Erythroid differentiation regulator-1 induced by microbiota in early life drives intestinal stem cell proliferation and regeneration

Hirohito Abo, Benoit Chassaing, Akihito Harusato, Miguel Quiros, Jennifer C. Brazil, Vu L. Ngo, Emilie Viennois, Didier Merlin, Andrew T. Gewirtz, Asma Nusrat and Timothy L. Denning ()
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Hirohito Abo: Georgia State University
Benoit Chassaing: Georgia State University
Akihito Harusato: Georgia State University
Miguel Quiros: University of Michigan
Jennifer C. Brazil: University of Michigan
Vu L. Ngo: Georgia State University
Emilie Viennois: Georgia State University
Didier Merlin: Georgia State University
Andrew T. Gewirtz: Georgia State University
Asma Nusrat: University of Michigan
Timothy L. Denning: Georgia State University

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract Gut microbiota and their metabolites are instrumental in regulating intestinal homeostasis. However, early-life microbiota associated influences on intestinal development remain incompletely understood. Here we demonstrate that co-housing of germ-free (GF) mice with specific-pathogen free (SPF) mice at weaning (exGF) results in altered intestinal gene expression. Our results reveal that one highly differentially expressed gene, erythroid differentiation regulator-1 (Erdr1), is induced during development in SPF but not GF or exGF mice and localizes to Lgr5+ stem cells and transit amplifying (TA) cells. Erdr1 functions to induce Wnt signaling in epithelial cells, increase Lgr5+ stem cell expansion, and promote intestinal organoid growth. Additionally, Erdr1 accelerates scratch-wound closure in vitro, increases Lgr5+ intestinal stem cell regeneration following radiation-induced injury in vivo, and enhances recovery from dextran sodium sulfate (DSS)-induced colonic damage. Collectively, our findings indicate that early-life microbiota controls Erdr1-mediated intestinal epithelial proliferation and regeneration in response to mucosal damage.

Date: 2020
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DOI: 10.1038/s41467-019-14258-z

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