Modern research has revealed that the intestine is not merely a digestive organ but also one of the most important centers of immune communication in the body. It is estimated that between 60% and 70% of peripheral immune cells are associated with the gastrointestinal tract, where they constantly interact with the microorganisms that make up the intestinal microbiota.
This interaction is not accidental. Intestinal bacteria produce a wide variety of bioactive molecules capable of influencing the maturation of dendritic cells (the cells that monitor and alert the immune system to potential threats), the activation of T lymphocytes (the elite cells of the immune response), the function of NK cells (the body’s first line of defense), and the regulation of inflammatory processes. In essence, the microbiome helps train the immune system to distinguish between real threats and harmless stimuli.
When this relationship becomes disrupted, immune imbalances may develop that are associated with inflammatory diseases, metabolic disorders, and even cancer. For this reason, an increasing number of researchers consider maintaining a healthy microbiota to be an important component of immune homeostasis.
Why is bacterial diversity so important?
One of the most frequently discussed concepts in modern microbiology is microbial diversity. A healthy intestine typically contains hundreds of bacterial species coexisting in balance. This diversity allows different microorganisms to perform complementary functions, ranging from the fermentation of dietary fibers to the production of vitamins and immunomodulatory metabolites.
Numerous studies have found that reduced bacterial diversity is associated with conditions such as obesity, type 2 diabetes, inflammatory bowel disease, and certain types of cancer. In addition, patients exposed to aggressive treatments, prolonged antibiotic use, or diets low in fiber often experience a significant reduction in microbial diversity.
For this reason, many modern nutritional strategies seek not only to increase the abundance of a specific bacterial species but also to support a more diverse and resilient microbial ecosystem.
As our understanding of the gut microbiome continues to expand, so does interest in strategies capable of promoting a more diverse and functional microbial community. Among the most studied approaches are probiotics and prebiotics.
Although these terms are often used together, they do not mean the same thing. Probiotics are live microorganisms that, when administered in adequate amounts, may provide health benefits. Prebiotics, on the other hand, are non-digestible compounds, typically fermentable fibers, that serve as food for beneficial bacteria already present in the intestine.
The relationship between the two is closely interconnected. Introducing beneficial bacteria through probiotics can be helpful, but these microorganisms require a suitable environment in order to thrive and persist. Prebiotics provide precisely that fuel, supporting the production of metabolites that benefit intestinal and immune health.
For this reason, many researchers believe that combining probiotics and prebiotics may offer greater benefits than either approach alone, a strategy known as synbiotic supplementation.
Bifidobacterium: Much more than a beneficial bacterium
Species belonging to the genus Bifidobacterium are among the most extensively studied microorganisms within the human microbiome. They are particularly abundant during infancy but continue to play important roles throughout life.
These bacteria help ferment complex fibers that the human body cannot digest on its own. As a result, they generate beneficial metabolites such as acetate and lactate, which can subsequently be utilized by other intestinal bacteria to produce butyrate.
In addition, certain Bifidobacterium species may enhance dendritic cell function, promote more efficient immune responses, increase cytotoxic T-cell activity, and improve responses to immune checkpoint inhibitor therapies.
These findings have generated significant interest in multi-strain probiotic formulations designed to promote the presence of bacteria associated with more favorable immune profiles. One example is the use of probiotics containing multiple strains of Bifidobacterium, which aim to increase bacterial diversity and support the production of beneficial metabolites within the intestinal ecosystem.
Butyrate: One of the most important molecules produced by the microbiome
When discussing the benefits of prebiotics, many of their effects are linked to the production of short-chain fatty acids, particularly butyrate.
Butyrate serves as a critical energy source for colon cells and contributes to maintaining the integrity of the intestinal barrier. However, its functions extend far beyond digestive health.
Numerous studies have demonstrated that butyrate can modulate immune cell activity, reduce excessive inflammation, and participate in epigenetic mechanisms that regulate gene expression. It has also been associated with improved metabolic function and enhanced insulin sensitivity.
For this reason, many microbiome-supportive strategies seek to increase butyrate production through the consumption of fermentable fibers such as inulin and fructo-oligosaccharides (FOS). These compounds serve as nourishment for beneficial bacteria and promote the generation of metabolites associated with improved intestinal and immune health.
Other sources of prebiotic fiber, such as kiwi-derived extracts rich in fermentable compounds, have also attracted attention for their ability to support microbial diversity and digestive function.
Other species, such as Akkermansia muciniphila, have generated enormous scientific interest. This bacterium appears to contribute to the maintenance of the intestinal barrier and has been associated with improved metabolic profiles in multiple clinical and experimental studies. Individuals with higher levels of Akkermansia often demonstrate better insulin sensitivity, lower systemic inflammation, and a more favorable metabolic profile.
Figure 1. Prebiotics feed beneficial gut bacteria, while probiotics introduce beneficial microorganisms. Together, they support microbial diversity, SCFA production, immune regulation, intestinal barrier function, and metabolic health.
Bacterial diversity and intestinal resilience
Modern research indicates that bacterial diversity is one of the strongest indicators of a healthy microbiome. For this reason, many formulations combine multiple species of Lactobacillus and Bifidobacterium with the goal of supporting a more robust and resilient intestinal ecosystem.
This approach seeks not only to introduce beneficial microorganisms but also to support the overall balance of the microbiota against factors that may disrupt it, including stress, low-fiber diets, antibiotic exposure, and certain diseases.
The combined use of probiotics, prebiotics, and personalized nutritional strategies may play an increasingly important role in promoting digestive, metabolic, and immune health.
The microbiome and the future of immunotherapy
Numerous studies have observed that patients who respond favorably to anti-PD-1 or anti-CTLA-4 therapies often display distinct microbial profiles compared to those who do not respond. Among the bacteria most frequently associated with improved outcomes are Bifidobacterium longum, Akkermansia muciniphila, Faecalibacterium prausnitzii, and various members of the Ruminococcaceae and Lachnospiraceae families.
Although there is not yet a “probiotic for immunotherapy,” these findings suggest that microbiome composition could become an important biomarker for personalized medicine. Evaluating not only tumor mutations and immune biomarkers, but also the composition of the intestinal microbiota before initiating specific therapies, may improve precision in cancer care.
What was once considered merely a collection of intestinal bacteria is now emerging as one of the most influential biological systems in human health, with implications ranging from metabolism and inflammation to cancer immunotherapy.
This article is intended solely for educational and informational purposes. It is not intended to provide medical advice, diagnosis, or treatment recommendations. Readers should consult qualified healthcare professionals regarding any medical concerns or decisions related to their health.
Main reference:
Kang, X., Lau, H. C., & Yu, J. (2024). Modulating gut microbiome in cancer immunotherapy: Harnessing microbes to enhance treatment efficacy. Cell reports. Medicine, 5(4), 101478. https://doi.org/10.1016/j.xcrm.2024.101478
Other references:
Lei, W., Zhou, K., Lei, Y., Li, Q., & Zhu, H. (2025). Gut microbiota shapes cancer immunotherapy responses. NPJ biofilms and microbiomes, 11(1), 143. https://doi.org/10.1038/s41522-025-00786-8
Yoo, S., Jung, S. C., Kwak, K., & Kim, J. S. (2024). The Role of Prebiotics in Modulating Gut Microbiota: Implications for Human Health. International journal of molecular sciences, 25(9), 4834. https://doi.org/10.3390/ijms25094834
