Southwest United Graduate School, Yunnan Key Laboratory of Cell Metabolism and Diseases, State Key Laboratory of Conservation and Utilization of Bio-resources in Yunnan, Center for Life Sciences, School of Life Sciences, Yunnan University, Kunming, China.
Elife. 2024 Oct 7;13:RP92994. doi: 10.7554/eLife.92994.
The balanced gut microbiota in intestinal mucus layer plays an instrumental role in the health of the host. However, the mechanisms by which the host regulates microbial communities in the mucus layer remain largely unknown. Here, we discovered that the host regulates bacterial colonization in the gut mucus layer by producing a protein called Chitinase 3-like protein 1 (Chi3l1). Intestinal epithelial cells are stimulated by the gut microbiota to express Chi3l1. Once expressed, Chi3l1 is secreted into the mucus layer where it interacts with the gut microbiota, specifically through a component of bacterial cell walls called peptidoglycan. This interaction between Chi3l1 and bacteria is beneficial for the colonization of bacteria in the mucus, particularly for Gram-positive bacteria like . Moreover, a deficiency of Chi3l1 leads to an imbalance in the gut microbiota, which exacerbates colitis induced by dextran sodium sulfate. By performing fecal microbiota transplantation from Villin-cre mice or replenishing in IEC mice, we were able to restore their colitis to the same level as that of Villin-cre mice. In summary, this study shows a 'scaffold model' for microbiota homeostasis by interaction between intestinal Chi3l1 and bacteria cell wall interaction, and it also highlights that an unbalanced gut microbiota in the intestinal mucus contributes to the development of colitis.
肠道黏液层中平衡的肠道微生物群在宿主健康中起着重要作用。然而，宿主调节黏液层中微生物群落的机制在很大程度上尚不清楚。在这里，我们发现宿主通过产生一种叫做几丁质酶 3 样蛋白 1（Chi3l1）的蛋白质来调节肠道黏液层中的细菌定植。肠道上皮细胞受到肠道微生物群的刺激而表达 Chi3l1。一旦表达，Chi3l1 就会被分泌到黏液层中，在那里它与肠道微生物群相互作用，特别是通过细菌细胞壁的一个成分——肽聚糖。Chi3l1 与细菌之间的这种相互作用有利于细菌在黏液中的定植，特别是有利于革兰氏阳性菌，如 。此外，Chi3l1 的缺乏会导致肠道微生物群失衡，从而加剧葡聚糖硫酸钠诱导的结肠炎。通过进行 Villin-cre 小鼠的粪便微生物群移植或补充 IEC 小鼠中的 ，我们能够将其结肠炎恢复到与 Villin-cre 小鼠相同的水平。总之，这项研究通过肠道 Chi3l1 与细菌细胞壁相互作用之间的相互作用，展示了一种微生物群稳态的“支架模型”，并强调了肠道黏液中失衡的肠道微生物群有助于结肠炎的发展。
