Snake research reveals insights into human intestinal regeneration

All animals have some ability to repair and replace the lining of their intestines, a process called intestinal regeneration. In mammals, including humans, this constant but relatively minor turnover of cells helps the gut keep up with daily food requirements. It is achieved by stem cells that originate in the intestinal crypts: microscopic depressions in the intestinal wall.

In sharp contrast, snakes that feed infrequently, such as boas and pythons that can go weeks without food, do not have intestinal crypts, but undergo some of the most extreme examples of intestinal regeneration found in the animal kingdom. When these snakes fast for long periods, their intestines atrophy, shrink and become almost non-functional.

However, when fed, their intestines undergo massive regenerative growth, more than doubling in mass within 48 hours and rebuilding much of the intestinal cells and structures needed to digest and absorb food. This change is also accompanied by major changes in the physiology and metabolism of snakes.

To understand how these large snakes can regenerate their intestines without intestinal crypts, scientists at the University of Texas at Arlington, UT Southwestern Medical Center and the University of Alabama sequenced the pythons’ RNA genes. By learning more about this process in reptiles, the researchers hope to better inform other scientists working to improve the diagnosis and treatment of gastrointestinal diseases in humans, such as diabetes, Crohn’s disease, celiac disease and cancer .

“We used single-cell RNA sequencing to study intestinal regeneration in pythons and found that they use conserved pathways that are also found in humans, but activate them in unique ways,” said Todd Castoe, professor of biology at UT Arlington and author of the study published in Proceedings of the National Academy of Sciences.

“Interestingly, we found that the signaling pathways that regulate python regeneration share key similarities with those observed in humans after undergoing Roux-en-Y gastric bypass to facilitate weight loss and treatment of type 2 diabetes 2,” said study co-author Siddharth Gopalan. paper and a Ph.D. student in the laboratory of Dr. caste

These findings provide new insight into the fundamental links between gut regeneration and how the body adjusts its metabolism in response to changes such as nutrient availability and exposure to stress. The research also helps explain how pathways involved in python regeneration may function similarly in other vertebrates, including humans, and therefore represent potential targets for therapeutic intervention to treat intestinal or metabolic diseases.

“Our findings also shed light on the importance of a specific intestinal cell type, called BEST4+ cells, in coordinating the regeneration process,” said Castoe. “These cells are present in pythons and humans, but absent in commonly studied mammals such as mice, but act as central regulators of the early phases of regeneration by favoring lipid transport and metabolism. These findings highlight the important and largely neglected roles that BEST4+ cells likely play in human intestinal function.”

Together, these findings expand our understanding of gut physiology.

“Learning more about digestion in other animals gives us a broader understanding of the evolutionary design of these important body functions,” Castoe said. “This new information will inform our understanding of the body with the goal of improving the treatment and prevention of many common human digestive disorders.”