Analysis of Gut Microbiota in Patients with Exacerbated Symptoms of Schizophrenia following Therapy with Amisulpride: A Pilot Study

Abstract

Evidence is mounting that the gut microbiome is related to the underlying pathogenesis of schizophrenia. However, effects of amisulpride on gut microbiota are poorly defined. This study was aimed at analyzing cytokines and fecal microbiota in patients with exacerbated symptoms of schizophrenia treated with amisulpride during four weeks of their hospital stay. In the present study, feces collected from patients with schizophrenia were analyzed using 16S rRNA pyrosequencing and bioinformatic analyses to ascertain gut microbiome composition and fasting peripheral blood cytokines. We found that patients undergoing treatment of schizophrenia with amisulpride had distinct changes in gut microbial composition at the genus level, increased levels of short-chain fatty acid-producing bacteria (Dorea and Butyricicoccus), and reduced levels of pathogenic bacteria (Actinomyces and Porphyromonas), but the level of Desulfovibrio was still high. We also found a significant downregulation of butanoate metabolism based on functional analysis of the microbiome. After treatment, elevated levels of interleukin- (IL-) 4 and decreased levels of IL-6 were found. Our findings extend prior work and suggest a possible pharmacological mechanism of amisulpride treatment for schizophrenia, which acts via mediation of the gut microbiome.

Psycho-pharmacomicrobiomics: a systematic review and meta-analysis

“…A total of 19 studies met the inclusion criteria (see PRISMA flowchart, Figure 1). Of these, 14 were longitudinal studies that reported data on pre-and post treatment differences in gut microbiome across 484 patients treated with either antidepressants (six studies [21][22][23][24][25][26]; N=167) or antipsychotics (eight studies [27][28][29][30][31][32][33][34]; N=317); Five studies reported cross-sectional data on gut microbiome features in patients treated with antipsychotics (N=182) vs antipsychotic-free patients (N=165) [27,[35][36][37][38] and two on patients treated with antidepressants vs antidepressants-free patients [26,38,39]. No studies directly investigated mood stabilizers.…”

“…Longitudinal studies Of the eight longitudinal studies involving antipsychotics, three investigated Risperidone [27,31,32], one Amisulpiride [33], one Olanzapine [30], two Quetiapine [28,29], and one a variety of different antipsychotics [34]. Five studies reported data on gut microbiome alpha diversity before and after treatment with antipsychotics [28,30,32,33,38]. All studies reported the Shannon index as a measure of alpha diversity.…”

“…None of the studies included in the quantitative synthesis on alpha diversity included children, reported analysable data on gender, none used polypharmacy, and all used the same sequencing method, follow-up timing ranged from 1 to 6 months. Four longitudinal studies reported data on beta diversity before and after treatment with antipsychotics [28,30,33,38]. When individual data from these studies were pooled no significant difference was found in beta-diversity before vs after treatment (F=0.38; R 2 =0.01; P=0.68; eFigure1).…”

“…Three studies reported data on microbiome functional analysis following treatment with antipsychotics [28,30,33]. Two of out three studies reported significant changes across 12 different microbiome functional pathways, including those involved in the metabolisms of short-chain free fatty acids [28,33] (see eTable 1).…”

Reviewing the Potential Therapeutic Approaches Targeting the Modulation of Gastrointestinal Microflora in Schizophrenia

“…In a pilot study, Zheng et al [49] aimed to analyze the consequences of amisulpride (400-1200 mg/kg) treatment for four weeks by applying biochemical and molecular biology protocols. As observed in the case of all atypical antipsychotics (AAP), it caused an increase in the levels of the short-chain fatty acid (SCFAs)-producing bacteria Dorea and Butyricicoccus and of those that are potentially pathogenic, such as Actinomyces and Porphyromonas with persistence at a high ratio of Desulfovibrio.…”