Gut microbiome and glial cell dialog: Role of TCM in the treatment of depression

Depression is characterized by low mood, cognitive slowing and a tendency to self-harm, and has a complex etiology involving abnormalities in neuromodulation (e.g., monoamine transmitter imbalance and reduced neuroplasticity). Gut-brain axis studies have shown that dysregulation of gut flora can trigger neuroinflammation and impair glial cell function, leading to depression. Modulation of flora-glial cell interactions and their pharmacological mechanisms is key to treatment.

This review discusses the new discovery of the interaction mechanism between glial cells and gut microflora in depression models, providing new targets and directions for the treatment of TCM in depression. Further bridging the gap in current research on the gut-brain axis in depression.

Literature was searched, analyzed, and collected using PubMed, Web of Science, and China National Knowledge Infrastructure. The search terms used were " gut-brain axis ", " neuroinflammation ", " depression ", " glial cells ", " Gut microbiota "," TCM ", etc. Several combinations of these keywords were used. Studies using models of depression were used.

During the literature screening process, a total of 1685 records were initially retrieved from databases. After removing duplicates (1068) and other ineligible records (200), 417 articles underwent title and abstract screening, with 134 excluded. Further full-text assessment of 283 articles led to the inclusion of 149 new studies. Reasons for exclusion included mismatched outcomes (8), ineligible experimental models (12), among others. Combined with 14 previously included studies, the final review comprised 163 articles (See Figure 1). The dialog mechanism between gut microflora and glial cells plays an important role in the pathogenesis of depression. In addition, there are a variety of herbal active ingredients and herbal formulas that can significantly affect the composition of the gut flora and glial cell activation in depression models, and consequently, there is significant antidepressant potential.

Intestinal flora metabolites modulate glial cell activation, and the release of inflammatory factors by glial cells alters intestinal flora composition, both phenomena are contributory to depressive pathogenesis. In addition, we found that a variety of TCMs can improve depression based on this mechanism, providing new perspectives for clinical diagnosis and treatment of depression.