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The differential effects of omega-6 and omega-3 polyunsaturated fatty acids on intestinal microbial ecology and host redox responses Rajendiran, Ethendhar

Abstract

The gastrointestinal tract harbors complex bacteria which plays an important role in health and disease. Gut microbial antigens, in conjunction with ingested dietary components, are important in intestinal immune homeostasis. High omega-6 polyunsaturated fatty acid (n6 PUFA) can induce oxidative stress and inflammation in the gut. In contrast, omega-3 (n3 PUFAs) supplementation can cure several inflammatory diseases. However, the relationship between dietary PUFAs and the intestinal microbiota remain unknown. Our study was to determine the effect of high fat diets with varying n6 and n3 PUFA on mice microbiota and host responses. We used 20% wt/wt corn oil (high n6 PUFA), corn + fish oil (19% wt/wt corn oil added to 1% wt/wt fish oil; high n6 PUFA + long chain n3 PUFA), 20% wt/wt canola oil (low n6 PUFA) as diets keeping 5% wt/wt corn oil as a chow control. After feeding mice the high fat diets for 5 weeks, Quantitative Polymerase Chain Reaction (qPCR) was used to examine the gut microbiota.Immunofluorescence was carried out to examine immune and redox responses. All high fat diets,regardless of composition, significantly reduced Bacteroides spp. and increased in intestinal epithelial cell death. Mice fed 20% corn oil had high levels of bacteria from the Clostridium and Enterobacteriaceae; associated with inflammatory bowel disease (IBD). In contrast, mice fed corn oil diets supplemented with fish oil, had enriched beneficial microbe Lactobacillus and lower levels of Enterobacteriaceae and Clostridia species. Fish oil also reduced neutrophil infiltration as well suggesting that n3 PUFA is anti-inflammatory. In addition, unexpectedly, fish oil supplementation induced oxidative stress in the colon evident by the increased presence of 4-hydroxy-2-nonenal, a lipid peroxide product, and dual oxidase 2, which generates H₂O₂. In addition, catalase, an antioxidant was also low in the fish oil group. Canola oil, which contains n3, n6 PUFAs and a monounsaturated fat oleic acid, alters the microbiota similar to the corn oil group. Overall, our research suggests that n6 PUFA alters the microbial composition, enriching it with detrimental microbes. Fish oil supplementation can reverse this effect. However, we also provide evidence of fish oil supplementation increasing oxidative stress.

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