Bugs and Drugs
How the gut microbiome impacts response to cancer immunotherapy
The importance of the gut microbiome for maintaining health or driving disease has been a hot research topic over the last few years, with numerous publications revealing the role of certain gut bacteria in disease risk, development, and progression. In the field of oncology, we have learned that certain bacteria can dramatically impact patients’ response to treatment and the risk of side effects. This is particularly relevant for some of the newer cancer drugs known as immunotherapies.
Immunotherapies work by taking the brakes off the body’s immune system, which allows it to work more effectively. Most of these treatments are antibodies that block the activity of PD-1 or PD-L1. Interestingly, recent research has started to uncover the importance of the gut microbiome in modulating response to these therapies. One study found that in patients with melanoma, those who responded to PD-L1 therapy had higher levels of Bifidobacterium longum, Collinsella aerofaciens, and Enterococcus faecium. When fecal samples from these responders were transferred to mice, the authors saw enhanced response to treatment and slower tumor growth. Similarly, when fecal transplants were given from melanoma patients who previously responded to PD-1 therapy to patients who had progressed through this treatment, 6/15 patients started to respond to treatment with a reduction in tumor size or long-term disease stabilization. Despite this being very exciting and promising, fecal transplants are not currently recommended because their long-term safety and efficacy is still under investigation.
Several studies have demonstrated the importance of overall bacterial diversity and response to immunotherapy. In patients with non-small cell lung cancer undergoing treatment with nivolumab, higher diversity was related to longer progression-free survival and a greater likelihood of responding to treatment. This was also true for melanoma patients undergoing anti PD-1/PD-L1 treatment. In these melanoma patients, a higher consumption of fruit, vegetables, and whole grains was linked to the presence of bacteria that improved treatment response from previous studies. In addition, a recent meta-analysis showed that using antibiotics prior to or during immunotherapy treatment, which dramatically reduces bacterial diversity, may reduce efficacy and ultimately patient survival.
Using dietary interventions is currently one of the safest ways to impact the gut microbiome and overall bacterial diversity. This can also be easily implemented by most patients who are receiving immunotherapy. Prebiotic fibers such as oligosaccharides, fructans, and galactans can increase the production of short chain fatty acids and support the growth of potentially beneficial bacteria such as Bifidobacteria. Other foods and certain supplements may also encourage favourable shifts in the gut microbiome and enhance immune function. Naturopathic doctors with additional training in cancer care can help formulate a diet for you that encompasses these potentially beneficial foods.
Research Synthesis and Take-Home Messages:
The gut microbiome plays an important role in improving response to immunotherapy
Supporting bacterial diversity in the microbiome seems to be the safest approach to enhancing immunotherapies until we understand more. This can be done by eating an array of healthy prebiotic foods and fibers. Speak to your naturopathic doctor how to incorporate these fibers and other foods that may positively impact the gut microbiome and the immune system!
Avoiding antibiotics before and during immunotherapy treatment is prudent, but antibiotics should not be withheld when they are clinically necessary.
Fecal transplants hold promise for shifting the gut microbiome and enhancing response to immunotherapy, but this intervention is still highly experimental and has serious risks, so is not recommended outside of supervised clinical studies at this time
Dr. Sarah Soles, MSc, ND
Dr. Soles is one of our naturopathic physicians with a special interest in cancer care. She is a Fellow of the American Board of Naturopathic Oncology and a senior research assistant with the Knowledge in Naturopathic Oncology Website.
Integrated Health Clinic
Clinic number: 604-888-8325
www.integratedhealthclinic.com
References:
- Davar D, Dzutsev AK, McCulloch JA, et al. Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients. Science. 2021 Feb 5;371(6529):595-602.
- Jin Y, Dong H, Xia L, et al. The Diversity of Gut Microbiome is Associated With Favorable Responses to Anti-Programmed Death 1 Immunotherapy in Chinese Patients With NSCLC. J Thorac Oncol. 2019 Aug;14(8):1378-1389.
- Matson V, Fessler J, Bao R, et al. The commensal microbiome is associated with anti–PD-1 efficacy in metastatic melanoma patients. Science. 2018;359(6371):104-108.
- Petrelli F, Iaculli A, Signorelli D, et al. Survival of Patients Treated with Antibiotics and Immunotherapy for Cancer: A Systematic Review and Meta-Analysis. J Clin Med. 2020 May 13;9(5):1458.
- Russo E, Nannini G, Dinu M, Pagliai G, Sofi F, Amedei A. Exploring the food-gut axis in immunotherapy response of cancer patients. World J Gastroenterol. 2020;26(33):4919-4932.
- Spencer CN, Gopalakrishnan V, McQuade J, et al. The gut microbiome (GM) and immunotherapy response are influenced by host lifestyle factors [abstract]. Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. Cancer Res.2019;79: Abstract 2838.
