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Microbiota-Derived Lactate Accelerates Intestinal Stem-Cell-Mediated Epithelial Development.

Cell host & microbe | 2018

Symbionts play an indispensable role in gut homeostasis, but underlying mechanisms remain elusive. To clarify the role of lactic-acid-producing bacteria (LAB) on intestinal stem-cell (ISC)-mediated epithelial development, we fed mice with LAB-type symbionts such as Bifidobacterium and Lactobacillus spp. Here we show that administration of LAB-type symbionts significantly increased expansion of ISCs, Paneth cells, and goblet cells. Lactate stimulated ISC proliferation through Wnt/β-catenin signals of Paneth cells and intestinal stromal cells. Moreover, Lactobacillus plantarum strains lacking lactate dehydrogenase activity, which are deficient in lactate production, elicited less ISC proliferation. Pre-treatment with LAB-type symbionts or lactate protected mice in response to gut injury provoked by combined treatments with radiation and a chemotherapy drug. Impaired ISC-mediated epithelial development was found in mice deficient of the lactate G-protein-coupled receptor, Gpr81. Our results demonstrate that LAB-type symbiont-derived lactate plays a pivotal role in promoting ISC-mediated epithelial development in a Gpr81-dependent manner.

Pubmed ID: 30543778 RIS Download

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FlowJo (tool)

RRID:SCR_008520

Software for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.

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FKSG80 / GPR81 Antibody (PE) (antibody)

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PORCN antibody (antibody)

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Wnt3 antibody (antibody)

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OLFM4 antibody (antibody)

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Beta Arrestin 2 antibody (antibody)

RRID:AB_2060273

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LYZ / Lysozyme Antibody (aa22‑143, FITC) (antibody)

RRID:AB_2753328

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Lysozyme antibody [BGN/06/961] (antibody)

RRID:AB_776115

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Wnt3a antibody (antibody)

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Lysozyme antibody [BGN/06/961] (antibody)

RRID:AB_776115

This monoclonal targets Human Lysozyme

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OLFM4 antibody (antibody)

RRID:AB_10670544

This polyclonal targets OLFM4 antibody

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Beta Arrestin 2 antibody (antibody)

RRID:AB_2060273

This monoclonal targets Beta Arrestin 2 antibody

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FKSG80 / GPR81 Antibody (PE) (antibody)

RRID:AB_2753327

This polyclonal targets FKSG80 / GPR81

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PORCN antibody (antibody)

RRID:AB_10860951

This polyclonal targets PORCN antibody

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LYZ / Lysozyme Antibody (aa22‑143, FITC) (antibody)

RRID:AB_2753328

This polyclonal targets LYZ / Lysozyme

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Wnt3a antibody (antibody)

RRID:AB_2215308

This polyclonal targets Wnt3a

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Wnt3 antibody (antibody)

RRID:AB_883541

This polyclonal targets Human Wnt3

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