Next Generation Probiotics: The Development of Microbial-based Oral Formulations for Microbiome-altering Applications

There are trillions of bacteria living within our bowels. This is normal as they are important in digestion and defence from incoming 'bad' bacteria within our diets. Interestingly, in a range of diseases (examples include Inflammatory Bowel Disease (IBD), cardiovascular disease and obesity) the types of bacterial communities that live in the bowel change. We don't know if these changes in bacterial communities result from poor health, or cause it. However, we do know that patients benefit if we re-introduce bacteria associated with wellbeing. Many clinical trials are currently happening globally to better understand these outcomes.

Recent findings have shown that specific strains of bacteria are needed in the bowel to remedy disease. Unfortunately, these strains of bacteria tend to be sensitive, so we cannot simply include them in regular medicines or pills that patients can take every day. This is because, for example, some don't like to be exposed to oxygen, some can't tolerate changes in acidity, some only thrive in a wet environment and some can't have any pressure/heat exerted on them (commonly applied when compressing a tablet). Consequently the only currently effective way to reintroduce bacteria to the bowel is a procedure known as Faecal Microbial Transplantation (FMT). We take stool from a healthy person (that contains the bacteria we need) and transplant it into the colon of the patient. However, in order for the material to reach the colon without any destruction to the bacteria, we must use either a colonoscope or a naso-gastric tube. Both procedures are invasive, uncomfortable and costly. So this project is designed to find out how to transplant the bacteria using simple oral-administered medicines that patients could take at home.

Currently, we are able to put durable bacteria (such as those found in foods like yoghurts) in medicines that can be taken orally, but we need to be careful with the more sensitive strains of bacteria. As such, we need to create a catalogue of new formulations that suit these bacteria. This catalogue will consist of formulations that are good at keeping oxygen out, formulations that respond to different changes in acidity, and formulations that ensure the bacteria are released only when they reach the colon. In essence, each different formulation will offer a different set of environmental conditions. The catalogue will enable us to identify which formulation offers the best conditions for each different strain of bacteria, to enable the bacteria to be safely transplanted to the colon. We will then need to test whether the bacteria can grow and colonise the bowel, and alter the existing bacterial communities there, as we observe in FMT studies. In order to do this, we will use an artificial human gut, that will expose the formulations to all the different environments that could normally occur in a human. The sophisticated aspect of this artificial model will enable us to mimic the strains of bacteria present within the bowels of patients with a particular disease, and then see if new formulations alter the existing bacterial communities there, to treat the disease.

The ability for us to transplant sensitive strains of bacteria to the colon will be of paramount importance in the near future, and we hope that our catalogue of formulations will be useful not only to understand the bacterial strains to be tested within the scope of this project but also to understand bacteria relevant to different diseases.