Elevated risk for new-onset psychiatric disorders in vulnerable populations harboring gut-brain axis dysfunction in a large US study of medical records

Abstract

Disruptions of the gut microbiome in psychiatric disorders are increasingly linked to sub-clinical inflammation, weakened blood-gut/blood-brain barriers and an overall gut environment conducive to the development of autoimmunity. Our studies of serum/plasma biomarkers indicate that gut-brain axis dysfunction is triggered by infection or exposure to pathogens, dysbiotic commensals, dietary antigens or autoantigens, and that these triggers are quantifiable. Subsequent exposures to culprit antigens may then perpetuate this gut-brain axis dysfunction in the form of psychiatric symptoms and neuropathologies over the course of one's lifetime.Here we follow-up our laboratory-based biomarker projects with large-scale queries of the TriNetX electronic health networks database, a longitudinal cohort of over 200 million anonymized patients. Psychiatric, non-psychiatric, microbiome-, diet-, immune-related and other comparison groups were identified and highly matched for demographic, socioeconomic and clinical variables using propensity score analyses. Other health conditions (obesity, hypertension, diabetes, asthma, stroke, smoking, alcohol) and neurological disorders (autism, multiple sclerosis, Alzheimer's Disease) were evaluated as covariates and low probability control outcomes.Fungal diagnoses were associated with (1) new-onset mental health diagnoses in populations thought to be particularly vulnerable (individuals with existing mood disorders, pregnant women, adolescent girls, the LGBTQ community) and (2) gastrointestinal (GI) conditions (gastroesophageal reflux disease, constipation; ORs 1.88-2.80, p<0.0001). Candidiasis during pregnancy was associated with maternal development of psychosis and depression (ORs 1.5-1.75, p<0.0001-0.005). Certain allergy tests performed during pregnancy (e.g. milk/dairy targets) were associated with the development of mood disorders in mothers (ORs 1.45-1.58, p<0.0001-0.006).These medical record findings in conjunction with our laboratory-based blood biomarker results strongly point to elevated risks for new-onset psychiatric disorders in vulnerable populations harboring GI abnormalities. These data support that the ability of fungi to transform a healthy microbiome into one that is pro-inflammatory makes fungal microorganisms particularly informative biomarkers to better identify and potentially treat individuals with psychiatric disorders.