Mechanism of intestinal stem cell dysfunction from sleep deprivation

Chronic gastrointestinal diseases is one of the features of sleep disturbances but the neural signaling involved in the transmission to the gut is not well understood.

The authors show that sleep deprivation leads to intestinal stem cell (ISC) dysfunction with shortening of crypt-villus architecture and Paneth cell loss.

The researchers uncover a sleep disturbance-responsive neuroendocrine pathway involving dorsal motor nucleus of vagus (DMV), which when hyperactivated, releases acetylcholine from the vagus nerve into the gut.

Acetylcholine triggers 5-hydroxytryptamine (5-HT) release by enterochromaffin cells and suppresses its reuptake via muscarinic receptors, thereby causing a spike in 5-HT levels. Elevated 5-HT induces excessive oxidative stress in ISCs through its receptor HTR4, promoting gut pathologies.

Targeting the dorsal motor nucleus of vagus-vagus nerve-5-HT axis offers therapeutic opportunities for sleep disturbance-associated gastrointestinal disorders.

https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(26)00025-1

https://sciencemission.com/Sleep-disturbance-triggers-aberrant-activation-of-vagus