People living with long-term inflammation of the bowel, such as Crohn’s disease or ulcerative colitis, face a higher risk of developing bowel cancer. Researchers at AITHM are investigating the influence of age on gut health and whether specialised immune cells in the gut can help protect against cancer. Understanding these relationships could ultimately lead to treatments that delay, or even prevent, bowel cancer.
Bowel cancer (also known as colorectal cancer) was the fourth most commonly diagnosed cancer in Australia in 2024. While most cases occur in people over 50, rates among people in their 30s and 40s are steadily rising.
AITHM’s immunology group leader Dr Roland Ruscher and PhD candidate Sarah Gillert are exploring how the early life environment of the gut shapes protective immunity against bowel cancer in adults. “Our research focuses on beneficial immune cells in the gut, how they are established in early life and how they respond to changes in the intestinal microbiome,” Dr Ruscher said.
Everyone’s gut microbiome, which is a collection of microbes such as bacteria, viruses and fungi that live in and on many parts of the body, is unique. “A diverse and abundant community of beneficial microbes may help reduce the risk of developing colorectal cancer,” Ms Gillert explained. “In contrast, a dysbiosis — when important beneficial microorganisms are reduced and replaced by harmful microbes — can have lasting negative consequences.”
There are many factors that can contribute to a dysbiosis in the gut. “Nutrition, alcohol intake, medication such as antibiotics, ageing and a lack of exercise can all play a role,” Ms Gillert said. “There is research suggesting that people who receive antibiotics early in life may be more likely to develop bowel cancer years later, likely due to long-term effects of an altered microbiome.”
Ms Gillert’s research focuses on intraepithelial lymphocytes (IELs) –– specialised immune cells that subdivide into multiple subsets and reside within the epithelial gut lining and act as a rapid front-line defence. “Although IELs have been known for decades, the roles of specific IEL subsets in colorectal cancer remain understudied,” she said.
Using advanced preclinical experimental systems, Ms Gillert is examining how IEL subsets interact with colorectal cancer cells and whether they can limit tumour growth. Early findings by Ms Gillert show that IELs can directly reduce cancer cell survival in cell culture conditions, offering new clues about how these cells may protect the gut.
“We are also using so-called ‘fate mapping’ approaches to track IELs over time, revealing how they move into or around colorectal cancer tumours, and whether IELs formed in early life behave differently from those generated in adulthood,” Ms Gillert said.
The next stage of Ms Gillert’s and Dr Ruscher’s research will examine whether IELs derived from microbiologically diverse early-life environments are more effective at controlling tumour growth than IELs from microbially more restricted conditions.
Ultimately, the team aims to understand whether early-life immune development influences bowel cancer risk decades later. “By understanding how the protective IEL cells develop and function, we hope to identify ways to strengthen gut immunity and potentially even prevent bowel cancer in people in Australia and worldwide,” Dr Ruscher said.