1State Key Laboratory of Medicinal Chemical Biology, Nankai University, 300071 Tianjin, China.
2Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, 300071 Tianjin, China.
Commun Biol. 2019 May 8;2:171. doi: 10.1038/s42003-019-0424-4. eCollection 2019.
Gut mucosal layers are crucial in maintaining the gut barrier function. Gut microbiota regulate homeostasis of gut mucosal layer via gut immune cells such as RORγt (+) IL-22(+) ILC3 cells, which can influence the proliferation of mucosal cells and the production of mucin. However, it is unclear how gut microbiota execute this regulation. Here we show that lactobacilli promote gut mucosal formation by producing L-Ornithine from arginine. L-Ornithine increases the level of aryl hydrocarbon receptor ligand L-kynurenine produced from tryptophan metabolism in gut epithelial cells, which in turn increases RORγt (+)IL-22(+) ILC3 cells. Human REG3A transgenic mice show an increased proportion of L-Ornithine producing lactobacilli in the gut contents, suggesting that gut epithelial REG3A favors the expansion of L-Ornithine producing lactobacilli. Our study implicates the importance of a crosstalk between arginine metabolism in Lactobacilli and tryptophan metabolism in gut epithelial cells in maintaining gut barrier.
肠道黏膜层对于维持肠道屏障功能至关重要。肠道微生物群通过肠道免疫细胞（如 RORγt(+)IL-22(+)ILC3 细胞）来调节肠道黏膜层的稳态，这些细胞可以影响黏膜细胞的增殖和黏蛋白的产生。然而，目前尚不清楚肠道微生物群如何执行这种调节。在这里，我们发现乳杆菌通过从精氨酸中产生 L-鸟氨酸来促进肠道黏膜的形成。L-鸟氨酸增加了色氨酸代谢产生的芳香烃受体配体 L-犬尿氨酸在肠道上皮细胞中的水平，进而增加了 RORγt(+)IL-22(+)ILC3 细胞的数量。人类 REG3A 转基因小鼠的肠道内容物中 L-鸟氨酸产生的乳杆菌比例增加，表明肠道上皮细胞 REG3A 有利于 L-鸟氨酸产生的乳杆菌的扩张。我们的研究表明，在维持肠道屏障方面，乳杆菌中的精氨酸代谢和肠道上皮细胞中的色氨酸代谢之间的相互作用非常重要。
