The mechanism and application prospect of intestinal flora regulating inflammatory response and oхidative stress in depression

Abstract

Depression, a prevalent mental disorder, is characterized by feelings of sadness, irritability, excessive guilt, low self-esteem, and in severe cases, hopelessness and suicidal ideation. These symptoms significantly impact the quality of life and functioning of affected individuals. Approximately 300 million people worldwide suffer from depression, leading to substantial financial and social burdens. The COVID-19 pandemic has further exacerbated the recurrence rates and prevalence of depression, emphasizing the need for effective intervention strategies. Notably, National Health and Family Planning Commission of the People’s Republic of China and other relevant authorities have prioritized the prevention and treatment of depression. Multiple studies have demonstrated a strong association between inflammation and mental health. Patients with depression often exhibit elevated levels of pro-inflammatory cytokines, such as interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor (TNF), etc. In addition, oxidative stress may be involved in the pathogenesis of depression. Patients with depression often exhibit an imbalance in oxidative stress levels. For instance, the concentration of oxidative stress markers, such as malondialdehyde, increases, whereas the activity of antioxidant enzymes, such as catalase, decreases, etc. These physiological changes compromise the integrity of the intestinal barrier and enhance the permeability of the blood-brain barrier, contributing to the occurrence and development of depression. Pharmaceutical interventions remain the cornerstone of depression management. These medications can directly impact the intestinal flora or indirectly modulate the microbial environment through their pharmacodynamic effects on the host. This modulation impacts the composition and functionality of the intestinal microbiota, ultimately affecting drug efficacy. However, long-term antidepressant use may lead to undesirable side effects, such as weight gain, excessive sweating, and sexual dysfunction. Advancements in metagenomics and metabolomics have revealed the metabolic pathways of host intestinal flora. Changes in the structure and composition of intestinal flora may play a pivotal role in the pathogenesis of depression. Experimental studies have demonstrated that in individuals with depression, there is an increase in the abundance of Bacteroidetes, which are associated with inflammation. Conversely, there is a decrease in the abundance of Firmicutes, which are associated with reducing inflammation. The intestinal flora, often referred to as “dynamic organ”, resides in the human digestive tract and significantly influences brain function and emotional well-being. The complex “gut-brain” axis maintains homeostasis and facilitates communication between the gut and the brain. Consequently, this microbiota becomes a potential target for antidepressant therapy, showing promise in alleviating and treating depression. This paper reviews the role of “gut-brain” axis in inflammation and oxidative stress in patients with depression. In addition, it emphasizes the association between antidepressants and the intestinal flora. Our study compiles various approaches for aiding in the intervention or treatment of depression through the “gut-brain” axis. These methods include dietary adjustments, probiotics, prebiotics, postbiotics, and fecal microbiota transplantation (FMT). These developments contribute to the advancement of precision medicine strategies targeting the intestinal flora in the treatment of depression.