Advances In Natural Medicines, Nutraceuticals & Neurocognition

Biography

Biography: Deanna L. Kelly

Abstract

Background: Emerging research suggests that disruptions of the normal flora in the gut microbiota may affect brain development and function and play a role in psychiatric disorders. Butyrate is one of the three major short chain fatty acids (SCFA) that are produced by bacterial fermentation in the gut and plays a critical role in maintaining the integrity of the gut/blood barrier and in several aspects of brain development, including cognitive function. People with schizophrenia are characterized by marked cognitive impairments and currently no known treatments are available to improve cognitive performance. In this study, we examined the effects of oligosaccharide-enriched inulin treatment (OEI, Prebiotin®), a prebiotic that is taken up by the gut bacteria to produce butyrate, on psychiatric symptoms and cognitive changes.

Methods: In this 2-week open-label pilot study, we enrolled participants with a DSM-5 diagnosis of schizophrenia or schizoaffective disorder, between the ages of 18-64 years, and who were hospitalized for at least 7 days, were treated with an antipsychotic without dose changes in the last 14 days and had no antibiotic, prebiotic or anti-inflammatory treatments within the last 3 months. All participants received 2 weeks of OEI (4 grams three times daily) with standard inpatient meals. We measured butyrate levels at baseline and end of study both pre- and post-dose (2 hour) of OEI and food (i.e., pre- and post-prandial). Psychiatric symptoms were evaluated with the Brief Psychiatric Rating Scale (BPRS), the Schedule for Assessment of Negative Symptoms (SANS), the Clinical Global Impression Scale (CGI), and the MATRICS Consensus Cognitive Battery (MCCB). We also collected stool samples nearest baseline and endpoint. Descriptive statistics are included for other variables due to the small sample size and only changes >15% are noted. Changes in butyrate levels were evaluated using Cohen’s D effect size measurements for pre- to post-changes at baseline and endpoint

Results: We enrolled five participants: all of whom were taking olanzapine or clozapine and smoked cigarettes. Three of the five participants were female and four of five were African-American. The mean age of illness onset was 18.8 ± 7.0 years and mean age at the time of study was 38.1 ± 8.5 years.  We observed a 28% increase in the MCCB composite score over the 2 weeks of the study; in particular, there was a 28% increase in visual learning, a 31% increase in processing speed and a 16% increase in attention performance.  On the BPRS, we observed a 15% decrease in psychosis and a 23% decrease in hostility symptoms. We observed little to no change in SANS total score or on other BPRS symptom dimensions. Only 3 participants had baseline and endpoint pre- and post-prandial butyrate levels and stool samples. In the absence of OEI treatment, there was essentially no change in serum butyrate levels pre- to post-prandial (change in serum butyrate = -0.95 μg/ml (0.87% decrease). In contrast, after two weeks of OEI treatment, the pre- to post-prandial change in serum butyrate levels was 25.3 μg/ml, a 24.0% increase (Effect size= 1.32). Microbiome data shows that OEI treatment caused a change in the microbiome diversity, associated with increased relative abundances of known butyrate producing bacteria, such as Bifidobacteria, Roseburia and Coproccus. Side effects were negligible.

Conclusion:Based on our preliminary results, OEI treatment in people with schizophrenia has a promising therapeutic potential. Future studies should replicate these initial findings and OEI may be an effective treatment for cognitive dysfunction. We are currently conducting an NCCIH funded R61/33 clinical trial to examine the effects of OEI on butyrate in a double blind randomized clinical trial.

Funding Source:  This study was funded by the Department of Psychiatry, University of Maryland (UMB) School of Medicine, UMB School of Pharmacy and Institute for Genome Sciences. Prebiotin® was provided by Jackson GI Medical.