Your gut encompasses everything from your stomach, small intestine, and your large intestine, commonly known as the colon. The gut can be very complex, as each stage has different functions and conditions. The stomach is highly acidic in order to break down food, whereas the colon has an environment that is low in oxygen and is involved in removing waste from our body.

The colon is home to our gut microbiota. The gut microbiota is home made up of to trillions of microorganisms that play a vital role in keeping us healthy.

Our Colon Model Facility here at the Quadram Institute allows us to mimic the complex conditions of the colon to learn more about the important role of our gut microbiota.

We can use models that represent our digestive system as a whole as it can be useful to see if the compound, we are testing can make it through some of the tougher conditions of the stomach and small intestine. An example of a model that represents the whole digestive system we have at the Quadram Institute is the Simulator of the Human Intestinal Microbial Ecosystem (SHIME®).

The challenge of studying the gut microbiota

Studying the gut microbiota inside the human body is difficult. Firstly, every person’s microbiota structure is unique, and it changes depending on what we eat, how we live, and even where we live.

Secondly, while human and clinical studies are incredibly valuable, they can be complex, expensive, and take a long time.

That’s where colon models come in. Colon models allow us to simulate the human colon conditions outside the human body, by incubating colon medium, maintaining a temperature of 37°C, creating anaerobic conditions, and regulating pH.

How colon models can help us study how food and other compounds affect our health

Once the colon conditions are stabilised, the model can be inoculated with a human stool sample to introduce the gut microbiota. At that time, various treatments such as food, nutrients, drugs, prebiotics or probiotics can be added to study their effects on the microbial community in our gut and how these changes may be reflected in overall human health.

Our Colon Model Facility at the Quadram Institute provides scientists with cutting-edge gut models to carry out highly impact research on the human gut microbiota.

The models can help us explore how diet shapes the gut microbiome microbiota and how certain foods reduce disease risk by supporting beneficial gut microbes. Dr Paul Kroon’s group , for example, studied the ability of pomegranate to inhibit the production of proatherogenic trimethylamine (TMA) by the human gut microbiota. As pomegranate showed a promising prebiotic effect for the inhibition of TMA, this work was taken further to a human intervention study called the TESSA study.

A key area of research we are working on is understanding what role gut microbes play in breaking down plant compounds, such as polyphenols into health-promoting metabolites.

In addition, other research carried out here at the Colon Model Facility to evaluate the prebiotic effects of foods on the changes of the human gut microbiota structures. For example, almond treatment altered the composition of gut microbiota by stimulating the growth of bifidobacteria and Eubacterium rectale whereas bergamot extract enhanced the growth of bifidobacteria and lactobacilli species and reduced the population of clostridia.

Studying how gut microbes change over time

A key capability of using colon models is that they allow us to see how gut microbiota adapt to dietary changes over time, including over days, weeks and even months.

Professor Arjan Narbad’s group here at the Quadram Institute used the Colon Model Facility to show that reducing iron availability in the gut leads to a decrease in disease-causing bacteria in the gut over 24 hours. Similarly, previous work in the Narbad group showed that treatment with garlic powder altered the structure of the gut microbial community over 24 hours.

While our models are often used to look at the impact of diet on our gut microbiota, it is not limited to research within the scope of food and nutrition. The colon models can be used for a variety of research topics, including pathogenic diseases and their treatment. For example, there is ongoing research which is looking to develop treatment for reoccurring Clostridium difficile infections, using donors who have a healthy gut microbiota. These models allow us to ensure that the treatment provides longer term benefits to the patient and stops the cycle of reoccurring infections, by changing the recipients gut microbiota composition.

Exploring variation in gut microbiota between people

By working with colon models, researchers can run controlled experiments without the confounding effects of the host. Studying the human gut microbiome directly in people is a bit challenging as people are subject to many daily variations such as changes in sleep patterns, mood, hormonal cycles, and health status, which make it difficult to isolate the impact of a single intervention or treatment.

In contrast, colon models remove theses variables allowing researchers focus on one factor at a time. For example, colon models can be used to compare how different diets influence the gut microbiome, or test how gut microbiota transform specific compounds into forms that are more beneficial for the body. For example, a group of researchers here at the Quadram Institute across the groups of Dr Paul Kroon and Professor Arjan Narbard, led by Priscilla Day Walsh used to the colon model to show the production of proatherogenic trimethylamine (TMA) by the human gut microbiota varies between individuals.

Similarly, Emad used the colon model to investigate how the metabolism of the dietary colourants called anthocyanins by the gut microbiota differs across individuals.

Towards better heath

We are currently collaborating with clinicians at the Norfolk and Norwich University Hospital to recruit patients and collect stool samples from individuals with conditions such as Parkinson’s disease, Crohn’s disease, and diabetes. This partnership will help us better understand how the gut microbiota differs in these patients, and how we might help restore a healthy gut through the use of prebiotics, probiotics, and faecal microbiota transplantation (FMT).

The insights we gain from our colon models are helping to answer big questions about the impact of gut microbiota on our health. Ultimately, this research could inform better nutrition advice, innovative therapies, and new strategies to support human health.