To discover how these large snakes can regenerate their intestines without the presence of intestinal crypts, scientists sequenced the RNA genes of pythons. By gaining insight into this regeneration process in reptiles, the aim is to assist other researchers who are working towards enhancing the diagnosis and treatment of gastrointestinal conditions in humans, which include diabetes, Crohn’s disease, celiac disease, and cancer.
All animals have some ability to repair and replace the tissue lining their intestines, a process known as intestinal regeneration. For mammals, including humans, this ongoing but relatively minor cell turnover enables the intestine to meet the daily dietary demands. This is achieved through stem cells that originate from intestinal crypts—tiny indentations in the intestinal wall.
In stark contrast, snakes that eat less frequently, such as boas and pythons, which can survive for extended periods without food, do not have intestinal crypts. Yet, they exhibit some of the most remarkable instances of intestinal regeneration in the animal world. During prolonged fasting, their intestines become shrunken and nearly non-functional. However, upon eating, their intestines rapidly regenerate, more than doubling in size within 48 hours and reconstructing much of the cellular structure necessary for digestion and nutrient absorption. This transformation also leads to substantial changes in the snakes’ physiology and metabolism.
To better understand how these large snakes can regenerate their intestines in the absence of intestinal crypts, researchers from The University of Texas at Arlington, UT Southwestern Medical Center, and the University of Alabama sequenced the RNA genes of pythons. Insights gained from this research in reptiles aim to aid scientists focused on advancing the diagnosis and treatment of gastrointestinal diseases in humans, including issues like diabetes, Crohn’s disease, celiac disease, and cancer.
“We utilized single-cell RNA sequencing to investigate intestinal regeneration in pythons and discovered that they engage conserved pathways also found in humans, but activate them in distinctive manners,” stated Todd Castoe, a biology professor at UT Arlington and the article’s lead author published in the Proceedings of the National Academy of Science.
“Interestingly, we identified that the signaling pathways regulating python regeneration have notable similarities to those observed in humans following Roux-en-Y gastric bypass for weight loss and type 2 diabetes management,” remarked Siddharth Gopalan, a co-author and Ph.D. student under Dr. Castoe’s supervision.
These discoveries provide fresh perspectives on the essential connections between intestinal regeneration and how the body adjusts its metabolism in response to factors like nutrient availability and stress exposure. This research also elucidates how the pathways involved in python regeneration might function similarly in other vertebrates, including humans, highlighting potential targets for therapeutic strategies aimed at treating intestinal or metabolic disorders.
“Our research also emphasizes the significance of a particular intestinal cell type known as BEST4+ cells, which coordinate the regeneration process,” Castoe explained. “These cells are found in both pythons and humans but are missing in commonly studied mammals like mice. They play a crucial role in the early phases of regeneration by facilitating lipid transport and metabolism. This underscores the vital, yet often overlooked, functions that BEST4+ cells likely serve in human gut activity.”
Collectively, these findings enhance our comprehension of intestinal biology.
“By gaining more insight into digestion across different animals, we develop a more comprehensive understanding of the evolutionary blueprint of these vital bodily functions,” noted Castoe. “This new knowledge aims to enhance our comprehension of the human body, ultimately improving the treatment and prevention of various digestive issues.”
This project received support from the National Science Foundation award IOS-655735.
