Research Explores Possible Link Between Gut Microbiome and Better Outcomes in Kidney Cancer

Nazli Dizman, MD

Gut microbiome diversities play a large role in modulating response to immunotherapy in patients with cancer, according to Nazli Dizman, MD, who gave presentation on the topic during the 2021 International Kidney Cancer Symposium (IKCS).

Microbial diversity is associated with better treatment outcomes characterized by changes in microbial species over the course of treatment, Dizman, an Internal Medicine residentat Yale Department of Internal Medicine explained during her presentation. This impacts the immune system either positively or negatively through one’s diet, probiotics, antibiotics and cancer treatments with evidence consistent across studies regardless of cancer type, therapeutic setting, cohort size and geography.

Future studies aim to look at the discrepancies that exist between clinically relevant species reported throughout different studies. By delving deep into different species and their biologic functions and assessing gut microbiome functionality will help us understand the connection between microbial communities and their outcomes.

In an interview with Targeted Oncology^TM, Dizman, discussed the role of gut microbiome in cancer and speaks to her presentation given at IKCS.

Targeted Oncology: Can provide a brief overview of your IKCS presentation around the role of the microbiome in cancer?

Dizman: There are trillions of bacteria that reside in our body and when you look at a man with 75 kilograms, they would have approximately 200 grams of bacteria in their body. So, microbiome is very important in many diseases, including cancers. There have been so many advancements in microbiome research recently, and we have a lot of data now linking outcomes with microbiome characteristics. This can include gut microbiome diversity, which has been consistently shown to be associated with better clinical outcomes in different cancer types, different cancer settings, different treatment settings, different cohorts, and different countries.

Gut microbiome diversities are playing an important role in modulating one's response to immunotherapy as a diverse microbiome is a better microbiome. There are also a few other species that were shown to be associated with response immunotherapies and targeted therapies too such as akkermansia muciniphila which has shown to be associated with better outcomes with immunotherapies in several cancer types, including renal cell carcinoma. Bacterial species are associated with worse outcomes when they are abundant in one school. Overall, there's still inconsistencies across different studies in terms of the association between certain species and the outcomes, but what is consistent across studies is the microbiome diversity. In my presentation, I also mentioned that antibiotics may have detrimental roles in a patient's response to immunotherapies again, and even with targeted therapies, we have some evidence showing their role as a determinant of response. It doesn't mean that we should refrain from antibiotics, but we should be using them very mindfully. Beyond that, now we have techniques to modulate gut microbiome.

Fecal microbiome transplantation has made an amazing success in small sample size studies. Investigators overcame immunotherapy resistance, investigators treated immune related colitis, with fecal microbiota transplant in patients with different types of cancers, and in addition to that, we recently presented results from a pilot randomized study in renal cell carcinoma patients. We randomized them into two groups where one group received a live bacterial product, and they demonstrated better clinical outcomes including better progression free survival and higher rates of response. So, there's a lot of exciting advancements happening in microbiome research. There's still a lot to learn and there's still a lot to do, but it's very exciting and I'll be mentioning the details or those points in my presentation at IKCS.

What role specifically does the microbiome play in cancers like renal cell carcinoma?

In general gut microbiome affects the immune system in different ways, including its metabolites going to circulation, stemming circulation, changing immune responses, with the presence of bacteria in tumor microenvironment and this way modulating immune-risk cancers. In renal cell carcinoma, we have a lot of data that has been done in the United States and in Europe in large cohorts looking at response characteristics and it looks like its determinant of better outcomes in renal cell carcinoma as well, beyond that microbial diversity which is so important. This has been shown in renal cell carcinoma to be associated with better outcomes with immunotherapy patients.

Also, our study that I mentioned where we attempted to modulate gut microbiome with live bacterial production obtained very interesting, impressive results in patients treated with this live bacterial product. In renal cell carcinoma where we have immunotherapies as the backbone of treatment, microbiome is going to play an important role and is playing an important role, and we investigators need to work a little bit more to understand how we can modulate and how we can use microbiome to help treat cancer.

What should community oncologists know about the microbiome when they're treating their patients?

When we treat our patients, mindful use of antibiotics is a key point. At this point, we have a very big reliable meta-analysis showing the mental effects of antibiotics on response to immunotherapies. I assume that community oncologists are probably getting questions about provider cues and even the use of live bacterial production given those impressive results that we obtained. So as an answer to those questions, we have limited data obtained from a small study, despite that it is very impressive. We are currently working on gut microbiome and trying to understand how we can modulate gut microbiome and perhaps get better outcomes in larger data sets. I think one thing to know is that research is still evolving, and there are a lot of unknown unknowns as well. Keeping track of what's happening in the field would be a recommendation from me to them as they might get questions from the patients about modulation. And if they have a close by center with clinical trials that evaluate gut microbiome or its modulation, referring interested patients into those places might be a recommendation as well.

What do you want oncologists to take away from your talk?

I think the key takeaway from my presentation is that gut microbiome diversity is probably the main thing that is causing the relationship between these outcomes and microbial characteristics. Beyond that, there are a few species that are shown to be associated with outcomes, but there are still a lot of discrepancies. In future studies, we'll work on assessing gut microbiome functionality, which can help us understand whether microbial communities cooperate and change the outcomes or modulate outcomes or different microbial species might have overlapping functional profiles and this might be the determinant of the outcomes.

_REFERENCE:

_{Dizman N. Role of the microbiome in Cancer. Presented at the International Kidney Cancer Symposium: North America. November 5-6, 2021; Austin, TX}