Small intestine adjusts size according to nutritional intake: Study

The remarkable adaptability of the gut, known as gut plasticity, is exemplified in animals enduring prolonged fasting periods, such as hibernating species and phyton snakes, which can go for months without eating. During these periods, the gut can shrink by up to 50 per cent, only to recover its size within a few days of refeeding.

Researchers at the Colombani Andersen lab, situated within the section of Cell & Neurobiology at the University of Copenhagen's Department of Biology, have employed the fruit fly, Drosophila, as a model organism to investigate the mechanisms governing gut plasticity. Their findings, recently published in the scientific journal Nature Communications, shed light on this fascinating biological phenomenon.

Crucially, the fruit fly's gut displays a similar ability to resize in response to changes in nutrient availability. This adaptability is reminiscent of the gut's behaviour during pregnancy in humans, where gut size expands to accommodate increased nutritional demands necessary for fetal development.

Dr Ditte S. Andersen, leading the research, highlights the significance of leveraging the fruit fly's genetic tools to delve into the intricacies of nutrient-dependent gut resizing. Their investigations revealed that



under conditions of nutrient deprivation, progenitor cells accumulate in the gut but fail to differentiate into mature cells, resulting in gut shrinkage. However, upon refeeding, these stalled progenitor cells swiftly differentiate into mature cells, facilitating gut regrowth.

Ditte S. Andersen continues, "We have identified activins as critical regulators of this process. In nutrient-restrictive conditions, activin signalling is strongly repressed, while it is reactivated and required for progenitor maturation and gut resizing in response to refeeding. Activin-dependent resizing of the gut is physiologically important as inhibition of activin signalling reduces survival of flies to intermittent fasting".

The study underscores the essential role of organ plasticity regulators in enabling organisms to adapt to dynamic environmental changes. However, disruptions in these signalling pathways are often implicated in cancer development. Mutations affecting activin signalling are frequently observed in various cancer cells, including colorectal cancers. Thus, the research provides valuable insights into the potential link between aberrant activin signalling and colorectal cancer development, paving the way for exploring anti-activin therapeutic strategies in cancer treatment.