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Latest Findings on the Interaction Mechanism Between Depressive Disorder and Intestinal Permeability
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摘要: 肠道屏障是由多层防御屏障组成的复合结构，能阻挡肠道、外来菌群及其代谢产物向人体内环境转移。肠道屏障的完整性可用肠道通透性来评价，在抑郁症患者中可观察到肠道通透性升高的现象。一些研究证明，抑郁症与肠道屏障存在相互作用，本文将对由抑郁症患者体内低度炎症、迷走神经功能障碍、下丘脑-垂体-肾上腺轴紊乱引起的肠道通透性改变机制，及肠道屏障破坏引起肠道微生物易位导致的抑郁症发病机制进行综述。此外，我们还将探讨抗抑郁药物改善抑郁患者肠道通透性及益生菌改善抑郁症的潜在作用机制。Abstract: The intestinal barrier, a complex structure consisting of multiple layers of defense barriers, blocks the transfer of intestinal and foreign bacteria and their metabolites into the internal environment of the human body. Intestinal permeability can be used to evaluate the integrity of the intestinal barrier. Increased intestinal permeability has been observed in patients with depressive disorder. Some studies have reported an interaction between depressive disorder and intestinal barrier. Herein, we reviewed reported findings on the mechanisms of how systematic low-grade inflammation, vagal nerve dysfunction, and hypothalamic-pituitary-adrenal axis dysfunction cause changes in intestinal permeability in patients with depressive disorder and the pathogenic mechanism of how bacterial translocation caused by damaged intestinal barrier leads to depressive disorder. In addition, the potential mechanisms of how antidepressants improve intestinal permeability and how probiotics improve depressive disorder have been discussed.
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Key words:
- Intestinal permeability /
- Depressive disorder /
- Mechanism
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图 1 抑郁症与肠道通透性相互作用机制
Figure 1. The interaction mechanism between major depressive disorder and intestinal permeability
HPA: hypothalamic-pituitary-adrenal; CRF: corticotropin releasing factor; ACTH: adrenocorticotropic hormone; GC: glucocorticoid; IFN-γ: interferon-γ; IL-1β: interleukin-1β; IL-6: interleukin-6; TNF-α: tumor necrosis factor-α. * The bidirectional arrow indicates that the low-grade inflammation of the whole body in patients with depressive disorder may come from the intestinal tract, or may be caused by other factors acting on intestinal barrier. We created the figure by using images provided by Servier Medical Art (http://smart.servier.com). Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/).
表 1 抑郁症患者肠道通透性临床研究概况
Table 1. Overview of clinical studies on intestinal permeability in MDD patients
Intestinal permeability biomarker Reference Experimental
groupControl
groupTest
sampleTest
methodResults Zonulin ALVAREZ-MON, 2019[9] MDD (n=22) HC (n=14) Serum ELISA No significant difference ALVAREZ-MON, 2021[10] MDD (n=30) HC (n=20) Serum ELISA No significant difference OHLSSON, 2019[11] MDD (n=13) HC (n=17) Plasma ELISA No significant difference WU, 2023[12] MDD (n=50) HC (n=40) Plasma ELISA Higher in MDD Intestinal fatty acid-binding protein (I-FABP) ALVAREZ-MON, 2019[9] MDD (n=22) HC (n=14) Serum ELISA Higher in MDD ALVAREZ-MON, 2021[10] MDD (n=30) HC (n=20) Serum ELISA Higher in MDD OHLSSON, 2019[11] MDD (n=13) HC (n=17) Plasma ELISA No significant difference Lipopolysaccharide-binding protein (LBP) ALVAREZ-MON, 2019[9] MDD (n=22) HC (n=14) Serum ELISA Higher in MDD ALVAREZ-MON, 2021[10] MDD (n=30) HC (n=20) Serum ELISA Higher in MDD IgM and IgA against gram-negative enterobacteria MAES, 2008[13] MDD (n=28) HC (n=23) Serum ELISA Higher in MDD MAES, 2012[14] Depression (n=112) HC (n=28) Serum ELISA Higher in depressive disorder Lactulose/Mannitol ratio (LMR) CALARGE, 2019[15] MDD (n=16) HC (n=14) Urine Liquid chromatographic analysis No significant difference MDD: major depressive disorder; HC: healthy control; ELISA: enzyme-linked immunosorbent assay; LAL: limulus amebocyte lysate. 
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