한빛사논문
Hana Lee a§, Kwang Bo Jung a§, Ohman Kwon a§, Ye Seul Son a, Eunho Choi a,b, Won Dong Yu a,b, Naeun Son a,b, Jun Hyoung Jeon c, Hana Jo c, Haneol Yang c, Yeong Rak Son c, Chan-Seok Yun c, HyunSoo Cho b,e, Sang Kyu Kim d, Dae-Soo Kim b,e, Doo-Sang Park c, and Mi-Young Son a,b
aStem Cell Research Convergence Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea; bKRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon, Republic of Korea; cKorean Collection for Type Cultures, Biological Resource Center, KRIBB, Jeongeup, Republic of Korea; dLaboratory of Efficacy Research, Korea Ginseng Corp., Daejeon, Republic of Korea; eDigital Biotech Innovation Center, KRIBB, Daejeon, Republic of Korea
§These authors contributed equally to this work.
CONTACT Mi-Young Son; Doo-Sang Park; Dae-Soo Kim
Abstract
Little is known about the modulatory capacity of the microbiota in early intestinal development. We examined various intestinal models that respond to gut microbial metabolites based on human pluripotent stem cell-derived human intestinal organoids (hIOs): physiologically relevant in vitro fetal-like intestine, intestinal stem cell, and intestinal disease models. We found that a newly isolated Limosilactobacillus reuteri strain DS0384 accelerated maturation of the fetal intestine using 3D hIO with immature fetal characteristics. Comparative metabolomic profiling analysis revealed that the secreted metabolite N-carbamyl glutamic acid (NCG) is involved in the beneficial effect of DS0384 cell-free supernatants on the intestinal maturation of hIOs. Experiments in an intestinal stem cell spheroid model and hIO-based intestinal inflamed model revealed that the cell-free supernatant from DS0384 comprising NCG promoted intestinal stem cell proliferation and was important for intestinal protection against cytokine-induced intestinal epithelial injury. The probiotic properties of DS0384 were also evaluated, including acid and bile tolerance and ability to adhere to human intestinal cells. Seven-day oral administration of DS0384 and cell-free supernatant promoted the intestinal development of newborn mice. Moreover, NCG exerted a protective effect on experimental colitis in mice. These results suggest that DS0384 is a useful agent for probiotic applications and therapeutic treatment for disorders of early gut development and for preventing intestinal barrier dysfunction.
논문정보
관련 링크
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기