Probiotic normalization of Candida albicans in schizophrenia: A randomized, placebo-controlled, longitudinal pilot study

Abstract

The molecules and pathways of the gut-brain axis represent new targets for developing methods to diagnose and treat psychiatric disorders. Manipulation of the gut microbiome with probiotics may be a therapeutic strategy with the potential to relieve gastrointestinal (GI) comorbidities and improve psychiatric symptoms. Candida albicans and Saccharomyces cerevisiae, commensal yeast species, can be imbalanced in the unhealthy human microbiome, and these fungal exposures were previously found elevated in schizophrenia. In a longitudinal, double-blind, placebo-controlled, pilot investigation of 56 outpatients with schizophrenia, we examined the impact of probiotic treatment on yeast antibody levels, and the relationship between treatment and antibody levels on bowel discomfort and psychiatric symptoms. We found that probiotic treatment significantly reduced C. albicans antibodies over the 14-week study period in males, but not in females. Antibody levels of S. cerevisiae were not altered in either treatment group. The highest levels of bowel discomfort over time occurred in C. albicans-seropositive males receiving the placebo. We observed trends towards improvement in positive psychiatric symptoms in males treated with probiotics who were seronegative for C. albicans. Results from this pilot study hint at an association of C. albicans seropositivity with worse positive psychiatric symptoms, which was confirmed in a larger cohort of 384 males with schizophrenia. In conclusion, the administration of probiotics may help normalize C. albicans antibody levels and C. albicans-associated gut discomfort in many male individuals. Studies with larger sample sizes are warranted to address the role of probiotics in correcting C. albicans-associated psychiatric symptoms.

Keywords: Autism; Fungus; Gastroenterology; Infection; Mental health; Sex differences.

Figure 1. Reduction of C. albicans IgG antibodies and improvement of bowel difficulty in males receiving probiotics

Panel A: Males with schizophrenia had significantly lower C. albicans antibody levels following a 14-week regimen of probiotics (n=22) compared to those receiving placebo (n=15). T_start refers to study start and T_end refers to study end. Repeated measures ANOVA (RmANOVA) showed significantly reduced antibody levels associated with the probiotic treatment group over time. ^ap≤0.001 refers to the p-value including all individuals; ^bp≤0.0002 refers to the p-value with the elevated outlier removed. Panel B: Males receiving the placebo who were C. albicans seropositive reported the most bowel difficulties over the 14-week study. C.a.+ refers to C. albicans seropositive; C.a.− refers to C. albicans seronegative. W in the x axis refers to study week. Error bars designate standard errors of the mean for each group at each time point.

Figure 2. C. albicans seropositivity is associated with higher positive psychiatric symptoms on PANSS

Panel A: Trends toward elevated positive PANSS symptom scores over time were observed in C. albicans seropositive (C.a. +) individuals in the pilot probiotic study. C.a.− refers to C. albicans seronegative. W in the x axis refers to study week. Error bars designate standard errors of the mean for each group at each time point. Panel B: Significantly worse psychiatric symptoms in males with C. albicans seropositivity compared to seronegative males were confirmed in an analysis of PANSS scores in the main Sheppard Pratt schizophrenia cohort. Shown are differences in total PANSS scores and in positive symptom subset scores; similarly significant differences related to seropositivity in males were observed for general PANSS scores (not shown). No differences between groups were observed for negative PANSS scores or for females for any of the PANSS comparisons.