Impact of omega-3 fatty acids on hypertriglyceridemia, lipidomics, and gut microbiome in patients with type 2 diabetes
Jieli Lu, Ruixin Liu, Huahui Ren, Shuangyuan Wang, Chunyan Hu, Zhun Shi, Mian Li, Wei Liu, Qin Wan, Qing Su, Qifu Li, Hongting Zheng, Shen Qu, Fangming Yang, Hongyi Ji, Hong Lin, Hongyan Qi, Xueyan Wu, Kui Wu, Yuhong Chen, Yu Xu, Min Xu, Tiange Wang, Jie Zheng, Guang Ning, Ruizhi Zheng, Yufang Bi, Huanzi Zhong, Weiqing Wang
Abstract
Background Fish oil (FO), a mixture of omega-3 fatty acids mainly comprising docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), has been recommended for patients with type 2 diabetes (T2D) and hypertriglyceridemia. However, its effects on lipidomic profiles and gut microbiota and the factors influencing triglyceride (TG) reduction remain unclear. Methods We conducted a 12-week, randomized, double-blind, placebo-controlled trial in 309 Chinese patients with T2D with hypertriglyceridemia (ClinicalTrials.gov: NCT03120299 ). Participants were randomly assigned (1:1) to receive either 4 g FO or corn oil for 12 weeks. The primary outcome was changes in serum TGs and the lipidomic profile, and the secondary outcome included changes in the gut microbiome and other metabolic variables. Findings The FO group had significantly better TG reduction (mean [95% confidence interval (CI)]: −1.51 [−2.01, −1.01] mmol/L) compared to the corn oil group (−0.66 [−1.15, −0.16] mmol/L, p = 0.02). FO significantly altered the serum lipid profile by reducing low-unsaturated TG species and increasing those containing DHA or EPA. FO had minor effects on gut microbiota, while baseline microbial features predicted the TG response to FO better than phenotypic or lipidomic features, potentially mediated by specific lipid metabolites. A total of 9 lipid metabolites significantly mediated the link between 4 baseline microbial variables and the TG response to FO supplementation. Conclusions Our findings demonstrate differential impacts of omega-3 fatty acids on lipidomic and microbial profiles in T2D and highlight the importance of baseline gut microbiota characteristics in predicting the TG-lowering efficacy of FO. Funding This study was funded by the National Nature Science Foundation. • Fish oil supplementation significantly reduces serum triglycerides • Fish oil supplementation induces substantial alterations in serum lipidomic profile • Fish oil has a minor impact on gut microbial diversity and composition • Baseline gut microbiota effectively predict TG reduction in response to fish oil The impacts of fish oil supplementation on serum lipidome and gut microbiota and their effects on triglyceride response remain unclear. In this study, Lu et al. investigated the effects of fish oil on lipidomic profiles and gut microbiota in patients with type 2 diabetes and hypertriglyceridemia in a randomized, double-blind, placebo-controlled trial with 309 participants. They found that fish oil significantly reduced serum triglycerides and altered lipid profiles. Moreover, the study also demonstrated that baseline gut microbiota characteristics were more predictive of triglyceride-lowering efficacy than phenotypic or lipidomic features. The findings underscore the importance of considering gut microbiota in predicting and enhancing the therapeutic effects of fish oil in managing hypertriglyceridemia in patients with type 2 diabetes. Lu et al. demonstrate that fish oil supplementation reduces serum triglycerides and alters lipid profiles in patients with type 2 diabetes and hypertriglyceridemia. Baseline gut microbiota characteristics are stronger predictors of triglyceride response to fish oil than phenotypic or lipidomic features.