Early-life colonization by enterotoxigenic Bacteroides fragilis remodels gut epithelial stem cell states to drive colorectal cancer susceptibility
- 1Washington University in St. Louis School of Medicine
Abstract
Early-life microbial exposures can shape lifelong disease risk, yet how developmental timing influences the host-microbe interaction remains unclear. During neonatal colonization by enterotoxigenic Bacteroides fragilis (ETBF), the metalloprotease toxin BFT enables lamina propria niche entry and remodeling of colonic epithelial cell states. Early-life ETBF exposure expands murine Lgr5+ stem cells, enhances Atoh1+ secretory differentiation, and induces distal colon-specific Wnt hyperactivation. These epithelial alterations coincide with increased formation of precancerous lesions in ApcMin/+ mice. ETBF preferentially forms intracellular bacterial aggregates within these lesions, establishing a persistent reservoir that reinforces epithelial remodeling. Colonization with non-toxigenic B. fragilis during this critical developmental window prevents lesion formation, revealing that developmental context dictates whether microbial colonization imprints protection or predisposition toward colorectal cancer.
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BibTeX
@misc{russell2026earlylife,
title = {{Early-life colonization by enterotoxigenic Bacteroides fragilis remodels gut epithelial stem cell states to drive colorectal cancer susceptibility}},
author = {S. K. Russell and E. Valguarnera and J. J. Pak and J. Bubeck Wardenburg},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.28.755180},
url = {https://www.biorxiv.org/content/10.64898/2026.09.28.755180v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Early-life colonization by enterotoxigenic Bacteroides fragilis remodels gut epithelial stem cell states to drive colorectal cancer susceptibility
AU - S. K. Russell
AU - E. Valguarnera
AU - J. J. Pak
AU - J. Bubeck Wardenburg
PY - 2026
DA - 2026/09/28
PB - bioRxiv
DO - 10.64898/2026.09.28.755180
UR - https://www.biorxiv.org/content/10.64898/2026.09.28.755180v1
AB - Early-life microbial exposures can shape lifelong disease risk, yet how developmental timing influences the host-microbe interaction remains unclear. During neonatal colonization by enterotoxigenic Bacteroides fragilis (ETBF), the metalloprotease toxin BFT enables lamina propria niche entry and remodeling of colonic epithelial cell states. Early-life ETBF exposure expands murine Lgr5+ stem cells, enhances Atoh1+ secretory differentiation, and induces distal colon-specific Wnt hyperactivation. These epithelial alterations coincide with increased formation of precancerous lesions in ApcMin/+ mice. ETBF preferentially forms intracellular bacterial aggregates within these lesions, establishing a persistent reservoir that reinforces epithelial remodeling. Colonization with non-toxigenic B. fragilis during this critical developmental window prevents lesion formation, revealing that developmental context dictates whether microbial colonization imprints protection or predisposition toward colorectal cancer.
ER -