Abstract
Preclinical studies have shown that the gut microbiota can play a role in schizophrenia (SCH) pathogenesis via the gut-brain axis. However, its role in the antipsychotic treatment response is unclear. Here, we present a 24-week follow-up study to identify gut microbial biomarkers for SCH diagnosis and treatment response, using a sample of 107 first-episode, drug-naïve SCH patients, and 107 healthy controls (HCs). We collected biological samples at baseline (all participants) and follow-up time points after risperidone treatment (SCH patients). Treatment response was assessed using the Positive and Negative Symptoms Scale total (PANSS-T) score. False discovery rate was used to correct for multiple testing. We found that SCH patients showed lower α-diversity (the Shannon and Simpson’s indices) compared to HCs at baseline (p = 1.21 × 10−9, 1.23 × 10−8, respectively). We also found a significant difference in β-diversity between SCH patients and HCs (p = 0.001). At baseline, using microbes that showed different abundance between patients and controls as predictors, a prediction model can distinguish patients from HCs with an area under the curve (AUC) of 0.867. In SCH patients, after 24 weeks of risperidone treatment, we observed an increase of α-diversity toward the basal level of HCs. At the genus level, we observed decreased abundance of Lachnoclostridium (p = 0.019) and increased abundance Romboutsia (p = 0.067). Moreover, the treatment response in SCH patients was significantly associated with the basal levels of Lachnoclostridium and Romboutsia (p = 0.005 and 0.006, respectively). Our results suggest that SCH patients may present characteristic microbiota, and certain microbiota biomarkers may predict treatment response in this patient population.
Highlights
Schizophrenia (SCH) is a chronic and severe mental disorder, characterized by impaired cognitive functions and social disability [1]
The PERMANOVA based on those four β-diversity dissimilarity metrics shows that the between-group difference was significantly different than the within-group difference, in either SCH patients or healthy controls (HCs) (Supplementary Table 2); Principal Coordinate Analysis (PCoA) based on the four metrics showed a significant separation of the two groups (Supplementary Figure 4A–D)
In the present study, we found a significant relationship between microbial biomarkers and clinical response after 24-week risperidone treatment in the first-episode, drug-naïve SCH patients
Summary
Schizophrenia (SCH) is a chronic and severe mental disorder, characterized by impaired cognitive functions and social disability [1]. The associations between the gut microbial compositions and the risk of SCH have been reported in several psychiatric patient studies [5, 9,10,11,12,13]. Albeit inconsistent associations for specific microbial taxa, these studies indicated that patients with SCH displayed a dysbiosis of gut microbiota. In the 6th-week, five patients did not provide stool samples; five patients did not come to our hospital due to unknown reasons, and one dropped due to hospitalization for poor treatment response. Inflammatory markers, hypersensitive C-reactive protein (hs-CRP), and homocysteine (HCY) (HCYinduced oxidative stress and inflammation via Nox4/NF-κB pathway) [21] have been reported to be associated with SCH [22, 23], we explored the relationship of gut microbiota, inflammatory markers, and treatment response. The gut microbiota and inflammatory biomarkers were measured with the subject’s condition
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