Gut microbiota and late-life depression: from mechanistic insights to clinical rehabilitation

Emerging evidence identifies the gut microbiota as a promising therapeutic target for late-life depression, yet its mechanisms and clinical applications remain insufficiently defined in aging populations. This review synthesizes findings from animal studies and clinical trials to examine how the gut microbiota contributes to late-life depression and to evaluate potential intervention. We first outline the association between microbial ecosystem alterations and mental health, emphasizing their relevance for late-life depression. Mechanistic pathways are then discussed in sequence: disruption of intestinal microbial networks that impair barrier integrity, dysregulation of microbial metabolites that disturb gut-brain communication, and maladaptive immune activation and signal transduction at the host-microbe interface. Building on these insights, we assess the therapeutic approaches, including dietary interventions, probiotics, prebiotics, postbiotics, and fecal microbiota transplantation. Recovery outcomes are also summarized, covering microbial composition, metabolite changes, neurological biomarkers and neuroimaging findings. Finally, we address major translational challenges, including individual variability, dynamic monitoring, technological limitations, and safety concerns. We highlight the methodological gaps that limit current research and propose future directions to advance mechanistic understanding and clinical translation. By integrating ecological balance with personalized strategies, gut microbiota-based interventions hold potential to improve prevention and treatment of late-life depression.