A striking illustration of gut plasticity emerges from animals enduring prolonged fasting periods, such as hibernating creatures or phyton snakes abstaining from food for months. During these phases, the gut undergoes a remarkable reduction of up to 50 percent in size, which, upon resumption of feeding, swiftly regains its original dimensions within a few days.
The Colombani Andersen laboratory, situated within the section of Cell & Neurobiology at the Department of Biology, University of Copenhagen, focuses on unraveling the mechanisms governing gut plasticity using the fruit fly, Drosophila, as a model organism. Their findings have recently been published in the scientific journal Nature Communications.
Crucially, the ability of the gut to resize itself is predominantly conserved. Consequently, in human pregnancy, the gut expands to accommodate increased nutritional demands, facilitating optimal nourishment for fetal development.
Dr. Ditte S. Andersen elaborates on their research, stating, “Leveraging the extensive genetic toolkit offered by the fruit fly, we explored the mechanisms dictating nutrient-dependent gut resizing.”
Their findings reveal that nutrient scarcity leads to an accumulation of progenitor cells that remain undifferentiated, resulting in gut shrinkage. Upon reintroduction of food, these dormant progenitor cells swiftly differentiate into mature cells, initiating gut regrowth.
Dr. Ditte S. Andersen further explains, “We have pinpointed activins as pivotal regulators in this process. Under nutrient-restricted conditions, activin signaling is significantly suppressed, but upon refeeding, it becomes reactivated and crucial for progenitor cell maturation and subsequent gut resizing. The activin-dependent modulation of gut size holds physiological significance, as inhibiting activin signaling diminishes the survival rate of flies subjected to intermittent fasting.”
While regulators of organ plasticity are imperative for host adaptation to dynamic environments, these same signals often undergo dysregulation in cancer. Notably, mutations impacting activin signaling are prevalent in cancer cells across various tissues. Hence, their study serves as a foundation for exploring the association between aberrant activin signaling and the onset of colorectal cancers, offering insights into potential therapeutic avenues involving anti-activin strategies for treating such malignancies.
