evidence that the tumor grew faster when the mice were exposed to aspartame, the changes in the gut microbiome wereRikenellaceae. This could alter tumor progression through its eventual effects on the gut-brain axis.

Aspartame intake also increased methylation in the N6-methyleneosine pathway and upregulated associated genes. This suggests that this pathway plays a key role in gene regulation, particularly genes involved in cancer progression such as Myc, CDKN1A and TGFB1. These reflected the N6-methyladenosine peaks, indicating that these genes may represent potential targets affected by aspartame-related epigenetic changes.

“These findings open up new avenues for GBM treatment strategies, including gene-targeted therapies and microbial interventions, among others. “”

However, the study had limitations. It was a small sample size, using only female mice, and did not examine the influence of aspartame metabolites or the intratumoral microbiome. These factors may be necessary to clarify the exact mechanisms of future research. Furthermore, as a preclinical study conducted in mice, the results cannot yet be directly generalized to human health outcomes.

Future studies will examine the role of aspartame metabolites and the microbiome within the tumor in mediating the effects of this compound.

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