Probiotic formulation for patients with psychotic or bipolar disorder who have screened positive for increased intestinal permeability

Schizophrenia and bipolar disorder are severe mental disorders, both placing significant burden on global health. In both disorders, patients suffer from a variety of psychotic, depressive and manic symptoms. Additionally, the risk for developing metabolic syndrome and neurocognitive decline is increased in both disorders. Besides the overlap in psychiatric symptomatology, cognitive and biological functioning, there is also a large genetic overlap. Nowadays it is generally assumed that psychotic disorders (including schizophrenia, schizo-affective disorder) and bipolar disorder are disorders that are not entirely separated, but represent different stages of a continuum of clinical pictures.

Although the introduction of antipsychotic medications in the 1950s has substantially improved clinical symptoms of schizophrenia, the disease is still causing considerable morbidity and mortality. In bipolar disorder, lithium is since many years the first-choice maintenance-treatment, with anticonvulsants and antipsychotics as major alternatives. However, up to 50% of patients with bipolar disorder do not respond adequately to these treatments and still suffer from manic and/or depressive episodes, often severely affecting functioning.

Recent investigations have pointed to the gut-brain axis as a new venue for treatment, with increased inflammation stemming from increased intestinal permeability to further affect brain functioning in a significant subset of patients. In multiple studies increased intestinal permeability in schizophrenia and bipolar disorders is demonstrated by translocation of food and bacterial antigens, as well as intestinal microbiome disturbances. This is associated with dysregulation of the immune system, precipitation and exacerbation of psychiatric symptomatology, metabolic complications and increased cognitive impairment. Probiotics are promising candidates to improve patients’ symptomatology and functioning and there are rational methods to personalize its application with accessible and tolerable predictive biomarkers.

We hypothesize that treating patients with intestinal permeability improving probiotics (in addition to usual treatment; antipsychotic / mood stabilizing treatment) will cause a decrease in psychiatric symptoms (measured with the Brief Psychiatric Rating Scale (BPRS)), such as psychotic, depressive and manic symptoms, in patients with psychotic and bipolar disorders with increased intestinal permeability. We also expect improvement of intestinal permeability and inflammation, immune parameters, metabolic syndrome features, cognition, general functioning and gastro-intestinal (GI) complaints in these patients. Additionally, we hypothesize that individual treatment response to intestinal permeability improving probiotics can be predicted by measurement of intestinal permeability, intestinal inflammation, or a combination of these and other immunological, medical or psychiatric factors.

We hypothesize that treating patients with intestinal permeability improving probiotics (in addition to usual treatment; antipsychotic / mood stabilizing treatment) will cause a decrease in psychiatric symptoms (measured with the Brief Psychiatric Rating Scale (BPRS)), such as psychotic, depressive and manic symptoms, in patients with psychotic and bipolar disorders with increased intestinal permeability. We also expect improvement of intestinal permeability and inflammation, immune parameters, metabolic syndrome features, cognition, general functioning and gastro-intestinal (GI) complaints in these patients. Additionally, we hypothesize that individual treatment response to intestinal permeability improving probiotics can be predicted by measurement of intestinal permeability, intestinal inflammation, or a combination of these and other immunological, medical or psychiatric factors.

Primary outcome is psychiatric symptoms severity as assessed with the Brief Psychiatric Rating Scale (BPRS)

Patients screened positive for LBP and other inclusion criteria will enter a 12 week treatment period in which they are randomized 1:1 to either twice daily 2 gram probiotic formulation (Ecologic®Barrier; Bifidobacterium bifidum W23, Bifidobacterium lactis W51, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Lactobacillus brevis W63, Lactobacillus casei W56, Lactobacillus salivarius W24, Lactococcus lactis W19, Lactococcus lactis W58; 1x1010 colony forming units/day) or placebo twice daily. Outcome measurements will be assessed at baseline, half way treatment, end of treatment, and at a follow-up 3 months post-treatment.