Bifidobacterium animalis subsp. lactis Bbm-19 ameliorates insomnia by remodeling the gut microbiota and restoring γ-aminobutyric acid and serotonin signaling.

Insomnia induced by 4-chloro-DL-phenylalanine (PCPA) was characterized by shortened sleep duration, prolonged sleep latency, anxiety-like behaviors, and reduced levels of serotonin and gamma-aminobutyric acid (GABA) in the gut, serum, and brain.

• The PCPA mouse model was used to establish insomnia phenotype prior to Bbm-19 intervention.
• Neurochemical deficits were observed across multiple compartments including gut, serum, and brain tissues.
• Behavioral manifestations included both sleep disturbances and anxiety-like behaviors.

Administration of Bbm-19 significantly improved sleep parameters, reduced anxiety-like behaviors, and increased survival in the PCPA-induced insomnia mouse model.

• Bbm-19 was isolated from human breast milk.
• Improvements were observed in sleep duration and sleep latency.
• Survival rates were increased in Bbm-19-treated animals compared to untreated insomnia controls.
• The intervention used integrated behavioral, neurochemical, immunological, and multi-omics approaches to assess outcomes.

Bbm-19 administration restored gut microbiota balance and enriched beneficial taxa including Muribaculaceae bacterium and Stercoribacter sp.

• Metagenomic analysis was used to assess gut microbiota composition.
• Bbm-19 enriched specific beneficial taxa: Muribaculaceae bacterium and Stercoribacter sp.
• Gut microbiota dysregulation was a feature of the PCPA-induced insomnia model that was reversed by Bbm-19.

Bbm-19 reprogrammed microbial metabolic modules, particularly those involved in amino acid metabolism pathways including alanine, aspartate, glutamate, arginine, proline, and tryptophan pathways.

• Metagenomic and metabolomic analyses were integrated to identify metabolic changes.
• Multiple amino acid metabolic pathways were affected, notably tryptophan metabolism (relevant to serotonin synthesis) and glutamate metabolism (relevant to GABA synthesis).
• These metabolic reprogramming effects were attributed to changes in the gut microbiota composition induced by Bbm-19.

Targeted metabolomics confirmed that Bbm-19 increased levels of GABA and serotonin in fecal and brain tissues, along with normalization of inflammatory cytokine profiles.

• GABA and serotonin increases were confirmed in both fecal samples and brain tissues.
• Inflammatory cytokine profiles were normalized following Bbm-19 treatment.
• Targeted metabolomics approach was used to quantify neurotransmitter levels.

Spearman correlation analysis linked Bbm-19-enriched taxa to improved neurotransmitter levels and sleep outcomes.

• Spearman correlation was used to establish associations between specific microbial taxa enriched by Bbm-19 and neurochemical and behavioral outcomes.
• The analysis connected gut microbiota changes to both neurotransmitter levels (GABA, serotonin) and sleep parameters.
• This analysis supported a mechanistic link between microbiota remodeling and sleep improvement.

Bbm-19 outperformed lorazepam in modulating gut-specific metabolic functions and synergistically enhanced lorazepam's effects when co-administered.

• Lorazepam was used as a positive pharmacological control for comparison.
• Bbm-19 demonstrated superior performance to lorazepam specifically in gut metabolic modulation.
• Co-administration of Bbm-19 and lorazepam produced synergistic effects on sleep outcomes.
• This suggests potential clinical utility of combining Bbm-19 with standard pharmacotherapy for insomnia.