An exploratory case-control study on associations of bacterially derived vitamin K forms with the intestinal microbiome and obesity-related osteoarthritis

Authors: LIU, MINYING - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; MATUSZEK, GREGORY - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; AZACARATE-PERIL, ANDREA - University Of North Carolina; LOESER, RICHARD - University Of North Carolina; SHEA, KYLA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Current Developments in Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/13/2023
Publication Date: 3/16/2023
Citation: Liu, M., Matuszek, G.H., Azacarate-Peril, A., Loeser, R., Shea, K. 2023. An exploratory case-control study on associations of bacterially derived vitamin K forms with the intestinal microbiome and obesity-related osteoarthritis. Current Developments in Nutrition. https://doi.org/10.1016/j.cdnut.2023.100049.
DOI: https://doi.org/10.1016/j.cdnut.2023.100049

Interpretive Summary: Vitamin K has been implicated in osteoarthritis (OA) because certain proteins found in joint tissues require vitamin K to function. Furthermore, prior research indicates metabolites produced by intestinal bacteria are involved in the development and/or progression of OA. One potential class of metabolites are menaquinones, forms of vitamin K produced by bacteria in the intestine. However, it is not known if intestinally-produced menaquinones are relevant to OA. To begin to address this gap, we measured fecal menaquinone concentrations in obese adults with OA and without OA, then determined if the fecal menaquinone profiles differed between the two groups. Although fecal menaquinones were abundant in variable amounts among the participants, the overall fecal menaquinone profiles did not differ with OA status. These findings do not support the idea that intestinally-derived menaquinones are linked to OA.

Technical Abstract: Background: Evidence suggests natural metabolites produced by intestinal microorganisms may have beneficial or harmful effects on osteoarthritis (OA). This could include menaquinones, which are bacterially-synthesized biologically active vitamin K forms abundant in the intestinal microbiome. Objective: The overall goal of this study was to evaluate the association of intestinally-derived menaquinones with obesity-related OA. Methods: This case-control study used data and biospecimens derived from a sub-group of Johnston County Osteoarthritis Study participants. Fecal menaquinone concentrations and microbial composition were determined in 52 obese participants with hand and knee OA and 42 age- and sex-matched obese participants without OA. The inter-relationships between the fecal menaquinones were evaluated using principal component analysis. Differences in alpha and beta diversity and microbial composition across menaquinone clusters were evaluated using analysis of variance. Results: Samples clustered into three groups: cluster 1 characterized by higher fecal menaquinone-9, and -10 concentrations, cluster 2 characterized by lower overall menaquinone concentrations, and cluster 3 characterized by higher menaquinone-12 and -13. Overall, fecal menaquinone clusters did not differ between participants with or without OA (p=0.707). Microbial diversity did not differ across the fecal menaquinone clusters (all F-test p>0.12). However, the relative abundance of bacterial taxa differed among clusters, with a higher abundance of Coprococcus, Prevotella, and Eggerthella in cluster 2 compared to cluster 1, a higher abundance of Oscilospira, Dorea and Eubacterium, and Bacteroides in cluster 3 compared to cluster 1, and a higher abundance of Prevotella, Sutterella and Dorea in cluster 3 compared to cluster 2 (all p<0.001). Conclusion: Menaquinones were variable and abundant in the human gut, but the fecal menaquinone clusters did not differ with OA status. While the relative abundance of specific bacterial taxa differed among fecal menaquinone clusters, the relevance of these differences with respect to vitamin K status and human health is uncertain.