The 14th edition of the Gut Microbiota for Health World Summit brought together leading researchers from around the world to present the latest advances in the field. The meeting introduced new, still emerging microbiome-targeted therapies in cancer. Work presented by Dr. Gianluca Ianiro, Dr. Lisa Derosa, and Dr. Miguel Zugman highlighted not only major scientific progress but also the importance of large-scale collaboration.
Why cancer outcomes vary: beyond genetics and treatment
Cancer is now one of the leading causes of death in developing countries. Clinicians are also increasingly concerned about a rise in early-onset cancers, occurring in younger individuals who are often outside current screening programs. For most cancers that are not driven by genetics, the causes remain complex and not fully understood. They likely involve a combination of environmental exposures, diet, physical activity, stress, sleep, and other lifestyle factors.
Over the years, several treatments have been developed to fight cancer, including chemotherapy, radiotherapy, and hormone therapy. More recently, immunotherapy has emerged as a major breakthrough. To understand how it works, it is important to know that our immune system constantly detects and eliminates abnormal cells. Cancer cells, however, can escape this surveillance by “hiding” from the immune system. Immunotherapy aims to reactivate immune cells so they can recognize and eliminate cancer cells again. While some patients respond very well to immunotherapy, sometimes achieving long-term remission, others do not respond at all. Understanding why remains one of the key challenges in cancer research today.
Gut microbiota: a key player in immunotherapy response
This is where the gut microbiota comes into play. The collaborative work of Dr. Gianluca Ianiro, Dr. Lisa Derosa, and Dr. Miguel Zugman focuses on understanding why patients respond differently to immunotherapy and how the gut microbiota may influence this response.
One important observation is that patients who receive antibiotics tend to not respond to immunotherapy. This suggests that disrupting the gut microbiota may reduce the effectiveness of these treatments. This is particularly relevant because many cancer patients receive antibiotics during their care.
To investigate further, these teams analyzed large cohorts of patients across multiple studies, including cancers located outside the gut such as skin and kidney cancer. They identified specific patterns in the gut microbiota associated with treatment response. For example, certain bacterial groups were more abundant in patients who did not respond well to immunotherapy, while others were associated with better outcomes.
One bacterium, Akkermansia muciniphila, emerged as a key marker linked to microbiota balance and treatment response. Based on these large datasets, researchers developed a predictive tool called the TOPOscore, which aims to estimate the likelihood of responding to treatment and possibly the risk of disease based on microbiota composition. These tools are still under development but illustrate the move toward more personalized medicine.
Can fecal microbiota transplantation improve cancer treatment outcomes?
Given the strong link between the gut microbiota and treatment response, researchers explored whether modifying the microbiota could improve outcomes. Fecal microbiota transplantation, or FMT, is a procedure that transfers gut microbes from a healthy donor to a patient. It is already highly effective in treating Clostridioides difficile infections. Researchers have therefore tested whether FMT could also help cancer patients undergoing immunotherapy.
In patients with melanoma, FMT has been shown to improve response to immunotherapy in some cases, leading to better outcomes. Ongoing studies, including in kidney cancer, suggest that FMT can influence immune cell activity, supporting its potential role in cancer treatment.
However, FMT has important limitations. It is difficult to standardize, depends on donor availability, and raises practical and regulatory challenges. Questions remain about how it should be administered, when it should be used, and how to ensure consistent results. For these reasons, researchers are now looking beyond FMT toward more controlled approaches.
From FMT to precision therapies: the rise of targeted microbiome interventions
The next step is to develop more precise treatments based on live biotherapeutics.
Based on microbiota analyses, researchers identified bacteria that are often missing or reduced in patients who do not respond to immunotherapy. Clinical trials have tested some of these bacteria as treatments. These results were presented during the summit but have not yet been published. For example, a bacterial strain known as CBM588 showed improved responses to immunotherapy in patients with kidney cancer. Similarly, trials using Faecalibacterium prausnitzii in lung and gastric cancers have shown promising results.
These bacteria are known to produce beneficial compounds and support immune function. Interestingly, their effects do not require permanent colonization of the gut. Even temporary changes in the microbiota appear sufficient to stimulate the immune system and improve treatment response.
Protecting the microbiome: a new frontier in cancer care
An important takeaway from this research is that preserving or modifying the gut microbiota is critical for optimizing cancer therapies. For example, antibiotic use can negatively impact treatment response, highlighting the need for careful clinical decisions. While FMT has demonstrated potential, the field is now moving toward more precise, scalable, and controlled interventions based on specific live biotherapeutics. Overall, these advances suggest that targeting the gut microbiota could become an important component of cancer treatment in the future.
