Limosilactobacillus reuteri DS0384 promotes intestinal epithelial maturation via the postbiotic effect in human intestinal organoids and infant mice

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-lik...

Full description

Saved in:
Bibliographic Details
Main Authors: Hana Lee, Kwang Bo Jung, Ohman Kwon, Ye Seul Son, Eunho Choi, Won Dong Yu, Naeun Son, Jun Hyoung Jeon, Hana Jo, Haneol Yang, Yeong Rak Son, Chan-Seok Yun, Hyun-Soo Cho, Sang Kyu Kim, Dae-Soo Kim, Doo-Sang Park, Mi-Young Son
Format: Article
Language:English
Published: Taylor & Francis Group 2022-12-01
Series:Gut Microbes
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/19490976.2022.2121580
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849763434294411264
author Hana Lee
Kwang Bo Jung
Ohman Kwon
Ye Seul Son
Eunho Choi
Won Dong Yu
Naeun Son
Jun Hyoung Jeon
Hana Jo
Haneol Yang
Yeong Rak Son
Chan-Seok Yun
Hyun-Soo Cho
Sang Kyu Kim
Dae-Soo Kim
Doo-Sang Park
Mi-Young Son
author_facet Hana Lee
Kwang Bo Jung
Ohman Kwon
Ye Seul Son
Eunho Choi
Won Dong Yu
Naeun Son
Jun Hyoung Jeon
Hana Jo
Haneol Yang
Yeong Rak Son
Chan-Seok Yun
Hyun-Soo Cho
Sang Kyu Kim
Dae-Soo Kim
Doo-Sang Park
Mi-Young Son
author_sort Hana Lee
collection DOAJ
description 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.
format Article
id doaj-art-bcedc8c3adae41f9bf2188ec7de1d48b
institution DOAJ
issn 1949-0976
1949-0984
language English
publishDate 2022-12-01
publisher Taylor & Francis Group
record_format Article
series Gut Microbes
spelling doaj-art-bcedc8c3adae41f9bf2188ec7de1d48b2025-08-20T03:05:25ZengTaylor & Francis GroupGut Microbes1949-09761949-09842022-12-0114110.1080/19490976.2022.2121580Limosilactobacillus reuteri DS0384 promotes intestinal epithelial maturation via the postbiotic effect in human intestinal organoids and infant miceHana Lee0Kwang Bo Jung1Ohman Kwon2Ye Seul Son3Eunho Choi4Won Dong Yu5Naeun Son6Jun Hyoung Jeon7Hana Jo8Haneol Yang9Yeong Rak Son10Chan-Seok Yun11Hyun-Soo Cho12Sang Kyu Kim13Dae-Soo Kim14Doo-Sang Park15Mi-Young Son16Stem Cell Research Convergence Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of KoreaStem Cell Research Convergence Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of KoreaStem Cell Research Convergence Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of KoreaStem Cell Research Convergence Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of KoreaStem Cell Research Convergence Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of KoreaStem Cell Research Convergence Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of KoreaStem Cell Research Convergence Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of KoreaKorean Collection for Type Cultures, Biological Resource Center, KRIBB, Jeongeup, Republic of KoreaKorean Collection for Type Cultures, Biological Resource Center, KRIBB, Jeongeup, Republic of KoreaKorean Collection for Type Cultures, Biological Resource Center, KRIBB, Jeongeup, Republic of KoreaKorean Collection for Type Cultures, Biological Resource Center, KRIBB, Jeongeup, Republic of KoreaKorean Collection for Type Cultures, Biological Resource Center, KRIBB, Jeongeup, Republic of KoreaKRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon, Republic of KoreaLaboratory of Efficacy Research, Korea Ginseng Corp., Daejeon, Republic of KoreaKRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon, Republic of KoreaKorean Collection for Type Cultures, Biological Resource Center, KRIBB, Jeongeup, Republic of KoreaStem Cell Research Convergence Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of KoreaLittle 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.https://www.tandfonline.com/doi/10.1080/19490976.2022.2121580Human intestinal organoidintestinal developmentepithelial maturationgut microbiotaprobioticpostbiotic
spellingShingle Hana Lee
Kwang Bo Jung
Ohman Kwon
Ye Seul Son
Eunho Choi
Won Dong Yu
Naeun Son
Jun Hyoung Jeon
Hana Jo
Haneol Yang
Yeong Rak Son
Chan-Seok Yun
