Dietary polyphenols as modulators of the microbiota–gut–brain axis in depression and anxiety: a preclinical perspective

Abstract

Mood and anxiety disorders are increasingly prevalent conditions, and growing evidence indicates that the gut microbiota plays a central role in their pathophysiology through the microbiota–gut–brain axis. This review summarizes the current preclinical evidence of the effects of dietary polyphenols on this axis and their implications for mood regulation, while also discussing their translational relevance based on human-equivalent dose estimations and available clinical findings. Overall, the literature supports that polyphenols modulate the gut microbial composition and diversity, promote beneficial bacterial groups, and alter microbiota-derived metabolites, particularly short-chain fatty acids, while improving the gut barrier integrity and reducing systemic and neuroinflammatory processes. These microbiota-related changes were often associated with alterations in neurotransmitter systems, neurotrophic factors, and markers of synaptic plasticity, resulting in improvements in depressive- and anxiety-like behaviors and, in some cases, cognitive performance in animal models. Correlation analyses further strengthen the links between specific microbial taxa, metabolites, and neurobehavioral outcomes, reinforcing the relevance of gut microbiota modulation as a determinant pathway. In addition, dose translation analyses reveal substantial variability in dietary feasibility, and clinical studies, although limited, generally support beneficial effects on mood-related outcomes. Collectively, these findings highlight dietary polyphenols as promising modulators of the microbiota–gut–brain axis and emphasize their relevance for future nutritional strategies targeting mood-related disorders.