The Microbiome at SABCS (Part 1)

Part 1: A brief introduction, immunotherapy response, and fiber

I’m a microbiologist by training and was conducting research with students into the microbiome of drinking water when I was diagnosed with MBC. So when I saw the microbiome session at SABCS, I was super excited.   

 

My introduction to the microbiome and cancer was at an American Society for Microbiology meeting, when I attended a talk on the effects of the gut microbiome on treatment response in melanoma (likely by Dr. Wargo, but I can’t confirm). It’s a fascinating and crucial piece to understanding not only cancer treatment response, but likely in development and metastasis. But I’m a microbiologist, so I’m biased. 

 

 Before we get into the presentations, let’s talk definitions. The microbiome is all the microbes (bacteria, fungi, viruses, protists) living in and on the body (or a specific body part/region) plus all their genetic material. When we talk about just the community of microorganisms themselves, that’s known as the “microbiota”. 

 

And microbiota are everywhere in and on us! From your skin to your mouth to your gut (mostly large intestine) and even in breast tissue and tumors. 

 

How can these microbes affect tumor cells, especially from as far away as the gut? One way would be the effect of chemicals (metabolites)  produced by the microbiota that can be absorbed into the blood and circulated throughout the body, reaching pretty much anywhere. These metabolites can then be sensed by cells causing changes in the cells themselves. A second way could be direct microbial “seeding” from the gut- where microbes travel from the gut to the tumor itself. However, most of the work seems to point to the effects of the gut microbiota on the immune system- which we know plays a pivotal role in cancer development, metastasis, and even response to treatments. Fun fact- the gut is awash not only in the microbiota but immune cells and nerves. That gut feeling? It could be your gut microbiota. 

 

Ok so on to the talks! My favorites were the fungi talk by Dr. Stephen Shiao (discussed in Part 2), and the great overview and role of fiber in the microbiome and treatment response by Dr. Jennifer Wargo. 

 

Let’s dig in starting with Dr. Wargo’s presentation, where she asked the question “could microbiome targeting be the next pillar of cancer care?”. She included this with such things as surgery, radiotherapy, and cytotoxic chemotherapy (among others). Clearly she finds the evidence convincing. 

Let’s look at some of it. First we know that the microbiota found in the gut vary from person to person, both in the specific groups of microbes that are there (composition) and the number of different kinds (diversity). We also know that cancer patients respond differently to treatments- could these be correlative or even causative at some level? Research on the efficacy of immunotherapy in melanoma patients shows that both diversity and composition correlate with response to immunotherapy, and higher diversity leads to better response in mice models. Additionally, transplanting fecal microbiota from a melanoma patient who responds to immunotherapy into a mouse model of melanoma increases survival of the mouse, decreases tumor size, and increases immunity, when compared to mice implanted with fecal matter from non-responders. But what if we did these types of transplants in humans? Dr. Wargo highlighted two clinical trials in pancreatic (trial # NCT04729322) and metastatic colorectal cancer (trial # NCT04729322) doing just that. 

 

Besides transplanting fecal matter from one human to another (as above and as has recently been approved by the FDA for treatment of Clostridium difficile infections, which can be deadly), are there other ways we can shift the microbiome? Yes! Diet, exercise, antibiotics, and even air pollution are known to change the gut microbiome. 

  

(Spencer et al., 2021)

 

Dr. Wargo and others have studied the effects of diet and other lifestyle factors on cancer treatment. One finding in a small number of melanoma patients showed that intake of fiber (in the form of fruits, vegetables and whole grains) over 20g per day was associated with better response to immune checkpoint therapy (see figure to the left). Fiber selects for and against certain bacteria in the gut, and  is converted by the gut microbiome into metabolites known as short chain fatty acids (SCFAs), which are an important signal molecule for the immune system. 

 

This study also used mice fed high and low fiber diets and found similar results in terms of immunotherapy response, but were additioanlly able to study immune response in the tumor where they found increased levels of specific immune cells and signaling. 

 

Dr. Wargo now has a clinical trial, the Diet and Effects Immune Trial (DIET) to see if these preliminary findings hold up in a larger, controlled cohort. They are preparing whole foods, high fiber (50 grams per day) diets and sending them out to trial patients who have melanoma and are being treated with an anti-PD1. Will this lead to longer survival? Very preliminary results are encouraging, and hopefully we will find out at a future oncology conference! 

Dr. Wargo ended her presentation with a suggestion that we need to “embrace a more holistic approach to cancer treatment”. 100% Dr. Wargo!

In my next post, I’ll talk about Dr. Shiao’s research on the effects of the microbiome on breast tumor response to radiation.