Hyun-Soo Cho
Sang Kyu Kim
Dae-Soo Kim
Doo-Sang Park
Mi-Young Son
Limosilactobacillus reuteri DS0384 promotes intestinal epithelial maturation via the postbiotic effect in human intestinal organoids and infant mice
Gut Microbes
Human intestinal organoid
intestinal development
epithelial maturation
gut microbiota
probiotic
postbiotic
title Limosilactobacillus reuteri DS0384 promotes intestinal epithelial maturation via the postbiotic effect in human intestinal organoids and infant mice
title_full Limosilactobacillus reuteri DS0384 promotes intestinal epithelial maturation via the postbiotic effect in human intestinal organoids and infant mice
title_fullStr Limosilactobacillus reuteri DS0384 promotes intestinal epithelial maturation via the postbiotic effect in human intestinal organoids and infant mice
title_full_unstemmed Limosilactobacillus reuteri DS0384 promotes intestinal epithelial maturation via the postbiotic effect in human intestinal organoids and infant mice
title_short Limosilactobacillus reuteri DS0384 promotes intestinal epithelial maturation via the postbiotic effect in human intestinal organoids and infant mice
title_sort limosilactobacillus reuteri ds0384 promotes intestinal epithelial maturation via the postbiotic effect in human intestinal organoids and infant mice
topic Human intestinal organoid
intestinal development
epithelial maturation
gut microbiota
probiotic
postbiotic
url https://www.tandfonline.com/doi/10.1080/19490976.2022.2121580
work_keys_str_mv AT hanalee limosilactobacillusreuterids0384promotesintestinalepithelialmaturationviathepostbioticeffectinhumanintestinalorganoidsandinfantmice
AT kwangbojung limosilactobacillusreuterids0384promotesintestinalepithelialmaturationviathepostbioticeffectinhumanintestinalorganoidsandinfantmice
AT ohmankwon limosilactobacillusreuterids0384promotesintestinalepithelialmaturationviathepostbioticeffectinhumanintestinalorganoidsandinfantmice
AT yeseulson limosilactobacillusreuterids0384promotesintestinalepithelialmaturationviathepostbioticeffectinhumanintestinalorganoidsandinfantmice
AT eunhochoi limosilactobacillusreuterids0384promotesintestinalepithelialmaturationviathepostbioticeffectinhumanintestinalorganoidsandinfantmice
AT wondongyu limosilactobacillusreuterids0384promotesintestinalepithelialmaturationviathepostbioticeffectinhumanintestinalorganoidsandinfantmice
AT naeunson limosilactobacillusreuterids0384promotesintestinalepithelialmaturationviathepostbioticeffectinhumanintestinalorganoidsandinfantmice
AT junhyoungjeon limosilactobacillusreuterids0384promotesintestinalepithelialmaturationviathepostbioticeffectinhumanintestinalorganoidsandinfantmice
AT hanajo limosilactobacillusreuterids0384promotesintestinalepithelialmaturationviathepostbioticeffectinhumanintestinalorganoidsandinfantmice
AT haneolyang limosilactobacillusreuterids0384promotesintestinalepithelialmaturationviathepostbioticeffectinhumanintestinalorganoidsandinfantmice
AT yeongrakson limosilactobacillusreuterids0384promotesintestinalepithelialmaturationviathepostbioticeffectinhumanintestinalorganoidsandinfantmice
AT chanseokyun limosilactobacillusreuterids0384promotesintestinalepithelialmaturationviathepostbioticeffectinhumanintestinalorganoidsandinfantmice
AT hyunsoocho limosilactobacillusreuterids0384promotesintestinalepithelialmaturationviathepostbioticeffectinhumanintestinalorganoidsandinfantmice
AT sangkyukim limosilactobacillusreuterids0384promotesintestinalepithelialmaturationviathepostbioticeffectinhumanintestinalorganoidsandinfantmice
AT daesookim limosilactobacillusreuterids0384promotesintestinalepithelialmaturationviathepostbioticeffectinhumanintestinalorganoidsandinfantmice
AT doosangpark limosilactobacillusreuterids0384promotesintestinalepithelialmaturationviathepostbioticeffectinhumanintestinalorganoidsandinfantmice
AT miyoungson limosilactobacillusreuterids0384promotesintestinalepithelialmaturationviathepostbioticeffectinhumanintestinalorganoidsandinfantmice