Q&A: Gut microbiome may support patient response to immune checkpoint inhibitor treatment
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Research suggests the gut microbiome plays a role in response to cancer immunotherapy, according to a study published in Nature Medicine.
The composition of the gut microbiome previously has been associated with clinical response to immune checkpoint inhibitor (ICI) treatment, but there is limited consensus on the specific link between the microbiome and clinical benefits.
Using shotgun metagenomic sequencing, researchers evaluated stool samples from 165 ICI-naive patients with advanced cutaneous melanoma prior to ICI initiation, as well as 147 metagenomic samples from previous studies.
Results yielded a “relevant, but cohort-dependent” link between the gut microbiome and response to ICI treatment. Machine learning analyses confirmed this link with overall response rates and progression-free survival.
“This study shows the chances of survival based on healthy microbes nearly doubled between subgroups. The ultimate goal is to identify which specific features of the microbiome are directly influencing the clinical benefits of immunotherapy to exploit these features in new personalized approaches to support cancer immunotherapy,” Tim D. Spector, study author and professor of genetic epidemiology at King’s College London, said in a related press release. “But in the meantime, this study highlights the potential impact of good diet and gut health on chances of survival in patients undergoing immunotherapy”
Study author Karla A. Lee, MD, MSc, clinical research fellow at King’s College London and PhD candidate, spoke with Healio about the results of the study and the implications on patient care.
Healio: Why did your team undertake this investigation?
Lee: Despite a number of high-quality published studies investigating the gut microbiome and response to immune checkpoint inhibition, there is a marked lack of consistency of results between studies. Each study has identified somewhat different microbes as being significant players in determining whether patients with a number of malignancies (mainly melanoma, renal carcinoma and non-small cell lung cancer) would respond to immunotherapy. We wanted to delve deeper into this with a large, new cohort and perform meta-analysis on existing publicly available datasets to produce the largest study to date.
Healio: What is the most important take-home message?
Lee: This study confirms that the gut microbiome holds the potential to support treatment of patients receiving ICIs but highlights that this is more complex than previously thought.
Healio: What is the exact correlation between the gut microbiome and ICI response among patients with cancer?
Lee: This is a good question! In short, there is no valid consensus on the exact correlation yet and different groups have found quite different results across different cohorts of patients.
In this study we used a machine learning analysis to confirm the link between the microbiome and overall response rates and progression-free survival for patients treated with ICI, but we also revealed limited reproducibility of microbiome-based signatures across cohorts. We did find that a panel of species, including Bifidobacterium pseudocatenulatum, Roseburia spp. and Akkermansia muciniphila were associated with responders, but no single species could be regarded as a fully consistent biomarker across studies.
Healio: How do these results inform care for patients with advanced melanoma going forward?
Lee: These results highlight the importance of a healthy gut microbiome. While there is still some uncertainty on exactly what a healthy gut microbiome in the context of advanced melanoma looks like, studies in other areas of human health and disease can be extrapolated.
Broadly, diversity of diet and consumption of a wide variety of plant-based foods has been shown to be important in supporting optimal gut health. Patients should aim for a “whole-foods” diet, avoiding processed foods, high quantities of animal meat and artificial flavors and preservatives. Antibiotics have extremely important roles in many clinical settings, particularly in oncology where they can be lifesaving, but, where possible, their use should be minimized, particularly in the month or so leading up to immunotherapy treatment.
Healio: What additional research, if any, is needed?
Lee: Future research is certainly needed. This study demonstrates the complexities of microbiome science in human health and disease and highlights the real need for much larger sample sizes in future observational studies. There are very many factors that impact the composition of the gut microbiome and sample size is critical in allowing us to build statistical models that can take these factors into account.
Smaller clinical studies examining use of fecal microbiota transfers are underway in a number of cancer centers and understanding the results of these will be crucial to furthering our knowledge.
Healio: Is there anything else you would like our readers to know?
Lee: While it might seem tempting for patients to take probiotic supplements to improve their gut health, there are no studies supporting use of probiotics in the context of immunotherapy, and early research from the U.S. has suggested that probiotics may even reduce the chance of response to treatment.
Further work is needed but, in the meantime, patients should optimize their gut health through a high-quality, diverse, whole-foods diet rather than through the consumption of commercial probiotics.
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