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Test a high-fibre diet as an immunotherapy adjunct

People who eat more fibre appear to respond better to immunotherapy, while some probiotic supplements may do the opposite. A proper trial would settle it.

Observational data in melanoma associate higher dietary fibre intake with improved checkpoint response, and over-the-counter probiotic use with worse response, with supporting mouse experiments. Diet is a cheap, scalable and modifiable exposure but has never been tested randomly alongside checkpoint therapy with microbiome and immune endpoints. Adherence measurement, through stool short-chain fatty acids, makes a rigorous trial possible.

Hypothesis
A supervised high-fibre dietary intervention during checkpoint therapy improves response rate compared with usual diet, with stool short-chain fatty acid levels mediating the effect.
Rationale
Fibre fermentation produces short-chain fatty acids that alter T-cell differentiation, giving a plausible mechanism, and the observational effect size reported in melanoma was large. The intervention has no toxicity and independent health benefits.
What would test it
A randomised trial of provided high-fibre meals versus usual diet in patients starting checkpoint blockade, with objective response as primary endpoint and stool metabolomics and metagenomics as mechanistic endpoints.
Maturity
early clinical
Who has to act
research
Cost to try
Medium ($1M to $50M)
Years to first evidence
5
Bottlenecks it attacks

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