Polyphenols and Probiotics Improve Mood Disorders by Regulating the Gut-Lung Axis

Mood disorders like depression and anxiety pose a growing global health challenge, with current treatments often limited by side effects. While the gut-brain axis is well-established in emotional regulation, the emerging role of the gut-lung axis as a “second pathway” remains less clearly defined, particularly regarding how dietary components can modulate this axis to improve mood. This review aims to address this gap by systematically examining the synergistic mechanisms through which polyphenols and probiotics regulate the gut-lung axis to alleviate mood disorders. The bidirectional network connects the gut and lungs via shared mucosal immunity, microbial translocation, and inflammatory signaling. Polyphenols exert anti-inflammatory, antioxidant, and microbiota-modulating effects, with their metabolites influencing pulmonary immunity. Probiotics contribute through gut colonization, production of neuroactive substances, and modulation of lung immunity. Their combined use exhibits synergy: polyphenols act as prebiotics, enhancing probiotic growth and function. Together, they suppress inflammation-related signaling pathway, strengthen gut-lung barrier integrity, boost short-chain fatty acid production, and modulate tryptophan metabolism. This multi-layered interaction establishes a comprehensive regulatory network within the gut-lung-brain axis through immune, neuroactive, and metabolic pathways. This review proposes the gut-lung axis as a novel target for nutritional and microbiome-based interventions in mood disorders, thereby guiding clinical translation.