Dietary Fiber Lacks a Consistent Effect on Immune Checkpoint Blockade Efficacy Across Diverse Murine Tumor Models

Area of Science:

• Oncology
• Immunology
• Microbiome Research

Background:

• Immune checkpoint blockade (ICB) is a key cancer therapy, but its efficacy is limited.
• Dietary fiber's role in enhancing ICB via the microbiome is suggested, but prior studies had confounding dietary variables.
• The impact of isolated fiber versus complex diets on ICB needs clarification.

Purpose of the Study:

• To investigate the effect of dietary fiber quantity and type on gut microbiome, metabolome, and ICB efficacy in mouse cancer models.
• To differentiate the effects of fiber from other dietary components in grain-based versus purified diets.
• To assess the consistency and robustness of fiber's impact on anti-PD-1 therapy.

Main Methods:

• Mice were fed grain-based chow or purified diets with varying levels of isolated fibers (cellulose, inulin).
• Gut microbiome composition and metabolite levels were analyzed.
• ICB efficacy (anti-PD-1) was evaluated across multiple tumor models.

Main Results:

• Diet type (chow vs. purified) significantly impacted the gut microbiome and metabolome more than fiber content.
• Dietary fiber had a weaker and inconsistent effect on ICB efficacy than previously reported.
• No tested model showed a clear pattern supporting fiber as the primary driver of ICB efficacy.

Conclusions:

• Dietary fiber appears to have limited or inconsistent effects on ICB efficacy in mouse models.
• Other dietary factors, potentially correlated with fiber intake, may be responsible for observed clinical benefits of high-fiber diets.
• Findings may necessitate re-evaluation of dietary recommendations for patients undergoing immunotherapy.