The Polyunsaturated Fatty Acids Eicosapentaenoic Acid and Docosahexaenoic Acid, and Vitamin K₁ Modulate the Gut Microbiome: A Study Using an In Vitro Shime Model

Omega-3 polyunsaturated fatty acids (PUFAs) and vitamins exert multiple beneficial effects on host health, some of which may be mediated through the gut microbiome. We investigated the prebiotic potential of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and lipid-soluble phylloquinone (vitamin K-1), each at 0.2x, 1x and 5x using the simulator of the human intestinal microbial ecosystem (SHIME (R)) to exclude in vivo systemic effects and host-microbe interactions.Microbial community composition and, diversity [shotgun metagenomic sequencing] and microbial activity [pH, gas pressure, and production of short-chain fatty acids (SCFAs)] were measured over a period of 48 h. Fermentations supernatants were used to investigate the effect on gut barrier integrity using a Caco-2/goblet cell co-culture model.We found that EPA, DHA and vitamin K-1 increased alpha-diversity at 24 h when compared with control. Moreover, there was an effect on beta-diversity with changes in gut microbial composition, such as an increase in the Firmicutes/Bacteroidetes (F/B) ratio and a consistent increase in Veillonella and Dialister abundances with all treatments. DHA, EPA, and vitamin K-1 also modulated metabolic activity of the gut microbiome by increasing total SCFAs which was related mainly to an increase in propionate (highest with EPA and vitamin K-1 at 0.2x). Finally, we found that EPA and DHA increased gut barrier integrity with DHA at 1x and EPA at 5x (p < 0.05, respectively). In conclusion, our in vitro data further establish a role of PUFAs and vitamin K to modulate the gut microbiome with effects on the production of SCFAs and barrier integrity.