Start date: 2025
Award: £111,102
Status: Active (2025-2027)
What issue does this study address?
Multiple intestinal diseases, including bacterial infections, inflammatory bowel disease/Crohn’s Disease, and in cancer patients receiving chemotherapy, exhibit increases in the number of our cells that die that goes along with changes to the intestinal bacteria populations. Despite being widely reported across these clinical settings, the nature of the relationship between cell death and our intestinal bacteria has been a long-standing mystery; essentially the scientific equivalent of the chicken and the egg, do changes in these bacterial populations drive disease or does the disease itself drive changes to intestinal bacteria?
The cells that line our gut shed and die in a similar way to our skin, and the bacteria in our gut can use these dead cells as a food source. Certain inflammatory conditions such as Crohn’s disease can ulcerative colitis, or treatments like chemotherapy used in bowel cancer, can increase the rate of cell death in our gut lining. This is seen alongside increases in different types of gut bacteria. The relationship between the two has been a long-standing mystery; essentially the scientific equivalent of the chicken and the egg. Do changes in these bacterial populations drive disease or does the disease itself drive changes to intestinal bacteria?
This research team has recently revealed that the bacteria are driving disease, and want to further understand how these processes affect our immune system and gut health.
What are the aims and how could this work help people with bowel disease?
The research team will examine how chemotherapy and certain bacteria affect the immune system in the guts of mice, and how all these factors contribute to gut inflammation and injury. Information about these processes could potentially lead to new treatments for inflammatory bowel disease, and other bowel conditions.
The research team
This project will be led by Dr CJ Anderson, a Wellcome Trust Career Development Fellow at the University of Edinburgh.
Report for the public (Summary of interim report)
Intestinal damage and subsequent repair is a complicated multi-factorial problem. When damaged, for example via excess inflammation, bacterial infection, or drugs such as chemotherapy, our intestinal tract must sense this damage and engage with the reparative process. At the same time, this damage process causes the death of the cells that line our intestinal tract. This cell death directly leads to changes in the intestinal bacteria through a process termed death-induced nutrient release (DINNR), which delays tissue repair. It is unclear how our bodies simultaneously deal with this intestinal damage and the changing bacterial community.
Our work seeks to answer: how do intestinal damage signals recruit and activate immune cells? How do changes to intestinal bacteria interfere with the ability to recruit these immune cells? How do specific immune cell types influence intestinal damage and subsequent repair?
Thus far, we have defined the changes in immune cells during chemotherapy-induced intestinal damage and subsequent repair and have shown that the initial changes to the intestinal bacterial community do not influence initial immune cell recruitment. Further, we have optimised the systems and tools necessary to get rid of specific immune cells during initial injury and subsequent transition to repair.