Novel Biomanufacturing Strategies for Scalable Production of Non-Donor-Derived FMT Products

**The Bacterial Microbiome: Key to our Health** Bacteria from a critical element of who we are: indeed, we carry approximately the same amount of bacterial cells around with us as the human cells which make up our body. These bacteria that grow and thrive on all of our internal and external surfaces are known as our microbiome. We play host to several different microbiome communities, including our Skin, Gut, Vaginal and Oral microbiomes. We have recently begun to understand that these bacterial communities impact/influence our health and wellbeing. This is not limited to infections: we now understand that an imbalanced, or dysbiotic, microbiome can cause or contribute to a very broad range of different health conditions, including Crohn's disease, Ulcerative Colitis, various cancers, obesity, and inflammatory diseases. **Modifying the Microbiome: Challenges** Having now understood the impact of our bacterial composition, we are now attempting to manipulate dysbiotic microbiomes, with a view to improving health outcomes. One method of microbiome manipulation is to fully remove a dysbiotic microbiome through administration of antibiotics, and replace it with a healthy microbiome community, which has been derived from a healthy donor. This concept is broadly similar to organ transplantation. Microbiome transplants have been particularly successful for treatment of diseases directly linked to dysbiotic gut microbiomes (e.g. Ulcerative Colitis, Crohn's disease), and is called Faecal Microbiota Transplant, or FMT. However, despite initial successes, it is currently challenging to use FMT in a mass-market fashion, or for the treatment of more than a handful of diseases. This is largely due to the challenges involved in finding appropriate microbiome donors, and in collecting samples in an economical, safe and reproducible way. **Project Goals** Addressing these issues forms the basis of this project application. Our consortium, a collaboration between UK-based (CC Bio) and Japanese-based (Metagen Therapeutics/Keio University) entities, aims to develop methods for the production of standardised, reproducible bacterial communities in the laboratory which replicate those derived from the faeces of healthy donors. By successfully developing this process, and decoupling the benefits of FMT from the challenges of donor identification/collection, we will enable the drug development community to produce FMT products on a mass market scale. This project outcome will greatly expand the utility of FMT, returning revenue to the project team via licencing of these processes to Pharma customers, or through production of FMT products on their behalf, as a Contract Development and Manufacturing Organisation, or CDMO.