ArticleStem cell research & therapy2023
Early weaning causes small intestinal atrophy by inhibiting the activity of intestinal stem cells: involvement of Wnt/β-catenin signaling.
Article in Stem cell research & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.
- Paneth Cells: Recent Updates on Elucidating Therapeutic Implications in Gastroenterological Disease Management.Current medicinal chemistry · 2025Pooled it
- Gut microbiota-driven IL-17/PPAR axis mediates epigallocatechin-induced intestinal repair in weaned lambs.Journal of animal science and biotechnology · 2026Article
- Microbial regulation of intestinal stem cell function: implications for alleviating intestinal injury of weaned piglets.NPJ biofilms and microbiomes · 2026Review
- Weaning Influences Epithelial Morphology, Gene Expression and Gut Microbiota Composition in Piglets.Animals : an open access journal from MDPI · 2026Article
- Kynurenine promotes porcine intestinal epithelial cell proliferation by activating the AHR-MST1-YAP1 axis.Journal of animal science and biotechnology · 2026Article
- Maternal gut microbial legacy shapes intestinal health and susceptibility of offspring to colitis.NPJ biofilms and microbiomes · 2026Article
- Medicago Sativa L. Saponin-Driven Lactobacillus Intestinalis Restores Intestinal Stemness in Naturally Aged Mice via the Bile Acid-FXR-Wnt Signaling Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEarly weaning and shorter breastfeeding duration are applied by a proportion of young mothers, especially in the social spheres of poverty-stricken areas. Early childhood is a critical period for intestinal development, which is driven by intestinal stem cells (ISCs). However, how early weaning practice affects the function of ISCs to mediate intestinal development remains unclear.
methodsWe established an excellent early weaning mice model that has significant intestinal atrophy and growth arrest symptoms to explore the responses of ISCs to early weaning. The primary and passaged intestinal organoids from the suckling or early weaning mice were cultured to explore the underlying mechanism of early weaning affecting the ISCs.
resultsEarly weaning depressed the self-renewal of ISCs and attenuated the activity of ISCs-driven intestinal epithelial regeneration and crypt expansion in vivo and ex-vivo. Further results showed that early weaning retarded the differentiation of ISCs into transit-amplifying cells and Paneth cells, and accelerated the apoptosis of villous epithelial cells, jointly leading to intestinal epithelial atrophy. Mechanistically, early weaning inhibited Wnt signaling in ISCs, while an exogenous Wnt amplifier restored ISCs' function in ex-vivo.
conclusionOur findings indicate that early weaning depresses the activity of ISCs via attenuating Wnt/β-catenin signaling and triggers the proinflammatory cytokines TNF-α, IL-1β, IL-6, and IL-17 in jejunum, thereby impeding ISCs-driven epithelial regeneration and intestinal growth, which may provide a basal theory for the development of infant nutrients targeting stem cells to alleviate early weaning-induced intestinal problems.
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Registered trials
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