Mitochondria of intestinal epithelial cells in depression: Are they at a crossroads of gut-brain communication?

• Published in: Neuroscience and biobehavioral reviews 2023-10, Vol.153, p.105403-105403, Article 105403
• Main Authors: Wang, Yi, Lai, Han, Zhang, Tian, Wu, Jing, Tang, Huiling, Liang, Xuanwei, Ren, Dandan, Huang, Jinzhu, Li, Weihong
• Format: Article
• Language: English
• Subjects: Depression; Gut microbiota; Gut-brain axis; Intestinal epithelial cells; Mitochondria
• ISSN: 0149-7634; 1873-7528
• DOI: 10.1016/j.neubiorev.2023.105403

The role of gut dysbiosis in depression is well established. However, recent studies have shown that gut microbiota is regulated by intestinal epithelial cell (IEC) mitochondria, which has yet to receive much attention. This review summarizes the recent developments about the critical role of IEC mitochondria in actively maintaining gut microbiota, intestinal metabolism, and immune homeostasis. We propose that IEC mitochondrial dysfunction alters gut microbiota composition, participates in cell fate, mediates oxidative stress, activates the peripheral immune system, causes peripheral inflammation, and transmits peripheral signals through the vagus and enteric nervous systems. These pathological alterations lead to brain inflammation, disruption of the blood-brain barrier, activation of the hypothalamic-pituitary-adrenal axis, activation of microglia and astrocytes, induction of neuronal loss, and ultimately depression. Furthermore, we highlight the prospect of treating depression through the mitochondria of IECs. These new findings suggest that the mitochondria of IECs may be a newly found important factor in the pathogenesis of depression and represent a potential new strategy for treating depression. [Display omitted] •Mitochondrial dysfunction of intestinal epithelial cells leads to gut microbiota dysbiosis.•Mitochondria of intestinal epithelial cells may be a newly-found important factor in the pathogenesis of depression.•Protection of the mitochondrial function of intestinal epithelial cells serves as a potential new strategy for treating depression.