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

This is the authors' abstract. We don't add key points for this paper.

Functional dyspepsia and related disorders of gut–brain interaction are still managed without mechanism-based stratification, and trials of vagal neuromodulation have rarely measured the microbiome alongside autonomic and symptomatic endpoints. We argue that the obstacle is conceptual rather than technical: what is missing is a framework in which these readouts are coupled, not a new technology. Borrowing the logic of the cardiac stress test, we treat the gut–brain axis as a coupled, bidirectional reactivity system whose functional properties surface only under controlled perturbation. Perturbing the system in both directions yields an individual reactivity profile. Three composite indices capture overall system reactivity, vagal arc engagement, and acute modulation. A fourth coordinate, the Neural–Peripheral Dominance Index, weighs trait neural vulnerability against acute peripheral reactivity, while a fifth, the microbial Substrate Index, fixes the trait-level compositional context of the gut. Autonomic engagement is read out not from any single signal but from a sign-aligned composite of paced-breathing heart rate variability, electrodermal activity, and pupillometry. We position the profile as a mechanistic layer beneath Rome IV classification, meant to explain the heterogeneity that persists within symptom-defined subtypes, and we outline a two-phase strategy for testing mechanism-aligned therapeutic responses prospectively.