Potential impact of urolithin A on pathways relevant to sleep health: a mini review

Sleep is vital to human health, and poor sleep health has been associated with numerous chronic conditions, including cardiovascular disease, obesity, depression, and type 2 diabetes. Recently, an emerging area of research has focused on the relationship between dietary polyphenols and sleep health. This connection may be mediated by the gut microbiota and polyphenol-derived microbial metabolites, which also exert biologically relevant effects. One such metabolite, urolithin A, has been shown to improve mitochondrial function, muscle strength, and inflammation in humans. However, its potential effect on sleep remains unexplored. Thus, this mini review aimed to summarize the current evidence on the effect of urolithin A on sleep-relevant pathways and to explore the possible mechanisms underlying this effect. Although no study directly investigating the effect of urolithin A on sleep outcomes was identified, our search found four preclinical studies that included outcomes relevant to sleep. These studies provide mechanistic plausibility for the relationship between urolithin A and sleep health through direct and indirect mechanisms such as modulation of the central clock, protection against neuroinflammation caused by sleep deprivation, and modulation of the gut microbiota. However, to elucidate the direct effect of urolithin A on sleep, studies with specific sleep measures such as electroencephalogram, actigraphy, and/or polysomnography are still required. Taken together, this represents a novel direction in polyphenol-derived microbial metabolite research with many opportunities for future research.