The gut-brain axis in bipolar disorder and schizophrenia – a target for precision psychiatry?

Background
Currently available pharmacotherapy for bipolar disorder (BD) and schizophrenia (SCZ) leave ample room for improvement. Evidence is accumulating that the immune system is more activated in patients with BD and SCZ, or at least in a subgroup of these patients. Abnormal immune responses have been reported in patients with BD, of varying disease stages and medication status3. Recent investigations have pointed to the gut-brain axis as a new venue for treatment, with increased inflammation stemming from leaky gut to further affect brain functioning in a significant subset of patients1,2. In a novel double blind randomized controlled trial, we will trans-dimensionally examine the effect of additional treatment with the probiotic product Ecologic Barrier (Winclove Probiotics, Amsterdam, the Netherlands) on psychiatric symptom improvement in 145 patients with BD or a psychotic disorder (GUTS RCT).
Aim
A state-of-the-art overview of available literature will be given on gut-brain functioning in BD and SCZ, including potential targets for future individualized treatment.
Methods
Literature review
Results
To date, multiple studies demonstrate food antigens to be increased in patients with BD and SCZ, compared to HC, which is related to an increased chance for rehospitalization4. Additionally, microbiological antigens were found to be increased in BD and SCZ patients as well, and an association with increased number of suicide attempts was described5. Also, significant microbiome disturbances have been described in BD and SCZ6. Finally, probiotic treatment was found to decrease rehospitalizations following mania in a recent RCT7 and may have beneficial effects on cognitive funcioning8.
Conclusion
Probiotics are promising candidates to improve BD patients’ symptomatology and functioning and there are rational methods to personalize its application with accessible and tolerable predictive biomarkers2.
To further unravel the effects of probiotic treatment in these severe mental disorders and to allow future prediction of treatment, the GUTS RCT will be extended with measures of the intestinal microbiome, intestinal inflammation and intestinal permeability to predict the clinical effect of the probiotic product: calprotectin, microbiome in feces and lipopolysaccharides (LPS) binding protein (LBP) in serum.