The rapid rise of adults taking GLP-1RA medications (e.g., Wegovy, Ozempic, Mounjaro) in the U.S. (16 million and counting) and around the world has been accompanied by a slew of the drugs’ proclaimed health benefits. Weight loss is a common (and extremely popular) side effect, making GLP-1RAs some of the most exciting weapons in the arsenal for battling the obesity epidemic. Loss of unhealthy visceral fat and improved blood sugar control are just two of the downstream effects of this weight loss, which, in turn, promise their own health benefits.

But what do we really know about the long-term impacts of GLP-1RA medications? Researchers caution us not to get ahead of ourselves when it comes to the logical, though still theoretical, possibilities of how these drugs may influence related health conditions such as cancer. 

Per- and polyfluoroalkyl substances (PFAS), manmade chemicals that accumulate in the body over time, have been linked to liver disease and cancer, but it is not yet clear how they cause damage. USC researchers used a lab model of the human liver to analyze changes at the cellular level, finding that some PFAS triggered fat accumulation and others caused cell damage linked to cancer. The researchers used spheroids, sophisticated 3D models that recreate the structure of the liver using cells from 10 human donors (five male and five female). They exposed the spheroids to four types of PFAS commonly found at high levels in the blood: perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS), perfluorooctanesulfonic acid (PFOS) and perfluorononanoic acid (PFNA). Each chemical was tested separately to determine its specific effects on liver cells. After seven days of exposure, the researchers separated the spheroids into individual cells for analysis. They used single-cell RNA sequencing to analyze gene expression and a dye-based method to measure fat buildup in the spheroids under a microscope. All four PFAS interrupted cell signaling and immune functions, but exact changes varied from one chemical to the next. Both PFOA and PFHxs increased fat accumulation—PFOA by causing cells to produce more fat and PFHxS by causing cells to retain fat. Both PFOS and PFNA triggered cancer-related changes in cells, but PFNA had a stronger effect, increasing activity in cellular pathways related to inflammation, oxidative stress and DNA repair. Of the cells exposed to PFNA, 61.3% showed gene changes linked to cancer. The researchers also found that liver cells from male and female donors responded differently to PFAS exposure. PFOA has stronger effects on female liver cells, while PFOS had stronger effects on cells from male donors.

An international team of scientists led by researchers at the MRC Laboratory of Medical Sciences (LMS), Imperial College London and the University of Cologne have discovered that microbes associated with tumours produce a molecule, which can control cancer progression and boost the effectiveness of chemotherapy.

Most people are familiar with the microbes on our skin or in our gut, but recent discoveries have revealed that tumours also host unique communities of bacteria. Scientists are now investigating how these tumour-associated bacteria can affect tumour growth and the response to chemotherapy. 

New research, published online in Cell Systems on 10 September 2025, provides a significant breakthrough in this field, identifying a powerful anti-cancer metabolite produced by bacteria associated with colorectal cancer. This finding opens the door to new strategies for treating cancer, including the development of novel drugs that could make existing therapies more potent. 

The researchers used a sophisticated large-scale screening approach to test over 1,100 conditions in a type of microscopic worm called C. elegans. Through this, they found that the bacteria E. coli produced a molecule called 2-methylisocitrate (2-MiCit) that could improve the effectiveness of the chemotherapy drug 5-fluorouracil (5-FU). 

Using computer modelling, the team demonstrated that the tumour-associated microbiome (bacteria found within and around tumours) from patients was also able to produce 2-MiCit. To confirm the effectiveness of 2-MiCit, the team used two further systems; human cancer cells and a fly model of colorectal cancer. In both cases, they found that 2-MiCit showed potent anti-cancer properties, and for the flies could extend survival. 

Professor Filipe Cabreiro, head of the Host-Microbe Co-Metabolism group at the LMS, and group leader at the CECAD Research Cluster in Cologne, explains the significance of the discovery: “We've known that bacteria are associated with tumours, and now we're starting to understand the chemical conversation they're having with cancer cells. We found that one of these bacterial chemicals can act as a powerful partner for chemotherapy, disrupting the metabolism of cancer cells and making them more vulnerable to the drug.” 

The study revealed that 2-MiCit works by inhibiting a key enzyme in the mitochondria (structures inside cells that generate energy for cellular functions) of cancer cells. This leads to DNA damage and activates pathways known to reduce the progression of cancer. This multi-pronged attack weakens the cancer cells and works in synergy with 5-FU. The combination was significantly more effective at killing cancer cells than either compound alone. 

Dr Daniel Martinez-Martinez, postdoctoral researcher at the LMS and first author of the paper, says: “Microbes are an essential part of us. That a single molecule can exert such a profound impact on cancer progression is truly remarkable, and another piece of evidence on how complex biology can be when considering it from a holistic point of view. It is really exciting because we are only scratching the surface of what is really happening.” 

In collaboration with medicinal chemists, the researchers also modified the 2-MiCit compound to enhance its effectiveness. This synthetic version proved even more powerful at killing cancer cells, demonstrating the potential to develop new drugs based on natural microbial products. Filipe adds: “Using the natural microbial product as a starting point, we were able to design a more potent molecule, effectively improving on mother nature.” 

These exciting discoveries highlight how the cancer-associated microbiome can impact tumour progression, and how metabolites produced by these bacteria could be harnessed to improve cancer treatments. These findings are also important in the context of personalised medicine, emphasising the importance of considering not only the patient, but also their microbes. 

This study was primarily funded by the Leverhulme Trust, the Wellcome Trust/Royal Society, the DFG German Research Foundation, and the Medical Research Council.