Abstract
Vitamins have well-established roles in bacterial metabolism. Menaquinones (MKn, n = prenyl units in sidechain) are bacterially produced forms of vitamin K produced by the gut microbiota and consumed in the diet. Little is known about the influence of dietary vitamin K quinones on gut microbial composition and MKn production. Here, male and female C57BL6 mice were fed a vitamin K deficient diet or vitamin K sufficient diets containing phylloquinone (PK, plant-based vitamin K form), MK4, and/or MK9. DNA was extracted from cecal contents and 16S sequencing conducted to assess microbial composition. Cecal microbial community composition was significantly different in vitamin K deficient female mice compared to females on vitamin K sufficient diets (all p < .007). Parallel trends were seen in male mice, but were not statistically significant (all p > .05 but <0.1). Next, stable isotope-labeled vitamin K quinones were supplemented to male and female C57BL6 mice ((2)H(7)PK, (13)C(11)MK4, (2)H(7)MK7, (2)H(7)MK9) and to an in vitro fermentation model inoculated with human stool ((2)H(7)PK, (2)H(7)MK4, (2)H(7)MK9, or vitamin K precursor (2)H(8)-menadione). Vitamin K quinones in feces and culture aliquots were measured using LC-MS. In vivo, supplemented vitamin K quinones were remodeled to other MKn ((2)H(7)- or (13)C(6)-labeled MK4, MK10, MK11, and MK12), but in vitro only the precursor (2)H(8)-menadione was remodeled to (2)H(7)MK4, (2)H(7)MK9, (2)H(7)MK10, and (2)H(7)MK11. These results suggest that dietary vitamin K deficiency alters the gut microbial community composition. Further studies are needed to determine if menadione generated by host metabolism may serve as an intermediate in dietary vitamin K remodeling in vivo.