Differences in intestinal microflora and metabolites between patients with schizophrenia, depression, bipolar disorder, and healthy subjects: protocol for a case-control study

Background and objectives: The human intestine contains a large amount of commensal bacteria. Under normal conditions, the intestinal microflora is stable, forms intestinal biological barriers, and promotes the growth and development of the organism. However, changes in the external environment can lead to disturbances in intestinal micro-organisms, causing host dysfunction and resulting in various types of disease. This study will investigate the role of intestinal microbes in the development of depression, bipolar disorder, and schizophrenia. Design: A case-control study. Methods: We recruited 50 patients with schizophrenia, 50 with depression, 50 with bipolar disorder, 50 with bipolar depressive episode, 50 with manic or hypomanic bipolar episode, and 50 age- and sex-matched healthy individuals who received physical examinations at the Department of Psychiatry of Xijing Hospital (China). Outcome measures: The primary outcome measure is the degree of change in fecal bacterial microflora after 3 months of pharmaceutical treatment. The secondary outcome measures are the type and content of small molecule metabolites in feces, the Hamilton Depression Scale score, the Young Mania Rating Scale score, the positive and negative syndrome scale score, and the Global Assessment of Functioning scale score before vs. after treatment. Discussion: The results of this study will reveal changes in intestinal microflora and metabolic patterns in patients with schizophrenia, depression, and bipolar disorder. These data may lead to biomarkers for disease diagnosis and provide new directions for investigation of possible mechanisms underlying the development of mental disorders. Ethics and dissemination: This study was approved by Medical Ethics Committee, Xijing Hospital, China (approval No. KY20172048-1). This study was disigned in May 2017, received ethical approval on September 6, 2017, and registered on October 18, 2017. Patient recuritement initiated in November 2017 and ended in February 2018. Genomics and metabolomics detection and data analysis initiated in March 2018 and will end in December 2018. Results will be disseminated through presentations at scientific meetings and/or by publication in a peer-reviewed journal. Trial data will be publicly accessible via ResMan. Trial registration: This trial was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR-ROC-17013029). Protocol version: 2.0.