Research Update – January 2021

Russo, E., Nannini, G., Diny, M., et al.
Exploring the food-gut axis in immunotherapy response of cancer patients
World Journal of Gastroenterology (2020).  26(33): 4919-4932

Abstract

Nowadays, immunotherapy is widely used to treat different cancer types as it boosts the body’s natural defenses against the malignancy, with lower risk of adverse events compared to the traditional treatments. The immune system is able to control cancer growth but, unfortunately, many cancers take advantage of immune checkpoints pathways for the immune evasion. An intricate network of factors including tumour, host and environmental variables influence the individual response to immune checkpoints’ inhibitors. Between them, the gut microbiota (GM) has recently gained increasing attention because of its emerging role as a modulator of the immune response. Several studies analyzed the diversities between immunotherapy-sensitive and immunotherapy-resistant cohorts, evidencing that particular GM profiles were closely associated to treatment effect. In addition, other data documented that interventional GM modulation could effectively enhance efficacy and relieve resistance during immunotherapy treatment. Diet represents one of the major GM determinants, and ongoing studies are examining the role of the food-gut axis in immunotherapy treatment. Here, we review recent studies that described how variations of the GM affects patient’s responsiveness to anti-cancer immunotherapy and how diet-related factors impact on the GM modulation in cancer, outlining potential future clinical directions of these recent findings.

InspireHealth’s Interpretation

The focus of this research review was to summarize the research exploring the relationship between diet, the gut microbiome, and patients’ responses to newer immunotherapies.

Immunotherapies are being used with increasing frequency and have significantly improved prognosis, often with fewer side effects, for patients with more advanced cancers. Checkpoint inhibitors (CPI) are a class of immunotherapy currently in use.  Healthy cells display proteins on their surfaces that can bind with other proteins (called checkpoint proteins) on the surface of immune cells called T cells. Once bound, the T cells know not to attack the healthy cell. Unfortunately, some cancer cells also have these same proteins on their cell surfaces so the immune system is tricked into thinking that the cancer cell is a healthy cell and therefore doesn’t destroy it. CPIs disrupt this binding so that the immune system can effectively identify and attack cancer cells.  While some people respond very well to immunotherapies, some do not. Although many factors are involved in treatment responsiveness, the gut microbiota or microbiome is gaining attention as an important factor in CPI and immune responsiveness.

The gut microbiome is the collection of microorganisms (bacteria, viruses, protozoa, and fungi) that live in the gastrointestinal (digestive) tract, and interest in its role in health and immunity has exploded in recent years. Researchers have noted particular differences in the composition of the gut microbiome between immunotherapy sensitive patients (responders) and immunotherapy resistant patients (non-responders). Understanding how diet can alter the microbiome (for the better or worse), and how the microbiome can influence the immune system is the focus of this research paper.

Interestingly, diet can have both direct and indirect effects on cancer prevention, prognosis and treatment response. Healthy, mostly plant-based diets are associated with a large diversity of gut microbial species often including beneficial Lactobacilli and Bifidobacterium. Such diets provide significant fibre and antioxidant compounds which can directly inhibit cancer growth, and through the microbiome, they can positively influence anti-tumour immune responses (an indirect effect).  In fact, the microbial species found in healthier microbiomes also produce nutrients which can improve immune T cell function and reduce inflammation, both of which are important for effective cancer treatment.

By contrast, large amounts of simple sugars, salt, alcohol metabolites, saturated and trans fatty acids found in diets high in refined cereals, sugar-sweetened beverages, alcohol, and red and processed meat (so-called Western diets), seem to foster the growth of fewer species with a preponderance of less beneficial Bacteroides species. Western diets are associated with negative immune and cancer effects by increasing inflammation, promoting cancer cell growth and reducing cancer cell death.

Not surprisingly, the gut microbiomes of CPI responders are similar to those who follow a whole foods diet, whereas the non-responders’ microbiomes resemble those of Western dieters. Mouse model studies have also shown beneficial (cancer fighting) interactions between specific microbiomes and CPIs, suggesting that the efficacy of CPIs could be improved through microbiome modulation.  When researchers transplant fecal microbiota from human CPI responders and non-responders into mice with cancer being treated with a CPI, the responses of the mice will parallel those of the humans.

One might wonder if it wouldn’t be easier to take a good probiotic supplement.  However, probiotic trials have produced mixed results.  These authors state that a probiotic supplement may be a “double-edged sword” as serious blood infections with probiotic use may occur, especially in those who are immune compromised.  However, cancer treatment trials using probiotics are ongoing and probiotics may be helpful for some.  In the meantime, fostering a diverse range of healthy microbes is possible with eating a mostly plant-based diet and minimizing sugary and processed foods as well as alcohol.

While this paper focused on the interaction of the diet, microbiome and immunotherapy, there is no reason to believe that a mostly plant-based diet wouldn’t also benefit other more traditional cancer therapies. The links between a healthy diet, a healthy microbiome, and enhanced immunity are rapidly gaining evidence.