Omega-3 Polyunsaturated Fatty Acids: A Clinical Perspective on Gut Microbiota, Major Depressive Disorder, and Obesity

Major depressive disorder (MDD) and obesity are significant global health concerns with a strong bidirectional relationship. Gut microbiota dysbiosis has been implicated in both MDD and obesity, characterized by alterations in microbial diversity and its metabolites. Omega-3 polyunsaturated fatty acids (PUFAs), mainly eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) have shown promise in alleviating depressive symptoms and improving metabolic health. Diet plays a crucial role in shaping gut microbiota, with omega-3 PUFAs emerging as a potential therapeutic target. By modulating gut microbiota, reducing inflammation, and influencing neurotransmitter systems, omega-3 PUFAs may offer a novel approach to treating MDD and obesity. This article will investigate the potential role of omega-3 PUFAs in the relationship between depression and obesity via modulating the gut microbiome and reducing inflammation. Further investigation is needed to establish the optimal dosage of supplementation for individuals with MDD and comorbid obesity. [ Psychiatr Ann . 2025;55(2):e34–e39.]