In recent years, immunotherapy has transformed the landscape of cancer treatment. Therapies such as PD-1 inhibitors (proteins that function as a natural brake on the immune system) have allowed the body’s defenses to activate and recognize tumor cells. Thanks to them, thousands of patients have experienced surprising remissions in types of cancer that were previously almost impossible to treat. However, this therapeutic revolution faces a great challenge: not all patients respond in the same way. While some achieve lasting benefits, others show barely any improvement. Understanding the reasons behind this difference is one of the great challenges of modern medicine.

A recent study carried out by Japanese researchers and published in the prestigious journal Nature (2025) offers a fascinating clue: the key could lie in the intestine. As mentioned in previous blogs, our body harbors trillions of microorganisms that make up the gut microbiota, a microscopic ecosystem that influences digestion, metabolism, mental health, and, as is increasingly evident, also immunity. The researchers discovered that the composition of this microbiota can largely determine how well a person responds to immunological therapies against cancer and, in particular, they identified a new bacterium, Hominenteromicrobium mulieris YB328, which seems to have the ability to “train” the immune system to better recognize tumors.

What is interesting about this finding is not simply that the microbiota is indirectly related to immunotherapy, something already mentioned in multiple studies, but that the research team managed to show the mechanism step by step. The bacterium YB328 interacts in the intestine with immune cells called dendritic cells, which function as messengers or “teachers” of the immune system. These dendritic cells, when maturing under the influence of YB328, migrate to the lymph nodes and finally to the tumor microenvironment. Once there, they present antigens (small fragments of the tumor that act as “identity signals” of it) to CD8+ T lymphocytes, which are the soldiers responsible for destroying cancer cells. In other words, the gut microbiota does not remain in the intestine: its action extends to the tumor itself, reinforcing the effectiveness of treatments based on PD-1 inhibition.

However, not every bacterium is beneficial, and this became clear when contrasted with other common species in the intestine, such as Phocaeicola vulgatus, which showed the opposite effect. In patients where this bacterium predominated, the results against immunotherapy were much worse: there was less infiltration of defensive T cells and an increase in regulatory cells that slow down the immune response. Even in animal models, the administration of P. vulgatus reduced the effectiveness of PD-1 inhibitors and even blocked the positive effect of YB328 when both bacteria were present. This finding highlights a critical aspect: not all bacteria are allies in the fight against cancer, and some can hinder treatments.

The study went even further by showing that the diversity of the gut microbiota as a whole is also important. Patients who responded better to immunotherapy not only had more YB328 but also a greater richness and variety of bacteria. This finding coincides with a growing idea in medicine: a more diverse intestinal ecosystem is synonymous with greater resilience and balance, which translates into health benefits in general and, in this case, into the effectiveness of cancer treatment. In fact, the analysis revealed that bacterial families such as Ruminococcaceae were associated with greater survival (which thrive on a diet rich in plant fiber, whole grains, and resistant starches), while others such as Bacteroidaceae were linked to worse results (they increase with diets high in fat and animal protein, and low in fiber).

Fig. 1. H. mulieris YB328 stimulates antitumor dendritic cells, activating CD8⁺ T cells and boosting therapy effectiveness. In contrast, P. vulgatus promotes suppressive dendritic cells and Tregs, leading to exhausted CD8⁺ T cells and a weakened immune response.

In experiments with animals, the results were compelling; mice treated with fecal transplants from patients who had responded well to immunotherapy showed significant improvement against cancer, while those that received microbiota from non-responder patients obtained no benefits. However, when YB328 was added to these samples, the situation changed and the mice regained the ability to respond to PD-1 inhibitors. This demonstrates that the action of YB328 can be dominant and that its presence can reverse the resistance initially imposed by an unfavorable microbiota.

All of this leads us to a powerful conclusion: the gut microbiota is not a passive actor in our health, but an active modulator of the immune system. The interaction between gut bacteria and dendritic cells shows that what happens in the intestine can have direct consequences in places as distant as a tumor in the lung or stomach. This finding opens up the possibility of new medical strategies. In the future, before starting immunotherapy, a patient’s gut microbiota could be analyzed as a biomarker to predict the probability of success. And beyond that, a “combined treatment” could be designed that not only includes the immunological drug but also a personalized intervention in the microbiome, whether through probiotics, prebiotics, diet, or even fecal transplants.

For now, YB328 is not available as a probiotic in clinics or pharmacies, and there is still a long way to go before it becomes part of a standard treatment. However, the results are promising and mark a clear trend in oncology research: gut health and cancer are intimately connected. Caring for and understanding the microbiota is no longer limited to talking about digestion or metabolism, but becomes an essential component of precision medicine and personalized therapies.

This study reminds us that we are more than human cells: we are a complex ecosystem where microorganisms play a vital role. The intestine, often called “the second brain,” could also be considered a key ally in the fight against cancer. As science advances, it is possible that the medicine of the future will combine drugs, immunotherapy, and manipulation of the microbiota to achieve more lasting and effective responses.

Main Reference: 

Lin, N. Y., Fukuoka, S., Koyama, S., Motooka, D., Tourlousse, D. M., Shigeno, Y., Matsumoto, Y., Yamano, H., Murotomi, K., Tamaki, H., Irie, T., Sugiyama, E., Kumagai, S., Itahashi, K., Tanegashima, T., Fujimaki, K., Ito, S., Shindo, M., Tsuji, T., Wake, H., … Nishikawa, H. (2025). Microbiota-driven antitumour immunity mediated by dendritic cell migration. Nature, 10.1038/s41586-025-09249-8. Advance online publication. https://doi.org/10.1038/s41586-025-09249-8 

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