Chronic minocycline treatment exerts antidepressant effect, inhibits neuroinflammation, and modulates gut microbiota in mice

Minocycline is a second-generation, semi-synthetic tetracycline, and has broad spectrum-antibacterial activity. Interestingly, many studies have demonstrated that minocycline is beneficial for depression, which may be due to its effects on neuroinflammation modulation. Recently, gut microbiota imbalance has been found in depression patient and animal models. Based on the fact of minocycline usually acting as an antibiotic and the relationship between depression, gut microbiota, and neuroinflammation, we designed this study to detect the effects of chronic minocycline treatment on antidepression, neuroinflammation, and gut microbiota modulation. Our results showed that minocycline treatment for 4 weeks, not acute treatment, exerted antidepressant effect in mice exposed to unpredictable chronic mild stress (CUMS). Further results suggested that chronic minocycline treatment inhibited neuroinflammation of hippocampus and altered species abundance and metabolites of gut microbiota. Meantime, we found that chronic minocycline treatment ameliorated intestinal barrier disruption and reduced the bacteriological indexes, such as diamine oxidase, C-reaction protein, and endotoxin in peripheral blood of CUMS mice. To sum up, our findings confirm that chronic minocycline treatment exerts the antidepressant effect, inhibits neuroinflammation, and modulates gut microbiota. All of these imply that the antidepressant mechanism of chronic minocycline treatment is maybe due to the combined action of neuroinflammation and gut microbiota modulation, which need further prospective studies.