Although psychiatric disorders demonstrate substantial clinical heterogeneity and high comorbidity, the underlying biological mechanisms remain elusive. The microbiota–gut–brain axis (MGBA) has been highlighted and suspected as an important cross-system perspective for elucidating the pathophysiology of major psychiatric disorders.
A series of studies called “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.
Thus far, 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 findings revealed coordinated changes linking gut microbes, brain networks and symptoms—supporting the development of AI-assisted diagnosis and personalized therapies.
The studies within the BIGHI heve revealed:
(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.
The study group plans to expand the BIGHI into a collaborative network and promote data harmonization and interdisciplinary collaboration to advance computational psychiatry as well as its clinical translation.
Early Findings
Early findings of the study suggest that certain features observed in electroencephalography may serve as non-invasive biomarkers indicating the severity of the disease and possible treatment response. Neuroimaging investigations also revealed widespread alterations in the brain network structure across different psychiatric conditions. When trained on the MRI data, machine learning models demonstrated high accuracy in distinguishing schizophrenia patients from healthy individuals
The Role of Gut Bacteria
Distinct changes in gut bacteria within the cohort were observed. “Patients with psychiatric disorders showed a decrease in beneficial short-chain fatty acid-producing bacteria and an increase in pro-inflammatory microbes. Notably, these microbial shifts were linked to the severity of the symptoms, oxidative stress, and cognitive performance, highlighting the relevance of microbiome alterations in psychiatry.”
A significant contributions of the study shows an integration of the brain and gut data sets, which helped uncover the underlying mechanisms of various disorders. When the patients were grouped using combined brain and gut data, the brain-derived profiles were more closely related to symptom severity, while gut-based profiles showed stronger links to cognitive performance. Researchers found that differences in gut bacteria were linked to changes in brain functions. The combined analysis of neuroimaging, microbiome, and blood biomarkers also revealed accelerated biological aging in patients with schizophrenia, supporting the growing view that psychiatric disorders can affect multiple body systems rather than only the brain.
Next Steps
The researchers believe that expanding the BIGHI initiative may enable the development of reliable diagnostic tools, microbiome-based therapies, neuromodulation strategies, and AI-driven strategies for managing psychiatric disorders. By providing compelling insights into the microbiota-gut-brain axis in psychiatric disorders, the initiative supports advances in biomarker-driven diagnosis and personalized treatment strategies—paving the way for a better mental healthcare.
Source: Wu, F., et al. (2026). The Brain–Gut Health Initiative (BIGHI): A Prospective Cohort on Psychiatric Disorders in China. Research. DOI: 10.34133/research.1142. https://spj.science.org/doi/10.34133/research.1142