The gut-immune-brain interactome and microbial dysbiosis in psychiatric disorders

Abstract

Risk factors for psychiatric disorders (inflammation, food sensitivity, Toxoplasma gondii exposure, endothelial barrier defects) are part of biological pathways that are operant in the body’s largest immune organ, the gastrointestinal (GI) tract. Central to GI function is a homeostatic microbial community. In updated analyses of our case-control psychiatric cohort, we present data regarding gut dysbiosis in psychiatric disorders and discuss its applicability to brain processes. We found significant elevations of two well-documented markers of bacterial translocation, soluble CD14 (sCD14) and lipopolysaccharide binding protein (LBP), in schizophrenia ( n = 267) vs. controls ( n = 281, p 0.0001). sCD14 but not LBP levels were also elevated in mania ( n = 95) vs. controls ( p 0.0001). In schizophrenia, LBP was strongly associated with endocrine disturbances ( p 0.0001) and sCD14 with GI symptoms ( p 0.01). The presence of bacterial DNA in blood plasma was then examined in 247 samples by 16S rRNA amplification and sequencing. In preliminary analyses, gut-related bacteria from the phylum Firmicutes was documented in 6% of the samples, with possible case-control differences in those that were positive for bacterial translocation. Activation of the complement pathway coincided with bacterial DNA measures ( p 0.007 ), supporting our clinical and experimental animal models linking gut-related psychiatric risk factors to immune factors such as complement components that function in synaptic plasticity. Ongoing discoveries of novel gut-brain physiological pathways advocate consideration of GI-corrective measures as adjunctive treatments of complex brain disorders.