Professor Chris Probert, a Professor of Gastroenterology in the Institute of Systems, Molecular and Integrative Biology at the University of Liverpool, is leading a team seeking to understand the connection between the human metabolome and inflammatory bowel disease (IBD).
Inflammatory bowel disease (IBD) is a term used to describe two different conditions: ulcerative colitis and Crohn’s disease. Around every 1 in 123 people in the UK suffer from either disease, and both ulcerative colitis and Crohn’s disease can be life-changing, often leading to surgery and increased risk of bowel cancer. Professor Chris Probert and his team are investigating how the human metabolome impacts these diseases.
The metabolome is the suite of small molecule organic compounds that regulate biological processes that are found within a biological sample. The sample itself could be anything from a cell, to a sample of tissue, an organ or an entire organism. Metabolomics is the study of these small molecules, which have different roles within their environment, such as binding to larger molecules to alter a function, or providing a cell signalling role. Many pharmacology drugs are also considered to be small molecules.
The metabolome aids the growth and healthy function of human cells and the bacteria we naturally carry as part of our microbiome (the microbes that coexist in our bodies, most notably within our intestinal tract). Professor Probert and his team are investigating whether inflammation of the gut in IBD is aligned with the bacteria in the gut and whether there is a relationship to the chemicals found in the metabolome. “I often think of it in terms of a forest metaphor”, described Professor Probert. “Think of a forest with a good mix of different healthy types of tree. That’s what a healthy gut, a microbiome, might look like. Overall, people with IBD have a less diverse mix of trees. People with Crohn’s disease have a mixed forest but with fewer types of tree. There is no one type of forest that fits all patients, everyone is different so the bacteria in their microbiome is different.”
Professor Probert and his team are studying stool samples of around 250 children, half with newly diagnosed IBD and half without, to identify whether their level of inflammation correlates to the chemicals and bacteria in their microbiome. Working in partnership with Liverpool’s Alder Hey Children’s Hospital to collect samples, and with additional research input from researchers at Birmingham Children’s Hospital and Bristol Royal Hospital for Sick Children, the team hope to identify groups of bacteria responsible for driving inflammation and if changes to the composition of the microbiome can reduce levels of disease.
Professor Probert, said: “Previous research has established a clear link between activity in the microbiome and levels of disease. For instance, the patterns of two or three compounds are different in people with or without IBD. There are also correlations between different types of bacteria (species levels) and associated inflammation. If we change the compounds evident in the gut through antibiotics and other treatment, thereby changing the bacterial community, do levels of inflammation increase or reduce as we’d like?”
The research builds on years of previous studies including three papers studying the impact of iron on the structure of the microbiome. Patients with IBD are commonly found to have iron deficiency and impaired iron absorption due to tissue inflammation. By changing the diet of mice, they found that iron bound to a sugar complex didn’t affect the intestinal microbiome whereas ferrous sulphate, most commonly given as an iron supplement exacerbated intestinal inflammation.
“There is much that we do know about IBD and the microbiome but so much that we don’t” describes Professor Probert. “We are all different and we’re seeing different trees (bacteria) that survive. It’s much less likely that just one group of bacteria is driving the diseases. It’s the same havoc and symptoms experienced by each patient but they’ve got there by different paths and different bacteria.”
Professor Probert, added: “Around the world IBD is prevalent in some countries more than others. Those living in ‘western’ societies are more likely to have IBD with some arguing that a ‘western’ diet and lifestyle causes changes to the bacterial community in the gut which is harmful. We know the increased use of antibiotics and other factors such as smoking cause changes in the gut microbiome destroying diversity. But unfortunately, it’s not that clear cut. If we can better identify the bacterial compounds associated with disease then we might be able to change a person’s microbiome through the introduction of tailor-made compounds that reduce inflammation or disease.”
The current research into IBD in children is funded by GutsUK and the British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) and will report findings in 2023.
Anyone interested in collaborating with the team at the Institute of Systems, Molecular and Integrative Biology or any of the researchers who are part of the Human Microbiome team in the Microbiome Innovation Centre, please see further details here.
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