The changes of motherhood extend far beyond the visible ones in a woman’s body during pregnancy and breastfeeding. While a lot attention has been given to how the breasts, hormones, and immune system adapt to grow and protect both mom and baby, new research has uncovered a previously overlooked transformation: the restructuring of the mother’s intestine.
An international team of scientists led by Josef Penninger and Masahiro Onji from the Medical University of Vienna has revealed that during pregnancy and lactation, the intestine undergoes a significant transformation. Published in Nature, their study demonstrates that the intestinal surface area nearly doubles, accompanied by a significant architectural reorganization. These changes enhance nutrient absorption, an important adaptation for meeting the increased demands of pregnancy and breastfeeding.
The Intestinal Makeover During Motherhood
Pregnancy is a time of increased nutrient requirements. For decades, scientists have recognized that the mother’s body must meet its own needs while supporting the growing fetus and, later, feeding a newborn. However, this study is the first to provide a molecular and structural explanation for how the intestine adapts to these demands.
Key to this process is the RANK/RANKL signaling system, a molecular pathway influenced by sex and pregnancy hormones. These hormones act on intestinal stem cells, triggering a survival signal that prompts a near-doubling of the intestinal surface area. The changes extend to the structural reorganization of intestinal villi—the tiny, finger-like projections that line the intestine and absorb nutrients. The new configuration likely slows the flow of food through the intestine, maximizing nutrient uptake.
Josef Penninger, the study’s senior author, explained the broader significance:
“Our team has discovered an amazing new way how mothers’ bodies change to keep babies healthy. Hardly anybody knew about this, apart from a few old studies that have largely been forgotten.”
Implications for Evolution and Human Health
These findings are not just a testament to the body’s adaptability; they have significant implications for understanding evolution and human health. The ability of the intestine to transform during reproduction reflects an essential survival mechanism that likely developed across all mammals.
Penninger and his colleagues also explored the impact of impairing this system. In genetically modified mice lacking the RANK/RANKL system in their intestines, the typical villous expansion was significantly reduced. This impairment led to altered breast milk composition, lower weights in nursing pups, and long-term metabolic consequences for the offspring.
These findings highlight the interconnectedness of maternal health and the transgenerational well-being of offspring. By understanding these mechanisms, scientists hope to gain new insights into areas like intestinal regeneration and cancer research.
From Mice to Mothers: Collaborative Research Across Continents
This research was a global effort, with contributions from institutions such as the Institute of Molecular Biotechnology in Vienna, the Life Sciences Institute in Vancouver, the Helmholtz Centre for Infection Research in Germany, and the University of Tokyo, among others. The team used a combination of genetically modified mice and human-derived intestinal organoids—three-dimensional tissue models grown from intestinal stem cells—to uncover how the RANK/RANKL system regulates intestinal changes during reproduction.
The RANK/RANKL system, long recognized as a key player in bone turnover, mammary gland biology, and immune tolerance during pregnancy, has once again proven its evolutionary importance. This system has already been targeted in drugs for bone loss and is under investigation for its role in cancer prevention and immunotherapy.
What makes this intestinal transformation particularly fascinating is its reversibility. Once nursing ceases, the intestine returns to its pre-pregnancy state. Understanding how this process works could open doors to therapies for conditions like intestinal cancer or regenerative disorders.
The Bigger Picture
This study sheds light on a critical yet underexplored aspect of motherhood. The intestine’s transformation is not just an adaptation; it is a life-support system that ensures the health of both mother and child. By doubling its surface area and optimizing nutrient absorption, the intestine helps mothers meet the immense demands of pregnancy and breastfeeding, while also shaping the future health of their offspring.
As lead author Masahiro Onji emphasized:
“Our study shows that the impairment of this intestinal expansion during pregnancy changes the milk of nursing mothers, with long-term consequences for the babies’ health. This underscores how deeply interconnected maternal and offspring health truly are.”
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