Urolithin A Ameliorates Athletic Ability and Intestinal Microbiota in Sleep Deprivation from the Perspective of the Gut-Muscle Axis

Abstract

Scope: Urolithin A (UA), a gut-microbiota-derived metabolite of ellagic acid, presents various benefits to intestinal microecology. The presence of "gut-muscle axis" regulating the onset and progression of exercise-related physical frailty and sarcopenia has been recently hypothesized. This study aims to explore the underlying mechanism of gut-muscle axis by which UA enhances muscle strength and fatigue resistance of sleep-deprived (SD) mice.

Methods and results: UA is gavaged to C57BL/6 mice (50 mg kg^-1 bw) before 48-h SD. The results indicate that pretreatment of UA significantly enhances motor ability and energy metabolism. The inflammation is suppressed, and intestinal permeability is improved after prophylactic treatment with UA. The decreased level of serum lipopolysaccharide (LPS) is concomitant with augmentation of the intestinal tight junction proteins. 16s rRNA analysis of colonic contents reveals that UA significantly reduces the abundance of Clostridia_UCG-014 and Candidatus_Saccharimonas, and upregulates Lactobacillus and Muribaculaceae. UA probably influences on gut microbial functions via several energy metabolism pathways, such as carbon metabolism, phosphotransferase system (PTS), and ATP binding cassette (ABC) transporters.

Conclusions: The dietary intervention of UA helps to create a systemic protection, a bidirectional communication connecting the gut microbiota with muscle system, able to alleviate SD-induced mobility impairment and gut dysbiosis.

Keywords: energy metabolism; immunomodulation; intestinal microecology; microbiota‐gut‐muscle axis; urolithin A.