Establishment of an Apical-Out Organoid Model for Directly Assessing the Function of Postbiotics
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
In vitro organoids that mimic the physiological properties of in vivo organs based on threedimensional cell cultures overcome the limitations of two-dimensional culture systems. However, because the lumen of a typical intestinal organoid is internal, we used an apical-out intestinal organoid model in which the lumen that absorbs nutrients is outside to directly assess the function of postbiotics. A composite culture supernatant of Lactiplantibacillus plantarum KM2 and Bacillus velezensis KMU01 was used as a postbiotic treatment. Expression of COX-2 decreased in apical-out organoids co-treated with a lipopolysaccharide (LPS) and postbiotics. Expression of tight-junction markers such as ZO-1, claudin, and Occludin increased, and expression of mitochondrial homeostasis factors such as PINK1, parkin, and PGC1a also increased. As a result, small and large intestine organoids treated with postbiotics protected tight junctions from LPS-induced damage and maintained mitochondrial homeostasis through mitophagy and mitochondrial biogenesis. This suggests that an apical-out intestinal organoid model can confirm the function of food ingredients.
Abstract
In vitro organoids that mimic the physiological properties of in vivo organs based on threedimensional cell cultures overcome the limitations of two-dimensional culture systems. However, because the lumen of a typical intestinal organoid is internal, we used an apical-out intestinal organoid model in which the lumen that absorbs nutrients is outside to directly assess the function of postbiotics. A composite culture supernatant of Lactiplantibacillus plantarum KM2 and Bacillus velezensis KMU01 was used as a postbiotic treatment. Expression of COX-2 decreased in apical-out organoids co-treated with a lipopolysaccharide (LPS) and postbiotics. Expression of tight-junction markers such as ZO-1, claudin, and Occludin increased, and expression of mitochondrial homeostasis factors such as PINK1, parkin, and PGC1a also increased. As a result, small and large intestine organoids treated with postbiotics protected tight junctions from LPS-induced damage and maintained mitochondrial homeostasis through mitophagy and mitochondrial biogenesis. This suggests that an apical-out intestinal organoid model can confirm the function of food ingredients.
참고문헌 (25)
- Salim SaY, "Importance of disrupted intestinal barrier in inflammatory bowel diseases", Inflamm. Bowel Dis, 17, pp.362~381 (2011)
- Slifer ZM, "The integral role of tight junction proteins in the repair of injured intestinal epithelium", Int. J. Mol. Sci, 21, pp.972~ (2020)
- Lei S, "Somatostatin ameliorates lipopolysaccharide-induced tight junction damage via the ERK-MAPK pathway in caco2 cells", Eur. J. Cell Biol, 93, pp.299~307 (2014)
- Zhu W, "Interaction between mitochondrial homeostasis and barrier function in lipopolysaccharide-induced endothelial cell injury", Int. J. Exp. Pathol, 104, pp.272~282 (2023)
- Rath E, "Mitochondrial function—gatekeeper of intestinal epithelial cell homeostasis", Nat. Rev. Gastroenterol. Hepatol, 15, pp.497~516 (2018)
- Cunningham KE, "Peroxisome proliferator-activated receptor-γ coactivator 1-α(PGC1α)protects against experimental murine colitis", J. Biol. Chem, 291, pp.10184~10200 (2016)
- Wei H, "Selective removal of mitochondria via mitophagy : distinct pathways for different mitochondrial stresses", Biochim. Biophys. Acta Mol. Cell Res, 1853, pp.2784~2790 (2015)
- Palikaras K, "Mitochondrial homeostasis : the interplay between mitophagy and mitochondrial biogenesis", Exp. Gerontol, 56, pp.182~188 (2014)
- Żółkiewicz J, "Postbiotics—a step beyond pre-and probiotics", Nutrients, 12, pp.2189~ (2020)
- Mayorgas A, "Microbial metabolites, postbiotics, and intestinal epithelial function", Mol. Nutr. Food Res, 65, pp.2000188~ (2021)
- Gjorevski N, "Designer matrices for intestinal stem cell and organoid culture", Nature, 539, pp.560~564 (2016)
- Zhao Z, "Organoids", Nat. Rev. Methods Primers, 2, pp.94~ (2022)
- Li Y, "Next-generation porcine intestinal organoids : an apical-out organoid model for swine enteric virus infection and immune response investigations", J. Virol, 94, pp.e01006-01020~ (2020)
- Heo S, "Complete genome sequence of Lactiplantibacillus plantarum KM2 from lowtemperature aging beef", Korean J. Microbiol, 57, pp.303~306 (2021)
- Heo S, "Functional annotation genome unravels potential probiotic Bacillus velezensis strain KMU01 from traditional Korean fermented kimchi", Foods, 10, pp.563~ (2021)
- Wen X, "Role of mitophagy in regulating intestinal oxidative damage", Antioxidants, 12, pp.480~ (2023)
- Campbell HK, "Interplay between tight junctions & adherens junctions", Exp. Cell Res, 358, pp.39~44 (2017)
- dos Santos Freitas A, "Exploring the antiinflammatory effects of postbiotic proteins from Lactobacillus delbrueckii CIDCA 133 on inflammatory bowel disease model", Int J. Biol. Macromol, 277, pp.134216~ (2024)
- Compare D, "Lactobacillus casei DG and its postbiotic reduce the inflammatory mucosal response : an ex-vivo organ culture model of post-infectious irritable bowel syndrome", BMC Gastroenterol, 17, pp.53~ (2017)
- Zhang X, "Postbiotics derived from Lactobacillus plantarum 1.0386 ameliorate lipopolysaccharide-induced tight junction injury via MicroRNA-200c-3p mediated activation of the MLCK-MLC pathway in Caco-2 cells", Food Funct, 13, pp.11008~11020 (2022)
- Gao J, "A novel postbiotic from Lactobacillus rhamnosus GG with a beneficial effect on intestinal barrier function", Front. Microbiol, 10, pp.477~ (2019)
- Popov LD, "Mitochondrial biogenesis : an update", J. Cell. Mol. Med, 24, pp.4892~4899 (2020)
- Jin SM, "PINK1-and Parkin-mediated mitophagy at a glance", J. Cell Sci, 125, pp.795~799 (2012)
- Bingol B, "Mechanisms of mitophagy : PINK1, Parkin, USP30 and beyond", Free Radical Biol. Med, 100, pp.210~222 (2016)
- Ploumi C, "Mitochondrial biogenesis and clearance : a balancing act", FEBS J, 284, pp.183~195 (2017)