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Elevated mucosal expression of hypoxia-inducible factor (HIF), which transcriptionally regulates genes associated with gut barrier protection, results in greater levels of butyrate that are essential for sustaining intestinal immunometabolic balance 78

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It is important to clarify that, whereas population-level PRS models require formal effect-size modeling, linkage disequilibrium correction, ancestry calibration, and validation across large cohorts, the score used in this workflow is a functional polygenic score (PRS-F) designed for mechanistic, individual-level interpretation rather than for epidemiological prediction

Research frequently cites 0.5% as an effective sweet spot, balancing meaningful results against low irritation risk