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

Short-term sleep restriction significantly altered serum metabolite composition compared with normal sleep in healthy adults.

• Randomized crossover design with 9 healthy adults completing two in-lab 24-hour blood sampling sessions
• One condition involved 3 nights of normal sleep (8.5 hours/night) and the other 3 nights of sleep restriction (4.5 hours/night)
• Blood samples were collected every 120 minutes (q120) over 24-hour periods
• Meal timing and caloric intake were held constant across both conditions to isolate sleep effects
• Serum metabolites were characterized using untargeted reverse-phase liquid chromatography-mass spectrometry

A total of 90 metabolites were identified, including 14 of microbial origin or derived from host metabolism of microbial products.

• The 14 microbially-related metabolites included compounds such as butyrate and tryptophan derivatives
• Metabolites included those derived from microbial products processed through host metabolism
• Rhythmicity was assessed using empirical JTK_CYCLE analysis
• The metabolites spanned microbial and host-derived categories

Butyrate and indole-3-propionic acid lost circadian rhythmicity under sleep restriction conditions.

• Both butyrate and indole-3-propionic acid maintained rhythmicity under normal sleep (8.5 hours/night)
• These microbe-derived metabolites lost their diurnal rhythmic patterns following 3 nights of sleep restriction (4.5 hours/night)
• Butyrate is a short-chain fatty acid of microbial origin; indole-3-propionic acid is a tryptophan-derived microbial metabolite
• Loss of rhythmicity occurred despite constant meal timing, composition, and caloric intake

New circadian rhythms emerged in kynurenine and lipid metabolism intermediates under sleep restriction.

• Kynurenine, a tryptophan catabolite, gained rhythmicity under sleep restriction that was not present under normal sleep
• Lipid metabolism intermediates also acquired new rhythmic patterns under sleep restriction
• These emergent rhythms suggest sleep restriction reorganizes the timing of metabolic processes
• The emergence of kynurenine rhythmicity is notable given kynurenine's role in immune and neurological function

Many metabolites maintained rhythmicity across both normal sleep and sleep restriction conditions.

• While sleep restriction disrupted rhythms of several key compounds, a number of compounds maintained rhythmicity across both conditions
• This suggests that sleep restriction selectively disrupts rather than globally abolishing circadian metabolite rhythms
• The selective disruption occurred even under controlled conditions of constant meal timing, composition, and calories

Microbial metabolites detectable in human blood exhibit sleep-dependent rhythmicity, supporting links between host sleep patterns and gut microbial metabolism.

• The study provides evidence that microbially-derived metabolites are detectable in human serum
• These metabolites show diurnal variation that is influenced by sleep conditions
• Sleep restriction altered these rhythms even when meal timing, composition, and caloric intake were held constant
• Authors suggest microbial metabolites may serve as potential biomarkers or mediators of sleep loss-associated health risks