Identifying the influence of the microbiome and metabolome on the normal and malignant murine intestinal stem cell

Julian Marchesi’s research revealed that a diet high in fibre (in particular black raspberries) can reduce the number of cancer stem cells in an early bowel cancer tumour

  • Topic: Colorectal cancer
  • Institution: Cardiff University
  • Country: United Kingdom
  • Status: Completed
Researcher: Julian Marchesi


On average, more than 40,000 people a year are diagnosed with bowel cancer in the UK. Lifestyle and diet changes could have prevented up to half of these cases. Unsurprisingly bowel cancer is strongly linked to diet, for example a high fibre, fruit and vegetable diet is associated with a lower cancer risk. However, understanding the reasons for these links is complicated, as diet can affect a person’s immune system and the bacteria that live in the bowel.

Ultimately, to gain a better understanding, we need to study the stem cells that are responsible for maintaining a healthy bowel, as it is damage to these cells that leads to cancer. To study this, we have used mouse models in which we can remove the Apc gene; this alteration is the most commonly found change in bowel cancer cells. We have used these models to examine what effect different dietary components have on normal and cancer stem cells.

Aims and objectives

Our aim was to understand how food and the bacteria that live in the intestine can affect the behaviour of a normal and a cancerous intestinal stem cell. A greater understanding of this behaviour will help us understand if there is a specific reason why certain food is associated with protection or promotion of bowel cancer. This knowledge would help us exploit food for its maximum cancer prevention benefits.

How the study was done

We performed this work using state of the art mouse models of bowel cancer in which the normal and cancer stem cells have been labelled. This label allowed us to identify and isolate them to grow “mini-guts” in the laboratory. We treated these mini-guts with different food and bacterial products to identify what effect they had on the ability of the stem cells to grow and create new mini-guts.


Using our models, we have made key findings in the way that fruit and fibre prevent bowel cancer. Specifically, we investigated black raspberries and a compound called butyrate, which is made by bacteria from the fibre in diet. We discovered that, at the very earliest stages of bowel cancer, when it is made of only a few cells, a diet high in these items can reduce the number of cancer stem cells in the tumour.

Unexpectedly, we also learned that when levels of butyrate drop, for example during periods when you eat less fibre, the number of stem cells in an early tumour rapidly grows. This work emphasises the importance of maintaining a healthy diet to help prevent damaged stem cells developing into bowel cancer.