Journal
GUT MICROBES
Volume 14, Issue 1, Pages -Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/19490976.2022.2121580
Keywords
Human intestinal organoid; intestinal development; epithelial maturation; gut microbiota; probiotic; postbiotic; Limosilactobacillus reuteri; N-carbamyl glutamic acid
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Funding
- National Research Foundation of Korea (NRF) - Ministry of Science, ICT and Future Planning [NRF2018M3A9H3023077, 2021M3A9H3016046]
- Korean Fund for Regenerative Medicine (KFRM) - Korea government(the Ministry of Science and ICT) [21A0404L1]
- Korean Fund for Regenerative Medicine (KFRM) - Korea government(Ministry of Health Welfare) [21A0404L1]
- Technology Innovation Program - Ministry of Trade, Industry & Energy (MOTIE, Korea) [20008777]
- Ministry of Food and Drug Safety [22213MFDS386]
- KRIBB Research Initiative Program [KGS1102113, KGM4722223, KGS1122221, KGM5232221]
- National Research Foundation of Korea [2021M3A9H3016046] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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This study investigates the modulatory capacity of a newly isolated probiotic strain (DS0384) on early intestinal development. They found that DS0384 accelerated the maturation of fetal intestines and promoted intestinal stem cell proliferation by secreting a specific metabolite (NCG). The results suggest that DS0384 has potential probiotic properties and therapeutic applications for early gut development disorders.
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.
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