Leone · The Journal of clinical investigation 2026 · randomized crossover trial · n=9

Short-term sleep restriction in humans alters diurnal circulating metabolite profiles, including those of microbial origin.

Cited 2 times in the scientific literature.

Level 2 - randomized trial

Randomized crossover trial in humans

PubMed 41837293 · doi:10.1172/JCI189363 · record verified 2026-08-30

What was done

Nine healthy adults completed a randomized crossover trial with two in-laboratory 24-hour blood sampling protocols (every 120 minutes): one following 3 nights of habitual sleep (8.5 hours/night) and the other following 3 nights of sleep restriction (4.5 hours/night). Meal timing, composition, and caloric intake were held constant. Serum metabolites were profiled via untargeted reverse-phase liquid chromatography-mass spectrometry, and rhythmicity was evaluated with empirical JTK_CYCLE analysis.

What was found

The authors identified 90 metabolites, including 14 microbial or host-microbial co-metabolites. Sleep restriction significantly altered overall serum metabolite composition compared to normal sleep. Several compounds lost diurnal rhythmicity following sleep restriction, including the microbial metabolites butyrate and indole-3-propionic acid. In contrast, new diurnal rhythms emerged in kynurenine (a tryptophan catabolite) and lipid metabolism intermediates. No quantitative concentrations, effect sizes, or exact p-values were reported in the abstract.

Why it matters

This trial demonstrates that short-term sleep restriction directly alters 24-hour rhythms of circulating microbial and host metabolites independently of meal timing and caloric intake. It provides experimental human evidence linking host sleep architecture to circulating gut-microbiome metabolic outputs.

Limits

The sample size was very small (n=9), limiting statistical power and generalizability. The study examined only short-term sleep restriction (3 nights), leaving chronic sleep disruption unassessed. The abstract reports no numerical effect sizes, variance estimates, or exact p-values, and no downstream clinical outcomes were measured.

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