Innate Immunity Laboratory, Graduate School of Life Science, Hokkaido University, Sapporo, Japan.
Department of Cell Biological Science, Faculty of Advanced Life Science, Hokkaido University, Sapporo, 001-0021, Japan.
Sci Rep. 2021 May 10;11(1):9915. doi: 10.1038/s41598-021-89308-y.
Psychological stress has been reported to relate to dysbiosis, imbalance of the intestinal microbiota composition, and contribute to the onset and exacerbation of depression, though, underlying mechanisms of psychological stress-related dysbiosis have been unknown. It has been previously established that α-defensins, which are effector peptides of innate enteric immunity produced by Paneth cells in the small intestine, play an important role in regulation of the intestinal microbiota. However, the relationship between disruption of intestinal ecosystem and α-defensin under psychological stress is yet to be determined. Here we show using chronic social defeat stress (CSDS), a mouse depression model that (1) the exposure to CSDS significantly reduces α-defensin secretion by Paneth cells and (2) induces dysbiosis and significant composition changes in the intestinal metabolites. Furthermore, (3) they are recovered by administration of α-defensin. These results indicate that α-defensin plays an important role in maintaining homeostasis of the intestinal ecosystem under psychological stress, providing novel insights into the onset mechanism of stress-induced depression, and may further contribute to discovery of treatment targets for depression.
心理压力被报道与肠道菌群失调、肠道微生物组成失衡有关，并可能导致抑郁的发生和加重，尽管心理压力相关的肠道菌群失调的潜在机制尚不清楚。先前已经确定，α-防御素是小肠潘氏细胞产生的先天肠内免疫的效应肽，在调节肠道微生物群方面发挥着重要作用。然而，心理应激下肠道生态系统与α-防御素之间的关系尚待确定。在这里，我们使用慢性社交挫败应激（CSDS），一种小鼠抑郁模型，表明：（1）暴露于 CSDS 会显著降低潘氏细胞的α-防御素分泌；（2）导致肠道代谢物的菌群失调和显著组成变化；（3）α-防御素可使其恢复。这些结果表明，α-防御素在心理应激下维持肠道生态系统的平衡中起着重要作用，为应激诱导抑郁的发病机制提供了新的见解，并可能有助于发现治疗抑郁症的靶点。
