Gut to Brain: Study Reveals Bacterial Molecules Directly Regulate Sleep Cycles

Breakthrough Study Reveals How Gut Bacteria Directly Influence Sleep via Brain Molecules

SEPTEMBER 26, 2025 – In a finding that reshapes our understanding of sleep, scientists at Washington State University (WSU) have discovered direct evidence that molecules from gut bacteria are present in the brain and play a key role in regulating sleep cycles. The research, led by PhD candidate Erika English, identifies a bacterial cell wall component called peptidoglycan (PG) as a central player, challenging the long-held, brain-centric view of sleep control.

From the Gut to the Brain: The Sleep Molecule Connection

The study demonstrated that PG naturally travels to the brain and its levels fluctuate in sync with sleep and wakefulness. This was previously unknown, as PG was only thought to affect sleep when introduced artificially.

"This added a new dimension to what we already know," English stated. "We found PG and its signaling receptors in various brain regions, and their levels change with the time of day and sleep deprivation."

The "Holobiont" Hypothesis: Rethinking Sleep as a Collaboration

This discovery supports a revolutionary theory developed at WSU called the "holobiont" hypothesis of sleep. A holobiont refers to a host (like a human) and all its resident microbes acting as a single unit. This theory proposes that sleep is not solely commanded by the brain but emerges from a continuous dialogue between the body's nervous system and the vast community of microbes in the gut.

"It's not one or the other, it's both. They have to work together," English explained. "Sleep is a process that comes about because of extensive coordination between different systems in the body, including our microbiome."

Evolutionary Roots and Future Treatments

The implications are profound, suggesting that the roots of sleep may extend back billions of years to the activity cycles of bacteria.

"Those microbes have a much longer evolutionary history... We think sleep evolution began eons ago with the activity/inactivity cycle of bacteria," said co-author Professor James Krueger, a renowned sleep researcher.

This paradigm shift opens exciting new avenues for treating sleep disorders. Instead of focusing exclusively on the brain, future therapies could target the gut microbiome or its signaling molecules to promote natural, healthy sleep.

"The world has come to appreciate how important microbes are for health," English added. "It's a very exciting time to expand our understanding of this communication with our microbes."