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Major psychiatric disorders are characterized by substantial clinical heterogeneity and high comorbidity, yet their underlying biological mechanisms are not fully uncovered. The microbiota-gut-brain axis (MGBA) offers a cross-system perspective for elucidating the pathophysiology of major psychiatric disorders. The Brain-Gut Health Initiative (BIGHI) was established as the first prospective longitudinal cohort in China dedicated to investigating major psychiatric disorders guided by the framework of MGBA, enabling large-scale, transdiagnostic, and longitudinal analyses of brain-gut interactions. To date, the BIGHI has enrolled over 1,200 participants with schizophrenia, major depressive disorder, bipolar disorder, and healthy controls, with multidimensional data collected including clinical symptomatology, neurocognitive performance, electroencephalography, magnetic resonance imaging, peripheral blood biomarkers, and gut microbiome profiles. The studies within the BIGHI reveal (a) brain-gut physiological alterations in psychiatric disorders; (b) systematic relationships among brain function, peripheral physiological markers, and gut microbiome; and (c) brain-gut network patterns with marked interindividual heterogeneity. In future studies, we will expand the BIGHI into a collaborative network and promote data harmonization and interdisciplinary collaboration to advance computational psychiatry as well as its clinical translation.