Related Experiment Video

Updated: Aug 5, 2026

Recapitulating Suckling-to-Weaning Transition In Vitro using Fetal Intestinal Organoids
08:15

Recapitulating Suckling-to-Weaning Transition In Vitro using Fetal Intestinal Organoids

Published on: November 15, 2019

Developmental factors drive the compartmentalized and discontinuous maturation of the small intestinal epithelium

Johannes Schöneich1, Aline Dupont1, Stefan Schlößer1

  • 1Institute of Medical Microbiology, RWTH Aachen University Hospital, Aachen, Germany.

Plos Biology
|August 3, 2026
PubMed

Insights

The small intestinal epithelium undergoes significant changes after birth, with development primarily driven by genetic factors rather than gut microbes. This study reveals a complex, compartmentalized maturation process in the developing gut. Keywords: small intestine, postnatal development, gut epithelium, host-microbe homeostasis.

Area of Science:

  • Developmental Biology
  • Gastroenterology
  • Immunology

Background:

  • The postnatal period is critical for small intestinal development, involving dietary transition, microbiota colonization, and immune system maturation.
  • Systematic investigation of the temporal, spatial, and cellular diversity of the small intestinal epithelium during this period is lacking.

Purpose of the Study:

  • To comprehensively analyze the developing small intestinal epithelium during the postnatal period.
  • To identify key molecular and cellular changes, and the influence of microbiota and developmental regulators.
  • To characterize age- and cell type-specific developmental trajectories and responses to infection.

Main Methods:

  • Utilized laser capture microdissection combined with bulk RNA-Seq, proteomics, and single-cell RNA-Seq.
  • Analyzed intestinal epithelium from specific pathogen-free, germ-free, and Salmonella-infected mice across the postnatal period.
  • Investigated organ site, crypt- and villus-specific expression patterns.

Main Results:

  • Revealed weak microbiota influence but strong effects of developmental regulators on early gut development.
  • Identified age-dependent signaling pathways and transcription factor activity.
  • Characterized compartmentalized maturation along the proximal-distal axis and crypt-villus axis, with discontinuous cell type profile emergence.
  • Described cell type-specific responses to neonatal enteric infection.

Conclusions:

  • The small intestinal epithelium plays an integral role in postnatal mucosal tissue maturation.
  • Findings highlight the complex, compartmentalized nature of gut development and the establishment of host-microbe homeostasis.
  • Developmental regulators, not microbiota, are the primary drivers of early postnatal gut epithelial development.

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