Gut Microbiota Markers for Antipsychotics Induced Metabolic Disturbance in Drug Naïve Patients with First Episode Schizophrenia – a 24-Week Follow-Up Study

Background: While cardiometabolic adverse effects associated with antipsychotic treatment are an important clinical challenge. Here we investigated whether changes in gut microbial composition are associated with the metabolic disturbances induced by risperidone treatment in drug naive, first episode schizophrenia patients. Methods: Ninety-four drug naive, first episode schizophrenia patients (SZ), and 100 healthy controls (HCs) were enrolled. Six metabolic parameters (glucose, HOMA-IR, Total cholesterol (Total-C), LDL-C, HDL-C and triglycerides) and BMI were measured for all participants. Gut microbial composition was determined based on fecal samples using 16S ribosomal RNA sequencing. Both metabolic parameters and gut microbiota were analyzed at baseline (for all participants) and after 12 and 24 weeks of risperidone treatment (for patients only). Results: Serum glucose levels were significantly higher in SZ than HCs at baseline (p = 0.005). After 24-week 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’s < 0.01). Six microbes showed significant changes in abundance after 24 weeks of risperidone treatment in SZ (p’s < 0.05), and four of them were associated with the changes in metabolic parameters (p’s < 0.05). At baseline, the abundance of the microbes Christensenellaceae and Enterobacteriaceae were significantly associated with changes in the levels of triglyceride, BMI and HOMA-IR after 24-week risperidone treatment (p’s < 0.05). Conclusions: Changes in gut microbial composition may be a key pathway underlying the metabolic disturbances observed in risperidone treated SZ patients. The present study suggests that microbiota may play a role in antipsychotic treatment associated metabolic side effects in patients with SZ, which can form the basis for the development of novel SZ treatment. Funding: Funding for this study was provided by the National Natural Science Foundation of China (No. 81971253 to X-QS; No. 81401110 to XL), Zhong yuan Innovation Leading Talents of the Thousand Talents Plan (204200510019 to X-QS). Medical science and technology foundation of health and family planning commission of Henan province (SBGJ201808 to X-QS), School and Hospital Co-incubation Funds of Zhengzhou University (No. 2017-BSTDJJ-04 to X-QS), and UiO: Lifesciences Convergence environment, University of Oslo, Norway (project 4MENT to YW, OAA), and Research Council of Norway (#223273 to OAA; #302854 to YW). Declaration of Interest: OAA is a consultant to HealthLytix, and has received speaker’s honorarium from Lundbreck and Sunovion. The other authors declare no conflicts of interest. Ethical Approval: This study was approved by the Human Ethics Committee of the First Affiliated Hospital of Zhengzhou University, China (Approval No. 2016-LW-17). All subjects signed a written informed consent.