Prebiotic Treatment in People with Schizophrenia

PROJECT SUMMARY
People with schizophrenia have a broad range of cognitive impairments, which are major determinants of the
poor functional outcome observed in people with this disorder. Unfortunately, pharmacological and non-
pharmacological interventions have limited benefits for these impairments. In the absence of effective
treatments, cognitive impairments remain a critical unmet therapeutic need, and the development of novel
approaches for their treatment remains a central therapeutic challenge. Over the past 10 years, considerable
evidence has emerged to suggest that the gut microbiota has significant effects on brain development and
behavior, in part, through the regulation of immune system function. The gut microbiota affects immune system
function through the production of short chain fatty acids (SCFAs) and other mechanisms. There are three
major SCFAs: butyrate, propionate, and acetate, of which, butyrate appears to have the most pronounced
effects on the immune system. Prebiotics are dietary fibers that promote the growth or activity of gut
microorganisms, which leads to enhanced well-being of the host; they have been shown to increase the activity
of multiple different bacteria species, including butyrate-producing bacteria. In light of the emerging evidence
that suggests schizophrenia is characterized by multiple abnormalities of the immune system, which lead to a
pro-inflammatory state, the proposed R61 and R33 projects are designed to evaluate the hypothesis that
prebiotic administration will lead to increased production of butyrate, through increased activity of butyrate-
producing bacteria in the gut microbiota; the increase in serum butyrate levels will be associated with changes
in cognitive function, symptoms, and metabolic measures. In the R61 project, we will conduct a 10-day,
double-blind, placebo-controlled, randomized clinical trial (RCT) to determine if the prebiotic: Prebiotin
(12g/day), an oligofructose-enriched inulin (FOS), alters the hypothesized biological signature, i.e., increases
serum butyrate levels. We will use an inulin-challenge paradigm to asses the effect of FOS on serum butyrate
levels. In the R33 project, we will conduct a 12-week, double-blind, placebo-controlled, RCT, to confirm the
ability of the prebiotic: FOS (12g/day), to alter the hypothesized biological signature: serum butyrate levels. We
will also examine the extent to which changes in serum butyrate levels are associated with changes in
cognitive function, symptoms, and metabolic measures. We will use the MATRICS Consensus Cognitive
Battery to assess change in cognitive function. The study will provide critical preliminary data on the clinical
utility of prebiotic treatment for the improvement of cognitive function in people with schizophrenia.

Grant Number: 3R33AT009990-05S1
NIH Institute/Center: NIH
Principal Investigator: ROBERT BUCHANAN