There has been an explosion of interest in the last decade in the interaction of the microorganisms in our gut with our bodies and overall health. More than half the cells in our body are not our own cells. They are instead the single cell microbes that reside in our gut, and there has been an explosion of interest in the last decade in they interact with our bodies and overall health.
We have a crucial symbiotic relationship with these microbes. We provide them with food, a safe home where they can multiply. They, in turn help us digest our food. In order for this relationship to be mutually beneficial, we have to have a biochemical “amnesty agreement” with them. When things are going well, we all remain healthy. When things are not going well gastrointestinal diseases, such as cholera or irritable bowel disease, emerge.
Over 300 different types of microbes have been found in the human gut, but 30 or so are more common there and part of a normal healthy gut ecosystem. Maintaining this as a mutual beneficial system requires a constant negotiation with our immune system. That, however, can be kicked off balance by what we ingest and whether it's contaminated with pathogens that take up residence in our guts solely for their own benefit and not ours.
All sorts of things can disrupt this internal ecosystem. This includes not only the normal foods we eat, but the microorganisms we ingested with them along with any medications we might be taking. It is well known that some foods and drugs can alter digestion causing constipation or diarrhea.
What has become clear in the last decade is that many drugs can interact with the gut microbial system through our immune system. That is where ADT comes in. In the last few years, it has been suggested that patients on ADT show some shift in the types and ratio of gut microbes. A study with mice suggested that one such microbe can enhance ADT’s effectiveness and possibly slow cancer progression. This has inspired a lot more interest in the relationship between ADT and our gut microbes.
A researcher has now examined how quickly the initiation of ADT leads to shifts in our gut microbial community. The author found that the shift was not immediate, but took more than a year to occur and stabilize.
So, what does this mean overall to the health of the patients on ADT, particularly in terms of cancer control?
Supposedly one might look at the gut microbes that are most common in patients on ADT, who have good cancer control and try to encourage the growth of those specific microbes in other patients on ADT.
There are at least two problems with that idea. First it assumes that the relationship between ADT’s effectiveness and the gut microbes is a simple and direct relationship. But we can't be sure of that. For instance, we know that ADT can change patients’ diabetic risk. Diabetes is a disease of the pancreas, which not only produces the hormone insulin (to help us process sugar in the body), but it also produces important chemicals that are injected into the gut to help aid digestion. As such, ADT might indirectly interact with the gut ecosystem through the function of the pancreas, changing the chemical environment of the gut ecosystem. That could, in turn, favors certain microbes over others.
If we find that certain microbes are beneficial for helping ADT control prostate cancer, the “best” microbes still have to work well in terms of our digestion. That means we must keep the complex ecosystem healthy, which involves a wealth of different species.
In sum, the evidence continues to grow that there is a relationship between the symbiotes in our gut, our immune system, and how well ADT works in controlling prostate cancer. But we don’t know if the relationship is directly causal or just some indirect correlative association involving all sorts of other variables that can be affecting our health overall.
Not just our own cells, but the community of other organisms that live in our guts, can impede, or enhance the effectiveness of medical treatments. However, we don’t know how to alter and then sustain the microbial community in a reproducible way that improves cancer control and concurrently keeps our gut microbial community our allies and not our enemies.
Reference:
Wang L. Changes in the gut microbial profile during long-term androgen deprivation therapy for prostate cancer. 2023 Sep 11. doi: 10.1038/s41391-023-00723-w. Epub ahead of print. PMID: 37696986.