The effect of prebiotics on the gut microbiota in patients treated with atypical antipsychotics: a pilot study
E. J. Giltay, N. J. de Bles, N. Rius-Ottenheim, J. P. BogersIntroduction
Atypical antipsychotic (AAP) drugs are prescribed to patients with psychotic and other mental disorders. A common adverse effect is metabolic syndrome (MetS), often via weight gain and dyslipidemia. Besides lifestyle factors, drug-induced gut dysbiosis has been proposed as a mechanism. Dysbiosis is often marked by reduced Bifidobacterium , yet its causal role in MetS remains unclear.
Objectives
Our aim was to evaluate the relative change in the proportion of bifidobacteria within the total fecal bacterial community, with the hypothesis that supplementation would lead to an increase.
Methods
We included psychiatric patients with BMI > 25 kg/m², using long-term atypical antipsychotics in a pilot study. Following a 4-week run-in period, participants received a daily dose of the prebiotic combination of galacto-oligosaccharides (GOS) and 2’-fucosyllactose (2’-FL) (7.0 g Biotis® GOS + 0.7 g 2’-FL) for 6 weeks, with a washout of 4 weeks thereafter. The primary outcome was change in fecal bifidobacteria. Secondary outcomes included mental health (e.g., EQ-5D utility score) and metabolic syndrome measures. Fecal microbiome composition was assessed by 16S rRNA gene sequencing of the V4 region on the Illumina NovaSeq6000 platform.
Results
Twenty-one participants using AAP (clozapine; n=9) were included (mean age 43.4 years; 67% male); of whom 76% had a psychotic disorder. Gut microbiome composition shifted from baseline to week 4, with stability thereafter.
Faecalibacterium
increased significantly (p=0.03) during supplementation, while diversity indices remained unchanged.
Bifidobacterium
increased non-significantly (p=0.10) during supplementation, but the overall increase from baseline to week 10 was statistically significant (change = 0.098; SE = 0.030; p = 0.002). This may be explained by the possibility that some participants may have unintentionally started their prebiotics already during the run-in phase. No serious adverse events occurred. Metabolic assessments (BMI, WHR, RR) did not change during supplementation. Subjective scales showed slight favorable changes, but none reached statistical significance, except for the EQ-5D utility score (QoL), which improved significantly (p = 0.01).
Image 1: Long description.