Recent research conducted by scientists at the Francis Crick Institute has uncovered significant changes in the small intestine of pregnant mice. These findings suggest that the gut undergoes both reversible and irreversible transformations to support pregnancy and prepare for subsequent pregnancies. The study highlights how reproduction affects metabolism and intestinal growth, providing new insights into mammalian physiology.

Intestinal Remodeling: A Crucial Adaptation for Reproduction

In pregnant mice, the small intestine undergoes remarkable changes, becoming longer as early as seven days into gestation. By the end of pregnancy, it increases in length by approximately 18%. This adaptation persists postpartum, even after lactation concludes, indicating a partially irreversible transformation. Moreover, subsequent pregnancies further enhance this effect, resulting in an even longer intestine compared to the first pregnancy.

During pregnancy, not only does the intestine elongate but also its villi and crypts grow deeper and longer. However, these structures revert to their pre-pregnancy state within seven days after weaning. Intriguingly, during a second pregnancy, villi do not grow more than they did during the first. Researchers believe that these changes are designed to facilitate increased nutrient absorption necessary for maternal health and offspring development. Through experiments involving dietary modifications, including probiotic intake, scientists confirmed that these physiological alterations occur independently of nutritional factors.

Molecular Mechanisms Driving Intestinal Changes

Investigations revealed rapid proliferation of intestinal epithelial cell precursors early in pregnancy, with newly generated cells migrating faster up the villi. This process continues into lactation but reverts to baseline levels shortly after weaning. Genetic analysis demonstrated substantial changes in enterocytes, the nutrient-absorbing cells located in the villi, primarily associated with heightened metabolic activity.

A key finding was the increased expression of SGLT3a, a membrane protein responding to sodium and protons rather than glucose. This protein accounted for roughly 45% of villi growth triggered by reproduction, although it wasn’t essential for overall small intestine lengthening. Supplementing female mice diets with sodium induced villi growth even in non-pregnant individuals, suggesting hormonal influences play a critical role. Pseudo-pregnant mice exhibited similar effects, reinforcing the hypothesis that reproductive hormones activate the gene responsible for SGLT3a production. These discoveries underscore the intricate interplay between genetics, hormones, and metabolism in shaping the gut’s response to pregnancy challenges.