A new randomized controlled feeding trial aims to investigate how a high-fiber diet may impact the gut microbiome and immune response in melanoma patients receiving immunotherapy. The Diet and Immune Effects Trial (DIET) is currently enrolling patients at The University of Texas MD Anderson Cancer Center in Houston, Texas.
Published in November 2024 in BMC Cancer, this phase II study protocol describes plans to enroll 45 melanoma patients starting standard-of-care immune checkpoint blockade therapy. Patients will be randomized 2:1 to receive either a high-fiber dietary intervention (targeting 50 g fiber per day from whole foods) or a healthy control diet (20 g fiber per day) for up to 11 weeks.
The trial is supported by funding from several foundations, including the Elkins Foundation, Seerave Foundation, Rising Tide Foundation, and the Mark Foundation for Cancer Research. Additional support comes from MD Anderson's Melanoma SPORE program, Physician Scientist Program, and Moonshot Program.
Recent research has highlighted the potential role of the gut microbiome in modulating response to cancer immunotherapy. Preclinical studies and small human trials have shown that altering the microbiome, such as through fecal microbiota transplant, may enhance immunotherapy efficacy in some patients. However, fecal transplant faces numerous logistical and safety challenges for widespread implementation.
Diet is known to be a key determinant of gut microbial composition. The DIET study aims to evaluate whether dietary modification alone, specifically a high-fiber intervention, can beneficially alter the microbiome and potentially impact immunotherapy outcomes in melanoma patients.
The trial will enroll patients in three cohorts: those receiving neoadjuvant immunotherapy prior to surgery (n=12), those receiving adjuvant therapy after surgery (n=21), and those with unresectable metastatic disease (n=12). Key eligibility criteria include age 18 or older, body mass index 18.5-40 kg/m2, ECOG performance status 0-1, and willingness to adhere to the provided diet. Patients with ongoing colitis, history of severe immunotherapy-related colitis, active inflammatory bowel disease, or recent antibiotic use are excluded.
In this double-blind study, all meals, snacks and energy-containing beverages will be provided to participants for the duration of the intervention. Diets in both arms are isocaloric and macronutrient-controlled, designed by registered dietitians to meet individual caloric needs. The control diet reflects average fiber intake in melanoma patients and the general US population.
The primary objective is to evaluate changes in gut microbiome composition and function. Stool samples will be collected longitudinally for microbiome sequencing and metabolomic analysis. Secondary objectives include assessing changes in systemic and tumor immunity, metabolic profiles, quality of life, and clinical outcomes like response rate and progression-free survival.
This represents the first controlled feeding study conducted in cancer patients actively receiving immunotherapy. The rigorous dietary control aims to minimize confounding variations in eating behaviors that impact other nutrition intervention studies. The 11-week intervention duration also exceeds that of many prior controlled feeding trials.
By providing all meals and collecting detailed compliance data, the researchers hope to achieve high adherence to the dietary intervention. Previous observational studies by this group found that melanoma patients reporting higher habitual fiber intake had improved immunotherapy responses. The current trial will test whether a controlled high-fiber intervention can induce beneficial changes to the microbiome and immunity.
Key strengths of the study design include the randomized controlled nature, comprehensive biospecimen collection, and rich clinical data capture. Limitations include the relatively small sample size of 45 patients, which is not powered for clinical outcome comparisons between arms. The single-center design at a major academic cancer center may also limit generalizability.
The investigators conclude that this study will provide critical data on the feasibility and biological effects of a high-fiber dietary intervention in melanoma patients receiving immunotherapy. They hypothesize that modulating the microbiome through diet could potentially impact systemic and anti-tumor immunity.
If successful, this proof-of-principle study could inform larger trials powered for clinical outcomes. Ultimately, dietary modification could represent a safe, scalable approach to enhance immunotherapy efficacy. The rich biospecimen collection may also yield insights into mechanisms linking diet, the microbiome, and anti-tumor immunity.
However, the authors caution that clinical benefit remains to be demonstrated. Even if microbial and immune changes are observed, it is unknown whether these will translate to improved outcomes. The heterogeneity of melanoma and variability in immunotherapy response adds complexity to interpreting results.
Nonetheless, this novel controlled feeding study in cancer patients represents an important step in rigorously evaluating the impact of diet on the microbiome and immunity during cancer therapy. The results will help inform nutritional strategies for patients receiving immunotherapy and guide future research into diet, microbiome and cancer.
For clinicians, this study highlights the potential importance of diet and lifestyle factors in modulating immunotherapy response. While results are pending, encouraging patients to follow a healthy diet rich in plant-based foods aligns with general cancer prevention guidelines. The feasibility data may also provide insights into practical considerations for implementing dietary interventions in cancer patients.
As the field of immunotherapy continues to evolve, understanding how modifiable factors like diet impact treatment efficacy could open new avenues to optimize outcomes. This study exemplifies the type of rigorous nutritional science needed to establish evidence-based dietary guidelines for cancer patients in the era of immunotherapy.
References
Farias RM, Jiang Y, Levy EJ, et al. Diet and Immune Effects Trial (DIET)- a randomized, double-blinded dietary intervention study in patients with melanoma receiving immunotherapy. BMC Cancer. 2024;24(1):1493. Published 2024 Dec 4. doi:10.1186/s12885-024-13234-1
