4.6 Article

Fish Oil Attenuates Omega-6 Polyunsaturated Fatty Acid-Induced Dysbiosis and Infectious Colitis but Impairs LPS Dephosphorylation Activity Causing Sepsis

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PLOS ONE
卷 8, 期 2, 页码 -

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PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0055468

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  1. Intestinal Disease Education and Awareness Society
  2. Bill & Melinda Gates Foundation
  3. Crohn's and Colitis Foundation of Canada
  4. Canadian Association of Gastroenterology

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Clinically, excessive omega-6 polyunsaturated fatty acid (PUFA) and inadequate omega-3 PUFA have been associated with enhanced risks for developing ulcerative colitis. In rodent models, omega-3 PUFAs have been shown to either attenuate or exacerbate colitis in different studies. We hypothesized that a high omega-6: omega-3 PUFA ratio would increase colitis susceptibility through the microbe-immunity nexus. To address this, we fed post-weaned mice diets rich in omega-6 PUFA (corn oil) and diets supplemented with omega-3 PUFA (corn oil+fish oil) for 5 weeks. We evaluated the intestinal microbiota, induced colitis with Citrobacter rodentium and followed disease progression. We found that omega-6 PUFA enriched the microbiota with Enterobacteriaceae, Segmented Filamentous Bacteria and Clostridia spp., all known to induce inflammation. During infection-induced colitis, omega-6 PUFA fed mice had exacerbated intestinal damage, immune cell infiltration, prostaglandin E2 expression and C. rodentium translocation across the intestinal mucosae. Addition of omega-3 PUFA on a high omega-6 PUFA diet, reversed inflammatory-inducing microbial blooms and enriched beneficial microbes like Lactobacillus and Bifidobacteria, reduced immune cell infiltration and impaired cytokine/chemokine induction during infection. While, omega-3 PUFA supplementation protected against severe colitis, these mice suffered greater mortality associated with sepsis-related serum factors such as LPS binding protein, IL-15 and TNF-alpha. These mice also demonstrated decreased expression of intestinal alkaline phosphatase and an inability to dephosphorylate LPS. Thus, the colonic microbiota is altered differentially through varying PUFA composition, conferring altered susceptibility to colitis. Overall, omega-6 PUFA enriches pro-inflammatory microbes and augments colitis; but prevents infection-induced systemic inflammation. In contrast, omega-3 PUFA supplementation reverses the effects of the omega-6 PUFA diet but impairs infection-induced responses resulting in sepsis. We conclude that as an anti-inflammatory agent, omega-3 PUFA supplementation during infection may prove detrimental when host inflammatory responses are critical for survival.

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