Lactobacillus brevis M2-Fermented Whey Protein Hydrolysate Increases Slow-Wave Sleep via GABAA Receptors in Rodent Models

• Published in: Foods 2024-06, Vol.13 (13), p.2049
• Main Authors: Lee, Hyowon, Kim, Hyeongyeong, Chang, Yeok Boo, Han, Kisoo, Choi, Hyeon-Son, Han, Sung Hee, Suh, Hyung Joo
• Format: Article
• Language: English
• Subjects: Amino acids; Animal models; Animals; Benzodiazepines; Binding sites; Caffeine; Drug dosages; Electroencephalography; Fermentation; Fermented food; Food; Functional foods & nutraceuticals; GABA; Gene expression; Glucose; Hydrolysates; Insomnia; Lactobacillus brevis; mRNA; NREM sleep; Peptides; Phenols; Proteins; Receptors; REM sleep; Rodents; Sleep; Sleep disorders; Sulfuric acid; Whey; Whey protein; whey protein hydrolysate; γ-Aminobutyric acid A receptors
• ISSN: 2304-8158; 2304-8158
• DOI: 10.3390/foods13132049

In this study, we investigated the effects of whey protein hydrolysate (WPH) fermented with Lactobacillus brevis on sleep behavior and GABAergic mechanisms in rodent models. Fermentation converted the glutamate in WPH to high (3.15 ± 0.21 mg/mL) levels of γ-aminobutyric acid (GABA). Fermented WPH (WP-SF) enhanced sleep duration in mice by increasing GABA content in the brain. The increase in sleep duration induced by WP-SF resulted from an increase in delta wave activity during non-rapid eye movement sleep, and its sleep-promoting effect in a caffeine-induced insomnia model was characterized by an increase in delta waves. WP-SF increased GABAergic receptors at both mRNA and protein levels. Cotreatment with GABAA receptor antagonists abolished the sleep-promoting effects of WP-SF, indicating that WP-SF shares binding sites with antagonists on GABAA receptors. Collectively, WP-SF effectively increased sleep duration by enhancing delta wave activity through GABAergic activation; thus, it is suggested as a functional food-grade ingredient for promoting sleep.