Postbiotics Found To Promote Anti-Cancer Immune Function

Probiotics, such as the capsules you can get at pharmacies containing different lactobacilli, carry live microorganisms that provide various health benefits. These are different from prebiotics, which can be any form of food or nutrition designed to promote the growth and activity of specific beneficial gut bacteria. In the gut, prebiotics are converted by gut bacteria into metabolites. The soluble metabolites that modulate the host environment are known as postbiotics. Postbiotics can include small molecules such as short-chain fatty acids, sugars, and different signaling molecules.

We are aware that there is a link between microbiota activity, cancer immunotherapy, and clinical outcome. For example, certain gut bacteria stimulate antigen-presenting cells, helping the immune system to become more active. We also observe that certain bacteria can stimulate the secretion of more cytokines by T cells.

There are many broad phenotypic changes that we currently observe in research. However, we are still quite far away from determining concrete mechanisms. This is because most of us in the field are still working with the microbiome as a whole. What we are doing in our research is trying to break that complexity down into smaller systems that we can understand.

There are trillions of bacteria, and all of them produce metabolites, making it very difficult to determine the effect of each metabolite or bacterium. We’re taking the approach of identifying the impact of a single metabolite on a single type of cell. We know from our work that for a single substance, such as pentanoate, at least three or four mechanisms are happening simultaneously. We’re trying to dissect these mechanisms for multiple metabolites in the hope that, by compiling this knowledge, we can predict what postbiotics are most beneficial to patients receiving CAR T-cell therapy.

When I was a PhD student, I was working in the field of autoimmunity and inflammation, and it was at the time when people had started looking into what metabolites are inducing or contributing to tolerogenic homeostasis in the gut. We had used pentanoate previously and found that it can inhibit inflammatory responses. From there, we decided to investigate how inflammatory T cells and anti-cancer T cells would respond when subjected to pentanoate.

The effect of pentanoate on improving the T cells' ability to defeat tumors was outstanding.

Over the last two to three years, many other groups have confirmed that pentanoate is important to immunotherapy success in patients.

As a basic research immunologist, my first question is always, how does something work? In cancer and treatment-focused research areas, it's more about how we can use something to benefit patients. Although this thought is correct, we can make the most optimal therapy when we understand how it works and what the mechanisms of those substances are.

In the real world, you don't have just one metabolite contributing to the overall effect of the microbiome. The most challenging aspect is identifying the metabolites that have beneficial effects and understanding the mechanisms in which they are involved. Once we've done that, I think the advantage is that these molecules are quite easy to synthesize.

Postbiotics can be easily incorporated into the culture of an engineered T cell and produced at GMP-grade level. They should also be compatible with many production protocols. 

These metabolites are not only of use for anti-cancer therapies, but also for therapies in the non-malignant space, for example, in tackling autoimmune diseases. However, how those molecules react is highly context-dependent. We need more data on the context in which the metabolites work. Once we have discovered the modes by which we can safely apply these postbiotics, then we will be on track to begin looking at implementing them in clinical trials.

This article is based on research findings that are yet to be peer-reviewed. Results are therefore regarded as preliminary and should be interpreted as such. Find out about the role of the peer review process in research here. For further information, please contact the cited source.