{"id":835,"date":"2023-06-06T08:12:07","date_gmt":"2023-06-06T08:12:07","guid":{"rendered":"https:\/\/website.prod.unilu.spikeseed.cloud\/fstm-fr\/news\/from-microfluidics-to-mouse-models-to-study-microbiome-in-cancer\/"},"modified":"2023-06-06T08:12:07","modified_gmt":"2023-06-06T08:12:07","slug":"from-microfluidics-to-mouse-models-to-study-microbiome-in-cancer","status":"publish","type":"news","link":"https:\/\/www.uni.lu\/fstm-fr\/news\/from-microfluidics-to-mouse-models-to-study-microbiome-in-cancer\/","title":{"rendered":"From microfluidics to mouse models to study microbiome in cancer"},"content":{"rendered":"

Colorectal cancer is one of the most frequent types of cancer worldwide, ranking third in terms of incidence and second in mortality. In the past decade, the gut microbiome, the group of microorganisms that inhabit our digestive tract, has been identified as a key player in colorectal cancer. However, the underlying mechanisms remain largely unexplored and there is an urgent need to move beyond descriptive studies when it comes to the interactions between gut bacteria and tumour cells.<\/p>

In a Nature metabolism<\/i>, researchers from the University of Luxembourg show that a molecule secreted by a specific bacterium induces tumour growth and contributes to the progression of the disease. The study integrates in vitro, in vivo and in silico approaches. It highlights how animal research, combined with sophisticated methods, such as organoids and gut-on-chip models, helps gain a mechanistic understanding of cancer pathogenesis.<\/p>

Prof. Elisabeth Letellier<\/a>, head of the\u00a0Molecular Disease Mechanisms<\/a>\u00a0team at the\u00a0Department of Life Science and Medicine<\/a>\u00a0(DLSM) of the University of Luxembourg and project supervisor of the article, explains: \u201cWe rely on several approaches in a study like this one. Over time, scientists have developed cutting-edge techniques to mimic biological systems in the lab but none of them can fully reproduce the complexity of a living organism. We need mouse models to account for all of the existing parameters, especially in oncology where the interactions between different cell types are key and the whole microenvironment drives the disease.\u201d<\/p>

In this study, samples given by patients allowed the researchers to determine which microorganisms are associated with colorectal cancer and to identify a bacterium of interest:\u00a0Fusobacterium nucleatum<\/i>. Then, microfluidics devices, in which human cancer cells and bacteria are cultivated together, helped determine the effects of\u00a0F. nucleatum<\/i>\u00a0and of a molecule it produces – formate. After studying the disease mechanisms in detail in the lab, the team was able to validate their findings thanks to animal models. Experiments in mice confirmed that the presence of the bacterium in the gut leads to increased tumour burden through the production of formate.<\/p>

These results constitute a step forward in understanding the complex interactions between the gut microbiome, the molecules it secretes and cancer metabolism, which will help to develop microbiome-based therapies in the future. They also underline that mouse models remain the gold standard in cancer research. \u201cI think it is important to underline that we still need animal research: we are not there yet with the alternatives and it will be a long time before we can fully replace animal models,\u201d details Prof. Letellier. \u201cWe need to be open about this and to ensure that we are doing everything the right way.\u201d<\/p>

Animal research has improved a lot over time. In the twenty years that she has been working with mice, Elisabeth Letellier has seen major improvements in terms of animal welfare and\u00a0ethics<\/a>. For example, the University of Luxembourg follows the\u00a03R principles<\/a>. Researchers look for alternatives when possible, refine protocols to minimise pain and reduce the number of animals by using statistical methods and advanced equipment. Among the recent and upcoming improvements, the installation of cages with an automated monitoring system<\/a> and the purchase of an\u00a0in vivo<\/i>\u00a0multiphoton laser-scanning microscope. The latter will allow scientists to observe the evolution of a disease over time in the same mouse, decreasing the number of animals needed. In addition to these technical transformations, the animal research mindset has evolved as well. \u201cEverybody now understands that we have to strike a balance between our research objectives and animal welfare,\u201d concludes Prof. Letellier. \u201cAnd that to achieve it, researchers, vets, caretakers and members of the ethics committee have to work hand-in-hand. This is how we will keep pushing the boundaries of biomedical research.\u201d<\/p>

—<\/p>

Reference: Ternes D., Tsenkova M., Pozdeev V.I. et al.,\u00a0The gut microbial metabolite formate exacerbates colorectal cancer progression<\/strong><\/a>,\u00a0https:\/\/doi.org\/10.1038\/s42255-022-00558-0<\/a>, 4, 458\u2013475 (2022).\u00a0Nature Metabolism<\/i><\/p>

Illustration created with BioRender.com<\/p><\/div><\/section>","protected":false},"excerpt":{"rendered":"

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