Stress Testing of the Gut–Brain Axis for Precision Medicine in Functional Dyspepsia

Functional dyspepsia is heterogeneous in mechanism, yet treatment is still chosen largely by trial and error. Physiological tests and microbiome profiling each capture one part of the gut–brain axis, and none predicts treatment response on its own. We propose a framework that tests the axis under controlled demand. A standardised meal challenges the gut-to-brain limb, and sham-controlled transcutaneous auricular vagus nerve stimulation challenges the brain-to-gut limb. The responses define five candidate coordinates. Three describe overall reactivity, engagement of the auriculo-vagal arc, and acute modulation by stimulation. A fourth, the Neural–Peripheral Dominance Index, contrasts trait psychological loading with acute peripheral reactivity. A fifth, the Substrate Index, describes the baseline composition of the stool microbiome. None of the coordinates is validated. We specify how each is computed and standardised, and we outline a two-phase strategy to test them. Phase 1 assesses feasibility, test–retest reliability, and structural predictions in patients with postprandial distress syndrome. Phase 2 tests whether the Dominance Index modifies the relative benefit of vagal stimulation and a dietary intervention. We also state in advance the results that would lead us to revise or abandon the framework.