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Pregnancy and Breastfeeding Cause Major Changes in Mothers’ Intestines

by Ella

A groundbreaking study led by Josef Penninger and Masahiro Onji from the Medical University of Vienna has revealed that pregnancy and breastfeeding cause significant, structural changes in the intestines of mothers. This research, published in Nature, highlights how the intestines undergo a complete reorganization during these phases, doubling in surface area to meet the heightened nutritional demands of both the mother and her growing child.

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Pregnancy and lactation trigger a range of changes in the body, and for decades, the mechanisms behind these adaptations have remained largely unclear. This new study provides the first genetic and mechanistic evidence of how the intestinal epithelial cells expand during reproduction, offering important insights that could affect transgenerational health outcomes for children.

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The research team, working with genetically modified mice and intestinal organoids from both mice and humans, discovered that the intestinal villi—finger-like projections in the small intestine that help absorb nutrients—grow significantly during pregnancy and breastfeeding. The doubling of the villous surface area was found to be regulated by the RANK receptor/RANK ligand (RANK/RANKL) system, which is influenced by sex hormones and lactation hormones. When the RANK/RANKL system was disabled in mice, the expansion of the villi was significantly impaired during pregnancy and breastfeeding.

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This discovery has broad evolutionary and medical implications. The RANK/RANKL system has long been recognized for its role in bone turnover, mammary gland biology, and immune tolerance during pregnancy. Penninger’s team has previously contributed to developing drugs that address bone loss and are exploring clinical trials for breast cancer prevention. Now, their research demonstrates that this system plays a critical role in enabling the intestinal changes needed to nourish offspring during pregnancy and lactation.

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The study’s lead author, Masahiro Onji, explains that the absence of the RANK/RANKL system results in altered milk production, which, in turn, leads to reduced baby weight and long-term metabolic consequences for the offspring. This underlines the importance of the intestinal expansion process during pregnancy and breastfeeding for the health and development of the baby.

The adaptation of the mother’s intestines during these critical periods is vital to support the nutritional demands of both mother and baby. Penninger notes that this study is the first to provide a molecular and structural explanation for how the intestine changes to meet the increased nutritional requirements during pregnancy and breastfeeding—a process likely seen across all mammalian species.

The study also uncovered how these changes are controlled by female sex hormones, which act on stem cells in the gut via the RANK/RANKL system. This interaction signals the intestinal cells to grow larger, leading to a nearly doubled intestinal surface area. The expanded surface area enhances the absorption of essential nutrients such as sugars, proteins, and fats. Additionally, the intestinal villi undergo an architectural transformation, which likely slows down the movement of food, maximizing nutrient uptake.

Penninger emphasizes the significance of this discovery, stating that the team has uncovered a novel and amazing mechanism by which mothers’ bodies adjust to ensure the health of their babies. The implications of these findings may extend beyond maternal health and lead to new insights into intestinal cancer, gut regeneration, and even tumor growth, potentially offering new therapeutic strategies.

The collaborative research involved several prestigious institutions, including the Medical University of Vienna, the Institute of Molecular Biotechnology of the Austrian Academy of Sciences, the Helmholtz Centre for Infection Research, and the Hubrecht Institute, among others. Researchers from the University of Tokyo and the University of Cambridge also contributed to the study.

This study offers a deep understanding of the biological processes that help ensure the health of both mother and baby during pregnancy and breastfeeding and underscores the importance of the RANK/RANKL system in these critical changes.

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