Lipopolysaccharide from Crypt-Specific Core Microbiota Modulates the Colonic Epithelial Proliferation-to-Differentiation Balance - Institut Pasteur Accéder directement au contenu
Article Dans Une Revue mBio Année : 2017

Lipopolysaccharide from Crypt-Specific Core Microbiota Modulates the Colonic Epithelial Proliferation-to-Differentiation Balance

Résumé

We identified a crypt-specific core microbiota (CSCM) dominated by strictly aerobic, nonfermentative bacteria in murine cecal and proximal colonic (PC) crypts and hypothesized that, among its possible functions, it may affect epithelial regeneration. In the present work, we isolated representative CSCM strains using selective media based upon our initial 16S rRNA-based molecular identification (i.e., Acinetobacter, Delftia, and Stenotrophomonas). Their tropism for the crypt was confirmed , and their influence on epithelial regeneration was demonstrated in vivo by monocolonization of germfree mice. We also showed that lipopolysaccharide (LPS), through its endotoxin activity, was the dominant bacterial agonist controlling proliferation. The relevant molecular mechanisms were analyzed using colonic crypt-derived organoids exposed to bacterial sonicates or highly purified LPS as agonists. We identified a Toll-like receptor 4 (TLR4)-dependent program affecting crypts at different stages of epithelial differentiation. LPS played a dual role: it repressed cell proliferation through RIPK3-mediated necroptosis of stem cells and cells of the transit-amplifying compartment and concurrently enhanced cell differentiation, particularly the goblet cell lineage. IMPORTANCE The LPS from crypt-specific core microbiota controls intestinal epi-thelium proliferation through necroptosis of stem cells and enhances cell differentiation , mainly the goblet cell lineage.
Fichier principal
Vignette du fichier
mBio-2017-Naito-.pdf (2.21 Mo) Télécharger le fichier
Origine : Publication financée par une institution
Loading...

Dates et versions

pasteur-01680337 , version 1 (10-01-2018)

Licence

Paternité

Identifiants

Citer

Tomoaki Naito, Céline Mulet, Cristina de Castro, Antonio Molinaro, Azadeh Saffarian, et al.. Lipopolysaccharide from Crypt-Specific Core Microbiota Modulates the Colonic Epithelial Proliferation-to-Differentiation Balance. mBio, 2017, 8 (5), ⟨10.1128/mBio.01680-17⟩. ⟨pasteur-01680337⟩
206 Consultations
137 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More