Summary: Researchers at Washington State University found that bacterial cell-wall molecules called peptidoglycan (PG) are present in mouse brains and vary with the sleep–wake cycle. These results support a model in which sleep emerges from dynamic interactions between the brain and the body’s microbiome rather than from brain activity alone.
The study introduces and reinforces a “holobiont condition” view of sleep: sleep regulation as a joint process between host neural systems and resident microbes. The work reframes aspects of sleep science and links microbial signaling to cognition, behavior, and the evolutionary origins of sleep.
Key Facts
- Peptidoglycan detected in brain: Bacterial cell wall molecules were measured in multiple mouse brain regions and showed time-of-day and sleep-related fluctuations.
- Holobiont hypothesis: Sleep may arise from coordinated interactions between the nervous system and the microbiome rather than from brain processes alone.
- Evolutionary and behavioral implications: Findings suggest microbes could have influenced the evolution of sleep and continue to affect cognition and behavior.
Source: Washington State University
New perspective on what causes sleep
Recent research from Washington State University provides evidence that peptidoglycan, a structural component of bacterial cell walls, is naturally present in the brains of mice and that its concentrations change with circadian timing and after sleep deprivation. Because peptidoglycan and related signaling pathways can influence sleep when administered experimentally, the finding that these molecules occur and fluctuate in the brain under normal conditions supports a broader, body–microbe interaction model of sleep regulation.
Erika English, a PhD candidate at WSU and lead author on the published studies, reports that peptidoglycan and its receptor molecules are present in several brain areas and that their levels vary by brain region, time of day, and prior sleep loss. Longtime WSU sleep researcher and Regents Professor James Krueger co-authored one of the papers.
The findings augment a developing hypothesis from WSU that describes sleep as an emergent property of interacting systems—neural circuits within the host and microbial communities that occupy the gut and other tissues. This “holobiont condition” perspective synthesizes two prevailing views of sleep: the traditional brain-centered regulatory model and the “local sleep” model, in which sleep-like states arise within small cellular networks across tissues and then accumulate to produce whole-organism sleep.
According to the proposed model, sleep occurs because multiple levels of biological organization—cells, tissues, organs, neural networks, and microbial populations—coordinate activity over time. “It’s not one or the other, it’s both,” English says. “Sleep really is a process. It happens at many different speeds for different levels of cellular and tissue organization and it comes about because of extensive coordination.”
The study’s measurements revealed region-specific PG levels: the brainstem had comparatively high PG concentrations, while olfactory bulb, hypothalamus, and cortex exhibited lower baseline levels. PG levels reached their lowest point near the transition from rest to active periods and shifted differently across regions after short periods of sleep disruption. RNA-sequencing of somatosensory cortex tissue also identified sleep-loss-related changes in genes associated with peptidoglycan binding and signaling, including Pglyrp1 and Nfil3.
These results tie into broader evidence linking the microbiome to behavior and neural function. Sleep patterns influence gut microbial communities, bacterial infections can alter sleep drive, and microbial metabolites affect host physiology. The WSU team argues that microbes, which have existed far longer than animals, likely influenced the early evolution of activity–inactivity cycles and that molecular signals produced by microbes contributed to primitive sleep-like states that later became integrated with host neural mechanisms.
English notes that growing recognition of the microbiome’s importance for health creates new opportunities to study two-way communication between hosts and their microbes and to explore how microbial signals contribute to behavior and neurological states. The work could inform future approaches to sleep disorders that consider both neural and microbial contributions.
About this sleep and neuroscience research news
Author: Shawn Vestal
Source: Washington State University
Contact: Shawn Vestal – Washington State University
Image credit: Neuroscience News
Original Research (open access): “Bacterial peptidoglycan levels have brain area, time of day, and sleep loss-induced fluctuations” by Erika English et al., Frontiers in Neuroscience.
Abstract
Bacterial peptidoglycan levels have brain area, time of day, and sleep loss-induced fluctuations
Earlier work identified sleep-promoting bacterial cell wall components, including peptidoglycan (PG) and muropeptides, in brain and urine samples from sleep-deprived animals. Host detection of PG triggers downstream signaling that releases effector molecules, such as cytokines implicated in sleep regulation. Accurate physiological measurement of brain PG has been challenging historically.
This study quantified PG in multiple murine brain regions across rest–wake cycles and after controlled sleep disruption. Significant time-of-day variations were present in all regions studied, with lowest PG levels occurring around the rest-to-wake transition (zeitgeber time 12, ZT12). Brainstem PG levels were highest overall, while olfactory bulb, hypothalamus, and cortex showed lower baseline levels. After three hours of sleep disruption, PG increased in somatosensory cortex but decreased in brainstem and hypothalamus; after six hours, PG rose in brainstem and olfactory bulb compared to controls. RNA-seq of somatosensory cortex revealed sleep-loss-associated changes in expression of PG-related genes, including Pglyrp1 and Nfil3.
In summary, brain PG concentrations depend on brain area, circadian timing, and recent sleep history, and sleep loss alters expression of genes linked to PG signaling. These data are consistent with the hypothesis that interactions between host and microbial systems participate in murine sleep regulatory mechanisms.