Circulating propionate and butyrate are associated with metabolic improvements following probiotic and dietary fiber supplementation in patients on antipsychotics: a post-hoc analysis of a randomized controlled trial

Second-generation antipsychotics, a cornerstone of psychiatric disorder management, render treated patients highly prone to metabolic abnormalities. To address this unmet clinical need, this post-hoc analysis drew on data from a previous trial to examine the correlations between plasma short-chain fatty acid (SCFA) level alterations and metabolic changes in the context of probiotic-fiber intervention. In this trial, individuals diagnosed with schizophrenia or bipolar disorder, who were undergoing stable atypical antipsychotic therapy, were recruited for this study. They were subsequently randomized in a 1:1:1:1 ratio to four treatment groups: combined probiotics (1680 mg/d) and dietary fiber (60 g/d); probiotics (1680 mg/d) with dietary fiber placebo; dietary fiber (60 g/d) with probiotics placebo; and double placebo (probiotics placebo plus dietary fiber placebo). Assessments were conducted at screening/baseline, week 4, and week 12, and the measurement of circulating SCFAs was performed via liquid chromatography-mass spectrometry. The analysis, employing the last-observation-carried-forward method, encompassed 79 participants who provided at least one follow-up plasma sample for the quantification of SCFAs. The 12-week combined administration of probiotics and dietary fiber was associated with changes in circulating levels of SCFAs and improvements in metabolic indices. More importantly, the higher levels of propionate were associated with decreased weight (adjusted odds ratio [OR]: 0.61 per quartile increase, 95% confidence interval [CI]: 0.38–0.96) and homeostatic model assessment of insulin resistance (HOMA-IR) (adjusted OR:0.58, 95% CI: 0.36–0.94). Also, the higher levels of butyrate were associated with a 42% lower odds (adjusted OR: 0.58, 95%CI:0.36–0.93) of elevated body mass index (BMI) and a 49% lower odds (adjusted OR: 0.51, 95%CI:0.31–0.86) of elevated insulin levels. The findings of this study suggested that elevated circulating levels of butyrate and propionate might be associated with reduced weight gain and improved insulin resistance in individuals receiving antipsychotic medications. ClinicalTrials.gov NCT03379597, trial registration date: 11/29/2017. Overall Recruitment Status: completed.