Gut Microbiota Markers for Antipsychotics Induced Metabolic Disturbance in Drug Naive Patients with First Episode Schizophrenia _ A 24 Weeks Follow-up Study

BackgroundWhile cardiometabolic adverse effects associated with antipsychotic treatment is an important clinical challenge, the underlying mechanisms are unknown. Here we investigated if changes in gut microbial composition associate with the metabolic disturbance induced by the risperidone treatment of schizophrenia. MethodsNinety-four first episode, drug naive schizophrenia patients (SZ), and 100 healthy controls (HCs) were enrolled at baseline. Six metabolic parameters (glucose, homeostasis model assessment of insulin resistance (HOMA-IR), Total cholesterol (Total-C), Low-density lipoprotein cholesterol (LDL-C), High-density lipoprotein cholesterol (HDL-C) and triglycerides) and body mass index (BMI) were measured for all participants. Gut microbial composition (microbials) was determined by fecal samples using 16S ribosomal RNA sequencing. Both the metabolic parameters and the gut microbiota were analyzed at baseline (all participants) and after 12 and 24 weeks of risperidone treatment (patients). ResultsThe glucose was significantly higher in SZ than HCs at baseline (p = 0.005). After 24-weeks treatment with risperidone, the levels of BMI, glucose, HOMA-IR, Total-C, LDL-C, HDL-C and triglyceride, were significant changed compared to baseline (p < 0.01). Six microbials showed significant changes in abundance after 24 weeks of risperidone treatment in SZ (p < 0.05), and four of these (Bacteroidetes, Proteobacteria, Christensenellaceae, and Enterobacteriaceae) were associated with the changes in metabolic parameters (p < 0.05). At baseline, the abundance of the microbials Christensenellaceae and Enterobacteriaceae were significantly associated with changes in triglyceride, BMI and HOMA-IR after 24-week risperidone treatment. ConclusionsChanges in gut microbial composition induced by risperidone treatment may be a key pathway underlying the metabolic disturbances observed in SZ patients. While these findings warrant replication in independent samples, they provide insight into the role of microbiota in SZ treatment, which can form the basis for development of better SZ treatment strategies.