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News|Articles|March 25, 2026

RPLC-MS Profiling Reveals How Sleep Loss Disrupts Circulating Microbial Metabolites

Author(s)John Chasse

Researchers utilized untargeted reverse-phase liquid chromatography-mass spectrometry (RPLC-MS) to analyze serum metabolite profiles under normal and sleep-restricted conditions. The RPLC-MS analysis successfully identified 90 circulating metabolites—including 14 of microbial origin—and demonstrated that sleep deprivation significantly disrupts the natural rhythmic cycles of these host and microbial compounds. These findings indicate that microbial metabolites detected via RPLC-MS could potentially serve as clinical biomarkers for the various health and metabolic risks associated with sleep loss.

Gut microbes and their metabolites contribute to the host circulating metabolome and exhibit daytime variation influenced by sleep-wake cycles and meal timing. While sleep deprivation alters the rhythmic circulating metabolome, its impact on microbial metabolites remains unclear. This uncertainty inspired a team of researchers to test whether 24-hour circulating metabolite profiles, including those of microbial origin, differ under normal (habitual) versus short-term restricted sleep. Serum metabolites were characterized using untargeted reverse-phase liquid chromatography-mass spectrometry (RPLC-MS). A paper based on this research was published in The Journal of Clinical Investigation.1

Biological rhythms, whether internally or externally driven, are important for the maintenance of an individual’s health.2 Changes in our modern lifestyle, such as an increased exposure to light at night, the mistiming of light versus dark cues, and patterns of food consumption have all contributed to disruptions or shifts in biological rhythms, which have provoked a profound negative impact on metabolic health.3-5 A key biological rhythm preserved across invertebrates and vertebrates alike, the sleep-wake cycle plays an important role in regulating countless processes that contribute to physiological, emotional, and mental health.6,7

In a randomized crossover design, the researchers had 9 healthy adults complete 2 in-lab 24-hour blood sampling sessions (q120): one following 3 nights of normal sleep (8.5 hours/night), the other following 3 nights of sleep restriction (4.5 hours/night). Meal timing and caloric intake were held constant. Using RPLC-MS, the team was able to identify 90 metabolites, including 14 of microbial origin or derived from host metabolism of microbial products, such as butyrate and tryptophan derivatives. Sleep restriction significantly altered serum metabolite composition compared with normal sleep. While many compounds maintained rhythmicity across conditions, sleep restriction disrupted rhythms of several key compounds, including microbe-derived metabolites. Notably, butyrate and indole-3-propionic acid lost rhythmicity, whereas new rhythms emerged in the tryptophan catabolite, kynurenine, and lipid metabolism intermediates.1

“We provide evidence, write the authors of the study,1 “that microbial metabolites are detectable in human blood and exhibit sleep-dependent rhythmicity. Sleep restriction alters diurnal circulating microbial and host-derived metabolite rhythms even under constant meal timing, composition, and calories. These findings support links between host sleep patterns and gut microbial metabolism and suggest microbial metabolites as potential biomarkers or mediators of sleep loss-associated health risks.”

The research team believes that, with additional study, these rhythmic host- and microbially derived circulating metabolites might form the basis for clinically relevant diagnostic and prognostic biomarkers of sleep-related health and metabolic risks, including cardiometabolic disease, inflammation, and mental health disorders.1

References

  1. Leone, V. A.; Frazier, K.; Kaur, M. et al. Short-Term Sleep Restriction in Humans Alters Diurnal Circulating Metabolite Profiles, Including Those of Microbial Origin. J Clin Invest. 2026, 136 (6), e189363. DOI: 10.1172/JCI189363
  2. Foster, R. G.; Roenneberg, T. Human Responses to the Geophysical Daily, Annual and Lunar cycles. Curr Biol. 2008, 18 (17), R784-R794. DOI: 10.1016/j.cub.2008.07.003
  3. Schwartz, W. J.; Klerman, E. B. Circadian Neurobiology and the Physiologic Regulation of Sleep and Wakefulness. Neurol Clin. 2019, 37 (3), 475-486. DOI: 10.1016/j.ncl.2019.03.001
  4. Hatori, M.; Gronfier, C.; Van Gelder, R. N. et al. Global Rise of Potential Health Hazards Caused by Blue Light-Induced Circadian Disruption in Modern Aging Societies. NPJ Aging Mech Dis. 2017, 3, 9. DOI: 10.1038/s41514-017-0010-2
    Lee, E.; Kim, M. Light and Life at Night as Circadian Rhythm disruptors. Chronobiol Med. 2019, 1 (3), 95-102. DOI: 10.3934/Neuroscience.2016.1.67
  5. Zielinski, M. R.; McKenna, J. T.; McCarley, R. W. Functions and Mechanisms of Sleep. AIMS Neurosci. 2016, 3 (1), 67-104. DOI: 10.3934/Neuroscience.2016.1.67
  6. Perry, G. S.; Patil, S. P.; Presley-Cantrell, L. R. Raising Awareness of Sleep as a Healthy Behavior. Prev Chronic Dis. 2013, 10, E133. DOI: 10.5888/pcd10.130081

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