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

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dc.contributor.authorLee Y.-S.-
dc.contributor.authorKim T.-Y.-
dc.contributor.authorKim Y.-
dc.contributor.authorLee S.-H.-
dc.contributor.authorKim S.-
dc.contributor.authorKang S.W.-
dc.contributor.authorYang J.-Y.-
dc.contributor.authorBaek I.-J.-
dc.contributor.authorSung Y.H.-
dc.contributor.authorPark Y.-Y.-
dc.contributor.authorHwang S.W.-
dc.contributor.authorEunju O.-
dc.contributor.authorKwangsoon Kim-
dc.contributor.authorLiu S.-
dc.contributor.authorKamada N.-
dc.contributor.authorGao N.-
dc.contributor.authorKweon M.-N.-
dc.description.abstractSymbionts 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/��-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. Lee et al. reveal how lactic-acid-producing bacteria, including Bifidobacterium and Lactobacillus spp., support intestinal epithelial cell regeneration. Symbiont-derived lactate is sensed by G-protein-coupled receptor 81 on Paneth and stromal cells to promote regeneration in a Wnt3/ ��-catenin-dependent manner. Lactate pre-administration protects mice exposed to radiation- and chemotherapy-induced intestinal damage. ? 2018 Elsevier Inc-
dc.publisherCELL PRESS-
dc.titleMicrobiota-Derived Lactate Accelerates Intestinal Stem-Cell-Mediated Epithelial Development-
dc.contributor.affiliatedAuthorEunju O.-
dc.contributor.affiliatedAuthorKwangsoon Kim-
dc.identifier.bibliographicCitationCELL HOST & MICROBE, v.24, no.6, pp.833 - 8.46E+08-
Appears in Collections:
Academy of Immunology and Microbiology(면역 미생물 공생 연구단) > Journal Papers (저널논문)
Center for Self-assembly and Complexity(복잡계 자기조립 연구단) > Journal Papers (저널논문)
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