Dietary vitamin K is remodeled by gut microbiota and influences community composition

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 <i>p</i> < .007). Parallel trends were seen in male mice, but were not statistically significant (all <i>p</i> > .05 but <0.1). Next, stable isotope-labeled vitamin K quinones were supplemented to male and female C57BL6 mice (²H₇PK, ¹³C₁₁MK4, ²H₇MK7, ²H₇MK9) and to an <i>in vitro</i> fermentation model inoculated with human stool (²H₇PK, ²H₇MK4, ²H₇MK9, or vitamin K precursor ²H₈-menadione). Vitamin K quinones in feces and culture aliquots were measured using LC-MS. <i>In vivo</i>, supplemented vitamin K quinones were remodeled to other MKn (²H₇- or ¹³C₆-labeled MK4, MK10, MK11, and MK12), but <i>in vitro</i> only the precursor ²H₈-menadione was remodeled to ²H₇MK4, ²H₇MK9, ²H₇MK10, and ²H₇MK11. 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 <i>in vivo</i>.