biostudies-literatureUnknown12Han Q<h4>Background</h4>Polyunsaturated fatty acids (PUFAs), particularly ω-3 PUFAs, can improve sepsis prognosis. However, the relationship between the pre-infection levels of PUFAs and sepsis risk remains unclear.<h4>Methods</h4>We conducted a two-sample Mendelian randomization (MR) analysis using UK Biobank data to explore the causal association between circulating unsaturated fatty acids (UFAs) and sepsis susceptibility, complemented by a sepsis mouse model (cecal ligation and puncture, CLP) for validation.<h4>Results</h4>MR analysis revealed that ω-3 PUFAs (OR: 0.912, <i>p</i> = 0.005), ω-6 PUFAs (OR: 0.914, <i>p</i> = 0.036), total PUFAs (OR: 0.894, <i>p</i> = 0.003), and the PUFAs/MUFAs (monounsaturated fatty acids) ratio (OR: 0.927, <i>p</i> = 0.042) correlated with a reduced risk of seFrontiers in medicine1701207https://www.ebi.ac.uk/biostudies/studies/S-EPMC12834780biostudies-literatureProtective impact of circulating ω-3 PUFAs on sepsis susceptibility through <i>PCSK9</i> variant: evidence from Mendelian randomization and animal experiments.PMC12834780Han QHe SLi ZSong QfalseProtective impact of circulating ω-3 PUFAs on sepsis susceptibility through <i>PCSK9</i> variant: evidence from Mendelian randomization and animal experiments.<h4>Background</h4>Polyunsaturated fatty acids (PUFAs), particularly ω-3 PUFAs, can improve sepsis prognosis. However, the relationship between the pre-infection levels of PUFAs and sepsis risk remains unclear.<h4>Methods</h4>We conducted a two-sample Mendelian randomization (MR) analysis using UK Biobank data to explore the causal association between circulating unsaturated fatty acids (UFAs) and sepsis susceptibility, complemented by a sepsis mouse model (cecal ligation and puncture, CLP) for validation.<h4>Results</h4>MR analysis revealed that ω-3 PUFAs (OR: 0.912, <i>p</i> = 0.005), ω-6 PUFAs (OR: 0.914, <i>p</i> = 0.036), total PUFAs (OR: 0.894, <i>p</i> = 0.003), and the PUFAs/MUFAs (monounsaturated fatty acids) ratio (OR: 0.927, <i>p</i> = 0.042) correlated with a reduced risk of se2025-01-01T00:00:00Z20252026-06-13T03:19:18.855Z2026-06-13T03:09:20.358ZS-EPMC128347804160845910.3389/fmed.2025.1701207