What the Evidence Says About Probiotics and Cancer Immunotherapy
By Jyothirmai Gubili, MS, Stacie Corcoran, RN, MS, and Shelly Latte-Naor, MD
Growing evidence suggests that the gut microbiome, a diverse and complex mix of microorganisms and their metabolites, is closely linked to the immune system (https://doi.org/10.1038/nature18847), and researchers are studying whether modulating the gut microbiome affects cancer immunotherapy treatment outcomes. In particular, probiotics—which are flora typically obtained through dietary sources such as yogurt and fermented foods or via supplemental forms—are gaining prominence as a potential strategy to modulate the gut microbiome during cancer treatment.
Cancer Immunotherapy, Dietary Factors, and the Gut Microbiome
Patients’ gut microbiota may have an important role in the efficacy of checkpoint inhibitor therapy. In three groundbreaking studies of patients (https://doi.org/10.1126/science.aao3290) with melanoma (https://doi.org/10.1126/science.aan4236), lung, and kidney cancers (https://doi.org/10.1126/science.aan3706), profiling of oral, gut, and fecal samples revealed significant differences in the diversity and composition of microbial populations between responders and nonresponders to checkpoint inhibitor therapy. Furthermore, when tumor-bearing mice were colonized with feces from responders, the mice responded more favorably to immunotherapy compared to feces from nonresponders.
The findings suggest that modifying the gut microbiome may improve patients’ response to immunotherapy. However, analyzing its complex communities of microorganisms can be challenging: Despite similar colonization experiments, those studies did not reach a consensus about the specific microbial species responsible for the observed benefits. The authors concluded that Faecalibacterium prausnitzii and members of the Ruminococcaceae family (https://doi.org/10.1126/science.aan4236), Akkermansia muciniphila (https://doi.org/10.1126/science.aan3706), or several other species including Bifidobacteria (https://doi.org/10.1126/science.aao3290) were beneficial, but more research is needed to determine what constitutes a healthy gut microbiome and the mechanisms through which it influences immune responses.
What the Research Reveals
Whether dietary approaches can alter the microbial constitution to a favorable immune state is currently being investigated. Preliminary findings show utility of oral probiotics (https://doi.org/10.1093/annonc/mdu106) in oncology settings (https://doi.org/10.3390/nu13041160), but researchers conducting a large systematic review found substantial bias across a majority of analyzed studies (https://doi.org/10.3390/curroncol28060435), citing a need for well-designed trials.
Other studies report conflicting results. Researchers in one study found that gut colonization is not always achieved (https://doi.org/10.1016/j.cell.2018.08.041) despite supplementation with probiotics, and another that examined post-antibiotic recovery actually associated probiotics with a delay (https://doi.org/10.1016/j.cell.2018.08.047) in gut-microbiome reconstitution.
However, the evidence supports fecal microbiota transplantation for recurrent Clostridium dificile infection (https://doi.org/10.1056/NEJMoa1205037), and current guidelines (https://doi.org/10.1093/cid/ciy149) from the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America recommend it as the treatment for those infections.
A secondary contributor to the gut microbiota are prebiotic resistant starches, which are fermentable but indigestible fibers that are degraded by gut bacteria such as Faecalibacterium prausnitzii and Eubacterium rectale to yield butyrate and other short-chain fatty acids that may induce immunity and promote colonic health (https://doi.org/10.1038/ismej.2014.63) in the host. Unmodified potato starch was shown to stimulate the production of short-chain fatty acids (https://doi.org/10.1128/mBio.02566-18) in a study of healthy adults. Clinical trials are investigating the potential benefits of that compound in patients undergoing immunotherapy (https://clinicaltrials.gov/ct2/show/NCT04552418) and stem cell transplantation (https://clinicaltrials.gov/ct2/show/NCT02763033).
Probiotic supplements are generally considered safe, but early data from an observational study suggested that indiscriminate use of commercially available probiotic supplements may be harmful (https://doi.org/10.1126/science.aaz7015) in the setting of immune checkpoint inhibitors.
What Oncology Nurses Need to Know
Accumulating evidence suggests that probiotics can have a positive impact on health by inducing favorable changes in gut bacteria. However, more research is needed to guide the therapeutic use of probiotics.
Oncology nurses assess and address a variety of lifestyle behaviors, including nutrition, across a patient’s cancer care trajectory. They educate patients on healthy dietary practices to reduce their risk for certain cancers and minimize or mitigate treatment-related issues such as digestive and taste alterations. As evidence emerges regarding probiotics and immunotherapy efficacy, oncology nurses must be knowledgeable and prepared to share this information with patients, including the possible harms associated with commercial probiotic supplements in the context of immunotherapy and the benefits of a high–prebiotic fiber diet without contraindications.