Abstract
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.
Highlights
The effects of nutrition on health are extremely complex
To examine the effects of polyunsaturated fatty acid (PUFA) on the intestinal microbial ecology, we used qPCR and primers specific to the 16S rRNA sequences from clinically important microbes which are altered in inflammatory bowel diseases (IBD) patients or experimental models of intestinal inflammation [4]. v-6 PUFA rich diets enriched the microbiota with Enterobacteriaceae (Figure 1A), which are associated with IBD [18,19,20,21], and Segmented Filamentous Bacteria (SFB; Figure 1A), previously shown to induce responses that drive experimental colitis [22]
While v-6 PUFA rich diets induced the growth of microbes known to induce pro-inflammatory responses, v3 PUFA supplementation reversed this and in parallel enriched beneficial bacteria
Summary
The effects of nutrition on health are extremely complex. In the gastrointestinal (GI) tract, dietary antigens interact with both the microbiota and the host mucosal surface which serves as a gatekeeper to systemic homeostasis. Certain dietary choices alter the ecology of the microbiota (known as dysbiosis; reviewed in [1]), and both dietary lipid intake and the intestinal microbiota have been identified as important factors contributing to the etiology of inflammatory bowel diseases (IBD). Little is known about the effects of dietary lipids on inducing specific microbial changes that are either protective or detrimental in IBD.
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