High ω6/ω3 polyunsaturated fatty acid (PUFA) ratio impairs intestinal mucosal barrier function via ROS/TLR4/NF-κB-mediated aberrant expression of tight junction proteins

Abstract

Imbalanced dietary fatty acid consumption, particularly the ω6/ω3 polyunsaturated fatty acid (PUFA) ratio, is a key factor contributing to metabolic disorders, with the intestinal barrier playing a crucial role in this process. ω6 and ω3 PUFAs are essential for human health; however, the effects of different ω6/ω3 PUFA ratios on the intestinal mucosal barrier remain poorly understood. In this study, an intestinal barrier model was established using Caco-2 cells to investigate the effects of low (1:1), medium (5:1), and high (15:1) ω6/ω3 PUFA ratios on intestinal barrier function, with comparisons made to negative control (NC) group. The results demonstrated that treatment with the high ω6/ω3 PUFA ratio (15:1) significantly increased the production of reactive oxygen species (ROS) in the cell model, leading to enhanced oxidative stress. Additionally, activation of the toll-like receptor 4/nuclear factor kappa-B (TLR4/NF-κB) inflammatory pathway was observed, exacerbating the inflammatory response and promoting the accumulation of pro-inflammatory factors, including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Furthermore, the expression of tight junction proteins was inhibited, compromising the integrity of the Caco-2 cell model. These findings indicated that long-term consumption of excessive ω6 PUFAs and insufficient ω3 PUFAs (ω6/ω3 > 5:1) may impair intestinal barrier function and increase the risk of chronic metabolic diseases. This study elucidated a potential mechanism by which the high ω6/ω3 PUFA ratio disrupted intestinal barrier function, providing insights into the importance of balanced intake of dietary fats.