Prebiotic Treatment in People With Schizophrenia - Pilot Study
Condition: Schizophrenia; Schizoaffective Disorder
MeSH terms: Schizophrenia; Psychotic Disorders
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to examine changes in serum butyrate levels with the prebiotic:
      Prebiotin (12g/day), an oligofructose-enriched inulin (OEI); the effect of OEI on the
      composition of the gastrointestinal microbiota in people with schizophrenia; and the
      relationship of the composition of the gut microbiota to various clinical, cognitive, and
      neuroimaging variables.
    

Detailed description: 
      Over the past 10 years, considerable evidence has emerged from animal studies to suggest that
      the gut microbiome has significant effects on brain development and behavior, with
      bidirectional communication between the enteric nervous system, gut and the central nervous
      system (CNS) (Diaz Heijtz et al, 2011; Douglas-Escobar et al, 2013; Dinan et al, 2014). The
      gut microbiota have been shown to: a) produce multiple neurotransmitters, including
      gamma-aminobutyric acid (GABA), dopamine, norepinepherine, and serotonin, and may regulate
      CNS levels of these neurotransmitters; b) modulate brain development through the regulation
      of synaptogenesis; and c) modulate the levels of stress hormones during brain development,
      which may affect stress response and anxiety behavior (Diaz Heijtz et al, 2011; Dinan et al,
      2014; Sudo et al, 2004; O'Mahony et al, 2015). Moreover, the gut microbiota effects the
      production of neurotrophins, including brain-derived neurotrophic factor (BDNF), which plays
      a significant role in neurogenesis and synaptic plasticity (Sudo et al, 2004; Nemani et al,
      2015).

      The gut microbiome may also affect brain development and function through its regulation of
      immune system function, which is mediated, in part, through the production of short-chain
      fatty acids (SCFA). There are three major SCFAs: butyrate, propionate, and acetate. Butyrate
      is of particular interest, since it plays a key role in maintaining gut homeostasis and
      epithelial integrity: butyrate is the primary energy source for intestinal colonocytes; and,
      of the three SCFAs, butyrate appears to have the most pronounced effects on immune system
      function and may exert its effects directly through immune pathways and indirectly through
      the maintenance of the integrity of the intestinal-blood barrier (Hamer et al, 2008; Louis et
      al, 2010; Brahe et al, 2013; Vital et al, 2014). The intestinal-blood barrier restricts the
      entrance of toxins, pathogens and antigens into the blood circulation; thus, increased
      permeability could lead to the entrance of substances and subsequent immune response.

      The multiple effects of the gut microbiome on brain development and behavior, suggest that
      alterations in the gut microbiome may occur in schizophrenia and play a part in the
      pathophysiology of the disorder. The increased prevalence of gastrointestinal disorders in
      schizophrenia; the association of infections, including infections with Toxoplasma gondii,
      which can induce intestinal inflammation, with the risk for the development of schizophrenia;
      and evidence of increased gut permeability provide further indirect evidence for disruption
      of the gut microbiome in this disorder (Dinan et al, 2014; Nemani et al, 2015; Severance et
      al, 2012; Severance et al, 2014). Although a number of studies have been conducted in other
      neuropsychiatric disorders, including autism (Parracho et al, 2005; Tomova et al, 2015),
      which demonstrate altered bacterial composition of the gut microbiome, there is only one
      published study of the microbiome in schizophrenia. Yolken and colleagues examined the
      oropharyngeal microbiome in people with schizophrenia, and found that there were increased
      levels of the bacteriophage, Lactobacillus phage phiadh, genome in the schizophrenia group,
      which were correlated with co-occurring immunological disorders (Yolken et al, 2015). There
      is one published study of gut microbiota in schizophrenia. Shen and colleagues found a
      significant reduction in butyrate producers in people with schizophrenia compared to healthy
      controls (Shen et al. Schiz Res, https://doi.org/10.1016/j.schres.2018.01.002).

      The purpose of this study is to examine changes in serum butyrate levels with the prebiotic:
      Prebiotin (12g/day), an oligofructose-enriched inulin (OEI); the effect of OEI on the
      composition of the gastrointestinal microbiota in people with schizophrenia; and the
      relationship of the composition of the gut microbiota to various clinical, cognitive, and
      neuroimaging variables.
    

Intervention name(s): Prebiotin; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Prebiotin (12g/day), an oligofructose-enriched inulin (OEI); placebo-OEI
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Other