Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Limosilactobacillus fermentum SLAM 216-Derived Extracellular Vesicles Promote Intestinal Maturation in Mouse Organoid Models

  • Hyejin Choi (Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Science, Seoul National University) ;
  • Min-Jin Kwak (Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Science, Seoul National University) ;
  • An Na Kang (Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Science, Seoul National University) ;
  • Daye Mun (Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Science, Seoul National University) ;
  • Suengwon Lee (Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine) ;
  • Mi Ri Park (Korea Food Research Institute) ;
  • Sangnam Oh (Department of Functional Food and Biotechnology, Jeonju University) ;
  • Younghoon Kim (Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Science, Seoul National University)
  • Received : 2024.05.25
  • Accepted : 2024.07.31
  • Published : 2024.10.28
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Abstract

Probiotics, when consumed in adequate amounts, can promote the health of the host and beneficially modulate the host's immunity. Particularly during the host's early life, the gut intestine undergoes a period of epithelial maturation in which epithelial cells organize into specific crypt and villus structures. This process can be mediated by the gut microbiota. Recent studies have reported that the administration of probiotics can further promote intestinal maturation in the neonatal intestine. Therefore, in this study, we investigated the effects of extracellular vesicles derived from the Limosilactobacillus fermentum SLAM 216 strain, which is an established probiotic with known immune and anti-aging effects on intestinal epithelial maturation and homeostasis, using mouse small intestinal organoids. As per our findings, treatment with L. fermentum SLAM 216-derived LF216EV (LF216EV) has significantly increased the bud number and size of organoid buds. Furthermore, extracellular vesicle (EV) treatment upregulated the expression of maturation-related genes, including Ascl2, Ephb2, Lgr5, and Sox9. Tight junctions are known to have an important role in the intestinal immune barrier, and EV treatment has significantly increased the expression of genes associated with tight junctions, such as Claudin, Muc2, Occludin, and Zo-1, indicating that it can promote intestinal development. This was supported by RNA sequencing, which revealed the upregulation of genes associated with cAMP-mediated signaling, which is known to regulate cellular processes including cell differentiation. Additionally, organoids exposed to LF216EV exhibited upregulation of genes associated with maintaining brain memory and neurotransmission, suggesting possible future functional implications.

Keywords

Acknowledgement

This research was supported by a National Research Foundation of Korea Grant, funded by the Korean government (MEST) (NRF-2021R1A2C3011051) and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2022M3A9I5018286).

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