Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response.

Abstract

Gut bacteria modulate the response to immune checkpoint blockade (ICB) treatment in cancer, but the effect of diet and supplements on this interaction is not well studied. We assessed fecal microbiota profiles, dietary habits, and commercially available probiotic supplement use in melanoma patients and performed parallel preclinical studies. Higher dietary fiber was associated with significantly improved progression-free survival in 128 patients on ICB, with the most pronounced benefit observed in patients with sufficient dietary fiber intake and no probiotic use. Findings were recapitulated in preclinical models, which demonstrated impaired treatment response to anti–programmed cell death 1 (anti–PD-1)–based therapy in mice receiving a low-fiber diet or probiotics, with a lower frequency of interferon-γ–positive cytotoxic T cells in the tumor microenvironment. Together, these data have clinical implications for patients receiving ICB for cancer.

• Authors: 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
• Journal: Science (New York, N.Y.) (Science) Vol. 374 Issue 6575 Pg. 1632-1640 (Dec 24 2021) ISSN: 1095-9203 [Electronic] United States
• PMID: 34941392 (Publication Type: Journal Article, Observational Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Dietary Fiber
• Fatty Acids, Volatile
• Immune Checkpoint Inhibitors

Topics

• Animals
• Cohort Studies
• Dietary Fiber
• Fatty Acids, Volatile (analysis)
• Fecal Microbiota Transplantation
• Feces (chemistry, microbiology)
• Female
• Gastrointestinal Microbiome
• Humans
• Immune Checkpoint Inhibitors (therapeutic use)
• Immunotherapy
• Male
• Melanoma (immunology, microbiology, therapy)
• Melanoma, Experimental (immunology, microbiology, therapy)
• Mice
• Mice, Inbred C57BL
• Probiotics
• Progression-Free Survival
• T-Lymphocytes