The gut microbiome, which are the microorganisms and their genes found in the human body’s intestinal tract, may influence the therapeutic response to immune checkpoint blockade (ICB) cancer treatment [Routy et al., 2018; Matson et al., 2018; Gopalakrishnan et al., 2018; Frankel et al., 2017; Peters et al., 2019; Andrews et al., 2021 as cited in reference i]. What is more, factors such as diet and medication use may impact the gut microbiome [Wu et al., 2011; McDonald et al., 2018; Maier et al., 2018; Suez et al., 2018; Willing et al., 2011; Asnicar et al., 2021 as cited in reference i]. In the below study, the authors explore how dietary fiber intake and probiotic use influence the microbiome and immunotherapy response in individuals with melanoma.
This study included 438 individuals with melanoma. Most of the individuals were receiving ICB, anti-programmed cell death 1 (anti-PD-1) therapy for metastatic melanoma. Participants were classified as responders to treatment (complete or partial response or stable disease for 6 months or more) or non-responders (stable disease for less than 6 months or progressive disease). The authors profiled participants’ gut (fecal) microbiome. Participants receiving ICB treatment completed the National Cancer Institute Dietary Screener Questionnaire, including questions on dietary fiber intake. Fiber intake was considered per 5 grams per day increments and in 2 cohorts, with low or insufficient defined as less than 20 grams per day and sufficiently high defined as 20 grams or more per day. Participants also answered questions on probiotic use. Lastly, the authors designed preclinical models in mice, investigating fiber intake, probiotic use, microbiota composition, and response to treatment.
The authors found:
- A significantly higher abundance of Ruminococcaceau in the gut microbiota of responders to treatment compared to non-responders. No significant difference in the overall composition of the gut microbiota of responders compared to non-responders
- 31% of participants had taken a probiotic supplement within the past month. No significant difference in progression-free survival (PFS) or treatment response in those taking probiotics compared to those not taking probiotics
- Those with sufficient dietary fiber intake had improved PFS compared to those with insufficient dietary fiber intake. With every 5 gram increase in daily dietary fiber intake, there was a 30% lower risk of disease progression or death, with similar associations found for dietary fiber intake and ICB response
- No significant difference in the composition of the gut microbiota in those with sufficient compared to insufficient dietary fiber intake
- Significantly longer PFS in those with sufficient dietary fiber intake and no probiotic use, with similar associations found for ICB response. There was more microbial diversity in those with sufficient dietary fiber intake and no probiotic use, although not statistically significant
- In preclinical models, mice receiving probiotics had an impaired response to treatment and significantly larger tumors compared to control mice
- In preclinical models, mice receiving a fiber-rich diet had delayed tumor outgrowth compared to mice receiving a fiber-poor diet when treated with anti-PD-1. This effect was not seen in germ-free mice, suggesting that the dietary intervention and treatment response was microbiota dependent
For the Patient and Caregiver
For increased dietary fiber intake, consider how many servings of fruits, vegetables, legumes, whole grains, and nuts and seeds you eat each day. Look for opportunities to increase these types of foods, such as adding spinach to an omelet, berries to yogurt, having a quinoa bowl with chickpeas and your favorite dressing for lunch, and mixed nuts as a snack more often than processed foods lower in fiber such as chips or cookies. Some foods highest in fiber include split peas, raspberries, green peas, barley, broccoli, and chia seeds.
For the Healthcare Team
It may be beneficial to encourage dietary fiber intake for patients receiving ICB. For example, encourage a nutritious eating pattern with high consumption of fruits, vegetables, legumes, whole grains, and nuts and seeds. More research is indicated to understand the timing of this intake–if there is a positive benefit on treatment response if an individual previously had low fiber intake but increases fiber intake during treatment. Further research is also needed to understand probiotic supplementation recommendations for patients receiving ICB, and how food sources of probiotics such as kimchi or yogurt may have an impact on the microbiota and treatment response.
For more information on the gut microbiota, take a look at this Science Nook on plant-based eating.
[i] Spencer CD, McQuade JL, Gopalakrishnan V, McCulloch JA, Vetizou M, Cogdill AP…Wargo JA (2021). Dietary fiber and probiotics influence on the gut microbiome and melanoma immunotherapy response. Science 374, 1632-1640. https://www.science.org/doi/10.1126/science.aaz7015