Using Culturomics to Characterize the Gastrointestinal Microbiota of Donors for Patients with Bipolar Disorder Experiencing Depression
Gut Microbiota , Bacteria , Depression , Mental Health , Culturomics
Depressive disorders such as bipolar disorder (BD) affect more than 310 million people worldwide, reduce quality of life, co-occur with other physical disorders, and increase risks of premature death. This high prevalence reflects the challenges in the tolerability and efficacy of current treatments. Bacteria residing in the human gastrointestinal tract communicate with the central nervous system through a bi-directional network, referred to as the gut-brain axis, which can influence mood and behaviour. Fecal microbiota transplantation (FMT) has been shown to alter the gut bacterial composition of recipients. In a phase 2/3 double-blinded randomized controlled trial (RCT) completed in 2022, participants diagnosed with BD were randomized 1:1 to receive either rigorously screened and processed donor stool (allogenic FMT) or their own stool (autologous FMT) via colonoscopy. Fecal samples were collected from donors and participants at baseline, 3, and 6 months. This thesis will provide a review of the current literature on the role of the gut microbiota, depressive disorders, and methods of altering gut microbiota composition and i) Results of cultured and isolated bacteria from the donor stool with ii) Species and/or strain level identification; and iii) Compare the metagenomic community profiles of the donors to the bacteria isolated from culturing. Using a culturomics approach, donor fecal samples were cultured on 10 different selective and differential media. The taxonomy of bacterial isolates was identified using MALDI-TOF mass spectrometry, 16S rRNA gene sequencing, and Sanger sequencing. Bacterial community profiles from fecal samples were characterized using shotgun metagenomics. From the donor stool, 78 different species of bacteria were isolated across 43 genera including Bacteroides, Bifidobacterium, Collinsella, Streptococcus, Dorea, and Coprococcus. Patients diagnosed with BD, experiencing severe depression who have undergone FMT treatment, have shown reduction in depressive symptoms and different gut bacterial composition. Isolated bacteria from donor stool provides a collection of viable species of interest for future use. These findings add valuable insights into FMT as a method to modify the gut microbiota and analyze the restorative potential to inform the development of further studies examining the relationship between the gut-brain axis and depressive disorders.