Targeting the microbiota-gut-brain axis in post-stroke insomnia: a phase-dependent therapeutic framework

Area of Science:

• Neuroscience
• Microbiology
• Immunology

Background:

• Post-stroke insomnia (PSI) affects over half of stroke survivors, hindering neurorehabilitation.
• Traditional sedatives present a dilemma between sleep efficacy and cognitive side effects.
• The microbiota-gut-brain (MGB) axis is an emerging target for treating PSI.

Purpose of the Study:

• To propose a phase-dependent therapeutic framework targeting the MGB axis for post-stroke insomnia.
• To address the cycle of neuroinflammation and hyperarousal following stroke.
• To explore novel interventions beyond traditional sedatives.

Main Methods:

• Investigating the role of gut barrier dysfunction, lipopolysaccharide (LPS) translocation, and NLRP3 inflammasome activation in PSI.
• Analyzing the impact of central tryptophan metabolism via indoleamine 2,3-dioxygenase (IDO) on sleep.
• Proposing phase-dependent interventions: postbiotics in the acute phase and microbiota transplantation/psychobiotics in the chronic phase.

Main Results:

• Acute stroke induces gut barrier collapse, leading to systemic inflammation and tryptophan metabolism disruption.
• This metabolic shift diverts serotonin precursors to neurotoxic kynurenine pathways, causing cortical hyperarousal.
• Sleep fragmentation impairs glymphatic clearance, exacerbating neuroinflammation and creating a vicious cycle.

Conclusions:

• Targeting the MGB axis offers a mechanism-based approach to PSI.
• Acute phase interventions should focus on gut barrier protection (postbiotics) to counter CNS injury-induced immunodepression (CIDS).
• Chronic phase therapy should involve metabolic restoration using live therapeutics (WMT, psychobiotics like Akkermansia muciniphila) for neuroplasticity and recovery.