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Title: Fecal concentrations of bacterially-derived vitamin K forms are associated with gut microbiota composition but not plasma or fecal cytokine concentrations in healthy adults

Author
item KARL, JAMES - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item MEYDANI, MOHSEN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item BARNETT, JUNAIDAH - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item VANEGAS, SALLY - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item BARGER, KATHRYN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item FU XUEYAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item GOLDIN, BARRY - Tufts University
item KANE, ANNE - Tufts University
item RASMUSSEN, HELEN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item VANGAY, PAJAU - University Of Minnesota
item KNIGHTS, DAN - University Of Minnesota
item JONNALAGADDA, SATYA - The Bell Institute
item SALTZMAN, EDWARD - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item ROBERTS, SUSAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item MEYDANI, SIMIN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item BOOTH, SARAH - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/21/2017
Publication Date: 8/16/2017
Citation: Karl, J.P., Meydani, M., Barnett, J.B., Vanegas, S.M., Barger, K., Fu Xueyan, Goldin, B., Kane, A., Rasmussen, H., Vangay, P., Knights, D., Jonnalagadda, S.S., Saltzman, E., Roberts, S.B., Meydani, S.N., Booth, S.L. 2017. Fecal concentrations of bacterially-derived vitamin K forms are associated with gut microbiota composition but not plasma or fecal cytokine concentrations in healthy adults. American Journal of Clinical Nutrition. 106(4):1052-1061. https://doi.org/10.3945/ajcn.117.155424.
DOI: https://doi.org/10.3945/ajcn.117.155424

Interpretive Summary: Bacteria in the gut (known as the gut microbiome) make menaquinones, which are a class of vitamin K compounds that have anti-inflammatory effects. However, it is unclear how the menaquinones made in the gut contribute to vitamin K nutritional status or whether this influences overall inflammation. We examined how two diets - one rich in whole grains and the other rich in refined grains - affect the gut microbiome, vitamin K status, and inflammation in men and postmenopausal women. Over eight weeks, those who consumed the whole-grain rich diet had more menaquinones in their feces compared to those who consumed a refined-grain based diet. The differences in the fecal menaquinones were associated with changes in the types of bacteria in their gut. However, neither the fecal menaquinone concentrations nor the gut bacteria type were associated with inflammation. These findings suggest that dietary changes influence the vitamin K production in the gut, but this does not seem to influence inflammation in generally healthy older adults. Additional research is needed to understand how other health outcomes are related to the forms of vitamin K synthesized by the gut microbiome.

Technical Abstract: Background: Emerging evidence suggests novel roles for bacterially-derived vitamin K forms known as menaquinones (MKn) in health and disease which may be attributable in part to anti-inflammatory effects. However, the relevance of MKn produced by gut bacteria to vitamin K requirements and inflammation is undetermined. Objective: This study aimed to quantify fecal MKn concentrations, and identify associations between fecal MKn concentrations and serum vitamin K concentrations, gut microbiota composition, and inflammation. Design: Fecal and serum MKn concentrations, fecal microbiota composition, and plasma and fecal cytokine concentrations were measured in 80 men and post-menopausal women (48M/32F, 40-65yr) enrolled in a randomized, parallel-arm, provided-food trial. After consuming a run-in diet for 2wk, participants were randomly assigned to consume a whole grain-rich (WG) or refined grain-based (RG) diet for 6wk. Outcomes were measured at weeks 2 and 8. Results: Median total daily excretion of MKn was 850 nmol/d, but highly variable (range: 64-5358 nmol/d). Total fecal concentrations of MKn decreased in WG relative to RG (mean [95% CI]; WG: -8.4 nmol/g [-12.7, -4.2] vs. RG: 3.7 nmol/g [-0.1, 7.6]; P<0.01). However, inter-individual variability in fecal MKn concentrations partitioned individuals into two distinct groups based on inter-individual differences in the concentrations of different MKn forms rather than diet group or time point. The relative abundances of several gut bacteria taxa, Bacteroides and Prevotella in particular, differed between these groups and 42% of identified genera were associated with >/=1 MKn form. MKn were not detected in serum, and neither fecal concentrations of individual MKn nor menaquinone-group was associated with any marker of inflammation. Conclusion: MKn concentrations in the human gut appear highly variable and are associated with gut microbiota composition. However, the health implications remain unclear.