Investigating the importance of queuosine (Q) as a novel micronutrient in human ageing and brain health

Abstract

Queuosine (Q),a micronutrient derived primarily from the gut microbiome and dietary intake, plays a crucial role in RNA modification and cellular function. This thesis explores the human requirement for Q by quantifying its presence in commonly consumed foods, assessing its levels inhuman biological samples, and evaluating the influence of the gut microbiome on its availability. A dual extraction method and an advanced LC-MS/MS analytical technique were developed and validated to accurately detect both free and tRNA-bound Q metabolites across various sample types. Analysis of a wide range of UK-based dietary items revealed that Q is unevenly distributed, with dairy products, particularly fermented varieties like probiotic yoghurt, emerging as the richest sources. High levels of various Q metabolites were also identified in edible mushrooms and certain animal-derived foods. Data from the NIDAS cohort showed a wide range in daily Q intake among UK adults, influenced by dietary diversity, with a higher intake associated with consumption of multiple Q-rich food sources. A novel SPE and LC-MS/MS method enabled robust extraction and quantification of queuine (q) and Q in human blood. Analysis of blood revealed that q is the predominant circulating form, while Q is present only in trace amounts. Baseline serum q levels correlated with dietary intake, implying the role of diet in q acquisition. Finally, the contribution of the gut microbiota to Q availability was explored through a piglet study, demonstrating that microbial composition, dietary transitions, and zinc supplementation influenced Q metabolite levels. These findings underscore the complex interplay between diet, host metabolism, and the microbiome in regulating Q bioavailability. This research establishes the foundation and advances our understanding of the human requirement for dietary micronutrient Q and its derivatives.

Thesis embargoed until 31st December 2030

Date of Award	Dec 2025
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	CITI-GENS, Horizon 2020
Supervisor	Brian Green (Supervisor) & Jayne Woodside (Supervisor)