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Title: Exploratory analysis of covariation of microbiota-derived vitamin K and cognition in older adults

Author
item MCCANN, ANGELA - University College Cork
item JEFFERY, IAN - University College Cork
item OULIASS, BOUCHRA - University Of Montreal
item FERLAND, GUYLAINE - University Of Montreal
item FU, XUEYAN - 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
item TRAN, TAM - University College Cork
item O'TOOLE, PAUL - University College Cork
item O'CONNOR, EIBHLIS - University Of Limerick

Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/7/2019
Publication Date: 9/13/2019
Citation: McCann, A., Jeffery, I.B., Ouliass, B., Ferland, G., Fu, X., Booth, S.L., Tran, T.T., O'Toole, P.W., O'Connor, E.M. 2019. Exploratory analysis of covariation of microbiota-derived vitamin K and cognition in older adults. American Journal of Clinical Nutrition. 110(6):1404-1415. https://doi.org/10.1093/ajcn/nqz220.
DOI: https://doi.org/10.1093/ajcn/nqz220

Interpretive Summary: Vitamin K forms have multiple important physiological roles including blood coagulation, beneficial effects on myelin integrity in the brain, and potentially acting as an anti-inflammatory agent. The menaquinone forms of vitamin K appear in much higher concentration in tissues such as the brain than phylloquinone, the main dietary, plant-derived form. Despite knowledge of the importance of vitamin K for brain health, few studies have attempted to measure menaquinone concentrations and biosynthesis by gut commensals and link them to cognition in older adults. The aim of the current study was to investigate the relationship between genes involved in gut-microbiota derived-menaquinone, levels of menaquinone isoforms and cognitive function in older adults. Metagenomic sequencing of the gut microbiome of elderly individuals of different cognitive ability levels was performed. Four menaquinone forms were found to be positively associated with cognitive ability, along with the identification of the key components of the menaquinone biochemical pathway that drive this positive association. This study provides evidence that levels of vitamin K synthesized by the gut microbiome, in particular the longer chain MKs, may have implications for cognitive health in ageing people.

Technical Abstract: Background: Vitamin K has multiple important physiological roles including blood coagulation, beneficial effects on myelin integrity in the brain, and potentially acting as an anti-inflammatory agent. Some intestinal microbes such as members of the genus Bacteroides possess the necessary repertoire of genes to produce vitamin K in the form of menaquinone (MK). MK appears in much higher concentration in tissues, in particular the brain, than phylloquinone (PK) the main dietary, plant-derived form. Lower PK levels have been reported in patients with Alzheimer's Disease while higher serum PK levels have been positively associated with verbal episodic memory in an ageing population. Despite knowledge of the importance of vitamin K for various health parameters, few studies have attempted to measure MK concentration and biosynthesis by gut commensals. Objective: The aim of the current study was to investigate the relationship between genes involved in gut-microbiota derived MK, levels of MK isoforms and cognitive function. Design: Shotgun metagenomic sequencing of the gut microbiome of 74 elderly individuals of different cognitive ability levels was performed. From this, gene counts for microbial MK biosynthesis were determined. Associations between clusters of individuals, grouped based on a similar presence and prevalence of MK biosynthesis genes, and cognitive ability (measured by the Mini Mental State Exam or MMSE) were investigated. Faecal MK concentrations were quantified by HPLC to investigate correlations with subject clusters. Results: Separation of subject groups defined by banded quantification of the genetic potential of their microbiome to biosynthesize MK was associated with significant differences in MMSE scores. Four MK isoforms were found to be positively associated with MMSE, along with the identification of the key components of the MK pathway that drive this positive association. Conclusion: This study provides evidence that levels of vitamin K synthesised by the gut microbiome, in particular the longer chain MKs, may have implications for cognitive health in ageing people.