Clinically, excessive ω-6
polyunsaturated fatty acid (PUFA) and inadequate ω-3 PUFA have been associated with enhanced risks for developing
ulcerative colitis. In rodent models, ω-3 PUFAs have been shown to either attenuate or exacerbate
colitis in different studies. We hypothesized that a high ω-6: ω-3 PUFA ratio would increase
colitis susceptibility through the microbe-immunity
nexus. To address this, we fed post-weaned mice diets rich in ω-6 PUFA (
corn oil) and diets supplemented with ω-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 ω-6 PUFA enriched the microbiota with Enterobacteriaceae, Segmented Filamentous Bacteria and Clostridia spp., all known to induce
inflammation. During
infection-induced
colitis, ω-6 PUFA fed mice had exacerbated intestinal damage, immune cell infiltration,
prostaglandin E2 expression and C. rodentium translocation across the intestinal mucosae. Addition of ω-3 PUFA on a high ω-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, ω-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-α. 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, ω-6 PUFA enriches pro-inflammatory microbes and augments
colitis; but prevents
infection-induced systemic
inflammation. In contrast, ω-3 PUFA supplementation reverses the effects of the ω-6 PUFA diet but impairs
infection-induced responses resulting in
sepsis. We conclude that as an
anti-inflammatory agent, ω-3 PUFA supplementation during
infection may prove detrimental when host inflammatory responses are critical for survival.