Are conventional antidepressants enough? The gut microbiome and nanocarrier-based delivery systems as future prospects for depression treatment.

Depression is the leading cause of disability worldwide and thus a major contributor to the economic burden of disease. In addition to genetic and epigenetic factors, sustained psychological stress linked to modern lifestyles (often characterized by high social expectations, elevated workload and increasing financial needs) may trigger psychiatric diseases such as depression. The effective treatment of this psychiatric condition represents one of the major challenges of our time, due to its skyrocketing increase in prevalence. While conventional antidepressants often provide low response rates and have frequent adverse effects, emerging research is revealing novel and more efficient therapeutic approaches. Notably, the bacteria that populates our intestinal tract, also known as the gut microbiota, is highly susceptible to stress and other factors associated with depression. Therefore, gut microbiota-targeting interventions based on lifestyle modifications or direct supplementation with biotherapeutic agents are being proposed as monotherapy or as adjuvants to conventional treatments. In addition, novel delivery systems, such as nanocarriers, for current antidepressants are being explored to improve drug bioavailability and therapeutic efficiency. This review summarizes the role of the gut microbiota in the pathogenesis of depression and its link with current antidepressant treatments. Furthermore, it explores how strategies like nanoparticle-based delivery systems are paving the way for the next generation of treatments.