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Interaction between dietary omega‐3 polyunsaturated fatty acids, obesity and gut microbiota in preclinical models: A systematic review of randomized controlled trials

Bing Cao, Yu-Tong Sun, Chifong Lam, Yalin Chen, Christine Dri, R. McIntyre

Diabetes, obesity and metabolism, 2025

12 citations

Abstract

Emerging research underscores the potential of omega‐3 polyunsaturated fatty acids (PUFAs) in weight reduction and modulation of the gut microbiota. The current review systematically examines the effects of omega‐3 PUFA supplementation on body weight regulation and gut microbiota modulation in high‐fat diet (HFD)‐induced obesity models. The study protocol was registered with PROSPERO (CRD42024559835). Systematic searches were conducted from database inception to May 2025 on PubMed/Embase, Web of Science and selected reference lists. A total of 32 trials were included, with 25 studies employing a HFD along with dietary omega‐3 PUFA supplementation and 7 studies with a HFD prior to dietary omega‐3 PUFA supplementation. Omega‐3 PUFA interventions consistently demonstrated attenuation of HFD‐induced weight gain and adiposity, though body weight remained elevated compared to low‐fat diet controls. Omega‐3 PUFA supplementation also induced significant gut microbiota compositional changes. Specifically, omega‐3 PUFAs effectively reduced the Firmicutes/Bacteroidetes (F/B) ratio, reversing a hallmark feature of HFD‐induced dysbiosis. Enrichment of beneficial taxa, such as Akkermansia muciniphila, Bifidobacterium and Lactobacillus, was consistently observed, correlating with enhanced short‐chain fatty acid (SCFA) production, improved gut barrier integrity and reduced systemic inflammation. Concurrently, omega‐3 PUFAs suppressed pathogenic bacteria, such as Desulfovibrio and…

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