What is the role of dietary fiber and probiotics on the microbiome and melanoma immunotherapy response?
Clinical Applications
Dr. Schwarzenberger is the former physician editor of DermWorld. She interviews the author of a recent study each month.
By Kathryn Schwarzenberger, MD, FAAD, July 1, 2022
In this month’s Clinical Applications column, Physician Editor Kathryn Schwarzenberger, MD, FAAD, talks with Kelly Nelson, MD, FAAD, from MD Anderson Cancer Center, about her recent Science paper “Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response.”
DermWorld: I read with great interest your team’s recent article on the role of dietary fiber and probiotics on the microbiome and melanoma immunotherapy response. Tell us about your study.
That pivotal observation and the mechanistic mouse experiments then led to the next questions: 1) Why are the microbiomes different among responders and non-responders? 2) How can we manipulate the gut microbiome to overcome resistance to ICB therapy?
Jennifer McQuade, MD, assistant professor in the department of melanoma medical oncology, and Carrie Daniel-MacDougal, MD, associate professor in the department of epidemiology, began leading efforts to better understand the environmental exposures (diet, probiotic use, medications, etc.) among melanoma patients receiving ICB therapy. In this study, 438 melanoma patients receiving ICB therapy completed a lifestyle survey — which included information about dietary habits and probiotic and medication use — and provided fecal samples. The patients were followed to assess response to ICB therapy with standard of care radiologic imaging.
Want to read more?
Check out the archives of the most popular Clinical Applications columns.
DermWorld: While I realize summarizing this very comprehensive article for our readers here would be challenging, would you be willing to try to describe the key findings for those who may have not read it yet?
Dr. Nelson: Patients who reported sufficient dietary fiber (>/= 20 g/day) demonstrated improved progression-free survival (PFS) over patients with less than 20g of fiber per day. Every 5-gram increase in daily dietary fiber corresponded to a 30% lower risk of disease progression or death! The interactions between dietary fiber and supplemental probiotic use were then explored. The longest PFS was seen in patients with the highest dietary fiber intake and no probiotic use.
These human observations were then explored by feeding mice a high-fiber versus low-fiber diet, then challenging with melanoma tumors and treating with ICB. Mice receiving the high-fiber diet demonstrated delayed tumor growth compared to mice who received the low-fiber diet. When the same experiment was replicated in germ-free mice, no differences were observed — supporting the hypothesis that the fiber-based diet effects are dependent upon microbes.
DermWorld: Is there any reason to think this response is likely to be melanoma-specific? Do we have data to suggest other cancers respond similarly?
Dr. Nelson: One of the first papers describing the importance of the gut microbiome and cancer was an evaluation of the gut microbiome in patients with AML who received stem cell transplant. Patients with the most diverse gut microbiomes before SCT demonstrated significantly better overall survival than those with the least diversity (Blood. 2014. PMID 24939656). Similar trends with gut microbiome diversity and response to ICB have been shown in renal cell carcinoma, non-small cell lung cancer, and urothelial cancer (PMID 29097494).
DermWorld: What impact did the high-fiber diet alone have on the microbiome of the melanoma patients you studied? Is there any way to know if this microbiome change was the reason for the improved clinical outcome?
Dr. Nelson: The relationships between environmental exposures (including diet, medications, probiotics, fermented foods) are complex and assigning direct causality can be tricky. The research team is exploring the next step in this space through a prospective feeding study where patients are provided with all the food they are supposed to eat for a defined study period. This prospective study will help us better understand the direct relationship of food (and fiber) intake and gut microbiome diversity.
Patient pamphlets
Check out the Academy’s patient pamphlets on melanoma and more.
DermWorld: Could specific gut bacteria ultimately be more beneficial than others?
Dr. Nelson: Yes. Past gut microbiome studies have indicated that specific bacteria are associated with favorable responses to ICB therapy. Clues about the metabolic effects of these more and less beneficial microbes provided clues about the importance of dietary fiber in patients with complete responses to ICB therapy. The power of looking at dietary patterns is the simplicity of subsequent therapeutic interventions: Changing the way you eat is a fairly low-risk and easily adopted intervention, especially when compared to fecal microbiome transplant!
DermWorld: Was Mom right? Should we eat our fruits and vegetables every day?
Dr. Nelson: It’s certainly looking that way. Eating whole foods rich in fiber may have more benefits than previously thought!
One of the most important things for us to know as dermatologists is the interplay of oral antibiotics and ICB therapy. Specifically, that antibiotic exposure around the time of ICB initiation is associated with significantly reduced survival across many tumor types and multiple studies. As dermatologists, it’s important for us to be aware of this association especially when we are asked to manage cutaneous adverse events for cancer patients. Sometimes it’s necessary, but if there are other treatment options, I try to lean away from oral antibiotics.
Kelly Nelson, MD, FAAD, is associate professor at the department of dermatology division of internal medicine at MD Anderson Cancer Center in Houston, and associate medical director in the department of dermatology division of internal medicine at the Melanoma and Skin Center in Houston. Her paper appeared in Science. Dr. Nelson does not have any relevant financial or commercial conflicts of interest.
Disclaimer: The views and opinions expressed in this article do not necessarily reflect those of DermWorld.
