Details

Autor(en) / Beteiligte

• Karl, J Philip

Titel

Vitamin K biosynthesis and the human gut microbiota

Ort / Verlag

ProQuest Dissertations & Theses

Erscheinungsjahr

2015

Quelle

ProQuest Dissertations & Theses A&I

Beschreibungen/Notizen

• Emerging evidence suggests novel physiologic functions for vitamin K beyond the vitamin's canonical role in hemostasis. Mechanisms underlying these functions are not well characterized, though several are thought to be independent of vitamin K-dependent protein activity and unique to bacterially-synthesized forms of vitamin K known as menaquinones (MKn). Many gut bacteria synthesize MKn, making the human gut a potential source of vitamin K, and factors influencing gut bacteria community composition possible mediators of vitamin K nutriture. However, the contribution of bacterially-synthesized MKn to human vitamin K nutriture is uncertain due, in part, to an incomplete characterization of gut MKn content and of the gut bacteria that synthesize MKn. Moreover, the dietary and non-dietary factors influencing gut bacteria MKn production have not been elucidated. The objective of this research was to leverage recent technological advancements in microbial ecology, bioinformatics and analytical chemistry to characterize gut MKn content, identify associated gut bacteria, and examine effects of diet-mediated changes in gut bacteria community composition on gut MKn content. To meet this objective, a sensitive, selective and high-throughput liquid chromatography-mass spectrometry method for quantifying vitamin K in feces, food and serum was developed and validated. This assay was then utilized to measure fecal vitamin K content in individuals participating in two separate diet interventions investigating the effects of whole grain-based diets on gut bacteria community composition and cardiometabolic health. Collectively, the findings demonstrate that fecal MKn concentrations would exceed the dietary vitamin K requirement if fully absorbed, and are characterized by substantial inter-individual variability in both the quantity and forms of MKn present. Further, gut bacteria community composition appears to explain this variability, and diet modifications that alter gut bacteria community composition measurably impact fecal MKn content. MKn were not detectable in circulation, challenging recent, controversial reports that MKn synthesized by gut bacteria are present in circulation at concentrations within the detectable limits of current assays. Cross-sectional associations between fecal vitamin K content and several biomarkers of cardiometabolic health were observed, and are hypothesis-generating. However, the associations are limited by small sample sizes and were not confirmed in longitudinal analysis. As such, the relevance of these findings to human health is unclear, but merits further investigation. The analytic tools developed and gut bacteria-MKn interrelationships demonstrated as part of this research provide a foundation for those investigations .