Lipopolysaccharide from Crypt-Specific Core Microbiota Modulates the Colonic Epithelial Proliferation-to-Differentiation Balance
ABSTRACT 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 represe...
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American Society for Microbiology
2017
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oai:doaj.org-article:cbbfa98286cc4515950d23ffbebe82222021-11-15T15:51:51ZLipopolysaccharide from Crypt-Specific Core Microbiota Modulates the Colonic Epithelial Proliferation-to-Differentiation Balance10.1128/mBio.01680-172150-7511https://doaj.org/article/cbbfa98286cc4515950d23ffbebe82222017-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01680-17https://doaj.org/toc/2150-7511ABSTRACT 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 epithelium proliferation through necroptosis of stem cells and enhances cell differentiation, mainly the goblet cell lineage.Tomoaki NaitoCéline MuletCristina De CastroAntonio MolinaroAzadeh SaffarianGiulia NigroMarion BérardMélanie ClercAmy B. PedersenPhilippe J. SansonettiThierry PédronAmerican Society for Microbiologyarticlehomeostasisintestinal stem cellsLPSnecroptosisMicrobiologyQR1-502ENmBio, Vol 8, Iss 5 (2017) |
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homeostasis intestinal stem cells LPS necroptosis Microbiology QR1-502 |
| spellingShingle |
homeostasis intestinal stem cells LPS necroptosis Microbiology QR1-502 Tomoaki Naito Céline Mulet Cristina De Castro Antonio Molinaro Azadeh Saffarian Giulia Nigro Marion Bérard Mélanie Clerc Amy B. Pedersen Philippe J. Sansonetti Thierry Pédron Lipopolysaccharide from Crypt-Specific Core Microbiota Modulates the Colonic Epithelial Proliferation-to-Differentiation Balance |
| description |
ABSTRACT 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 epithelium proliferation through necroptosis of stem cells and enhances cell differentiation, mainly the goblet cell lineage. |
| format |
article |
| author |
Tomoaki Naito Céline Mulet Cristina De Castro Antonio Molinaro Azadeh Saffarian Giulia Nigro Marion Bérard Mélanie Clerc Amy B. Pedersen Philippe J. Sansonetti Thierry Pédron |
| author_facet |
Tomoaki Naito Céline Mulet Cristina De Castro Antonio Molinaro Azadeh Saffarian Giulia Nigro Marion Bérard Mélanie Clerc Amy B. Pedersen Philippe J. Sansonetti Thierry Pédron |
| author_sort |
Tomoaki Naito |
| title |
Lipopolysaccharide from Crypt-Specific Core Microbiota Modulates the Colonic Epithelial Proliferation-to-Differentiation Balance |
| title_short |
Lipopolysaccharide from Crypt-Specific Core Microbiota Modulates the Colonic Epithelial Proliferation-to-Differentiation Balance |
| title_full |
Lipopolysaccharide from Crypt-Specific Core Microbiota Modulates the Colonic Epithelial Proliferation-to-Differentiation Balance |
| title_fullStr |
Lipopolysaccharide from Crypt-Specific Core Microbiota Modulates the Colonic Epithelial Proliferation-to-Differentiation Balance |
| title_full_unstemmed |
Lipopolysaccharide from Crypt-Specific Core Microbiota Modulates the Colonic Epithelial Proliferation-to-Differentiation Balance |
| title_sort |
lipopolysaccharide from crypt-specific core microbiota modulates the colonic epithelial proliferation-to-differentiation balance |
| publisher |
American Society for Microbiology |
| publishDate |
2017 |
| url |
https://doaj.org/article/cbbfa98286cc4515950d23ffbebe8222 |
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