Consumption of High Fiber and Its Improved Immunotherapy Responses in Melanoma Patients

According to an international research collaboration, melanoma patients who receive medication that makes it easier for their immune system to attack cancer cells respond better to medical treatment when their diet intake has high fiber.

According to new research from the MD Anderson Cancer Center at the University of Texas, patients with melanoma who reported eating a high-fiber diet when starting immunotherapy survived longer without cancer development than patients who ate enough fiber.

The results of the study have been published in the journal Science.

This benefit is most noticeable in patients who do not take commercially available probiotic supplements.  Parallel clinical trials supported the observational findings.

"Research by our team and others shows that intestinal microbiota affect the response to immunotherapy, but the role of diet and probiotic supplements has not been well studied," said co-author Jennifer Wargo, MD, professor of genomic medicine and surgical oncology. “Our study highlights the potential consequences of the patient's diet and supplementation when starting treatment with an immunoassay.  These results further support clinical trials of microbial modification aimed at improving the cancer effect using diet and other strategies.”

Patients who reported consuming more fruits, vegetables, legumes and whole grains reached the study limit for adequate fiber intake.  Thirty-seven patients with adequate fiber intake improved (did not reach average) compared with 91 patients with adequate fiber intake (average 13 months).  Every five grams increase in daily fiber intake is associated with a 30 percent lower risk of cancer progression or death.

When patients were further grouped according to a high or low fiber diet and commercially available probiotic supplement use, 18 of the 22 patients (82 percent) were found to respond to immunotherapy, with insufficient fiber intake and no probiotic use.  Of the 101 patients, 60 (59 percent) reported inadequate fiber intake or probiotic use.  The answer is defined as complete or partial complete or partial tumor contraction or persistent disease for at least six months.  Probiotic use alone is not associated with significant differences in improvement survival or reactions to immunotherapy.

"Dietary fiber is important for gut health, which is important for overall health, and the two things are very closely intertwined," said co-senior author Gary Daniel-McDougall, Ph.D., associate professor of epidemiology.  "In this study, we found that dietary fiber is also important for the treatment of cancer, which brings us to a point where design studies are designed to answer the questions that patients really want to answer: 'Is it important that I eat now and that it affects my treatment outcome?' We have come together to find answers for our patients. '

Differences in intestinal microbiota and preclinical models

The study began by analyzing the intestinal microbiota profile of 438 melanoma patients, 321 of whom were diagnosed with the disease late and treated with systemic treatment, and 293 of them had an evaluable response to follow-up treatment.  The vast majority (87 percent) of these patients received immunohistochemical blockade, usually with PD-1 inhibitors.  A total of 158 patients also completed a lifestyle study on the use of antibiotics and probiotics;  Of these, 128 completed the dietary questionnaire when the immunoassay started treatment.

The research team reinforced their earlier findings that well-known and potentially beneficial bacteria involved in the digestion of fiber or starch - showed high levels of Ruminococcus and Foxybacterium brownsitzi in patients who responded to immunotherapy.  Contrary to previous findings, the overall diversity of intestinal bacteria was not correlated with the response to immunotherapy, which may be due to the large size of this patient cohort.

The researchers tested high- and low-fiber diets and probiotic use in several advanced melanoma models to shed light on the possible mechanisms behind observational findings from patient associates.  In many models, probiotic use is associated with immune test blockade, large tumors, low intestinal microbial diversity, and poor response to low cytotoxic D cells in the tumor microenvironment.  A high-fiber diet is associated with slower tumor growth and significantly higher frequency of CD4 T cells in pre-clinical samples treated with PD-1 inhibitors.

References: 

1. “Dietary Fiber Improves Outcomes for Melanoma Patients on Immunotherapy.” ScienceDaily, 23 Dec. 2021, https://www.sciencedaily.com/releases/2021/12/211223143050.htm.

“Dietary Fiber and Probiotics Influence the Gut Microbiome and Melanoma immunotherapy response” Science.org, Christine N. Spencer, Jennifer L. McQuade, Vancheswaran Gopalakrishnan, John A. McCulloch, Marie Vetizou, Alexandria P. Cogdill, Md A. Wadud Khan, Xiaotao Zhang, Michael G. White, Christine B. Peterson, Matthew C. Wong, Golnaz Morad, Theresa Rodgers, Jonathan H. Badger, Beth A. Helmink, Miles C. Andrews, Richard R. Rodrigues, Andrey Morgun, Young S. Kim, Jason Roszik, Kristi L. Hoffman, Jiali Zheng, Yifan Zhou, Yusra B. Medik, Laura M. Kahn, Sarah Johnson, Courtney W. Hudgens, Khalida Wani, Pierre-Olivier Gaudreau, Angela L. Harris, Mohamed A. Jamal, Erez N. Baruch, Eva Perez-Guijarro, Chi-Ping Day, Glenn Merlino, Barbara Pazdrak, Brooke S. Lochmann, Robert A. Szczepaniak-Sloane, Reetakshi Arora, Jaime Anderson, Chrystia M. Zobniw, Eliza Posada, Elizabeth Sirmans, Julie Simon, Lauren E. Haydu, Elizabeth M. Burton, Linghua Wang, Minghao Dang, Karen Clise-Dwyer, Sarah Schneider, Thomas Chapman, Nana-Ama A. S. Anang, Sheila Duncan, Joseph Toker, Jared C. Malke, Isabella C. Glitza, Rodabe N. Amaria, Hussein A. Tawbi, Adi Diab, Michael K. Wong, Sapna P. Patel, Scott E. Woodman, Michael A. Davies, Merrick I. Ross, Jeffrey E. Gershenwald, Jeffrey E. Lee, Patrick Hwu, Vanessa Jensen, Yardena Samuels, Ravid Straussman, Nadim J. Ajami, Kelly C. Nelson, Luigi Nezi, Joseph F. Petrosino, P. Andrew Futreal, Alexander J. Lazar, Jianhua Hu, Robert R. Jenq, Michael T. Tetzlaff, Yan Yan, Wendy S. Garrett, Curtis Huttenhower, Padmanee Sharma, Stephanie S. Watowich, James P. Allison, Lorenzo Cohen, Giorgio Trinchieri, Carrie R. Daniel, Jennifer A. Wargo, 23 Dec. 2021, https://www.science.org/doi/10.1126/science.aaz7015