Effect of Heat-Killed Lactiplantibacillus plantarum SNK12 on Sleep Quality and Stress-Related Neuroendocrine and Inflammatory Biomarkers in Adults: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial

Life (Basel). 2025 Dec 24;16(1):26. doi: 10.3390/life16010026.

Abstract

Heat-killed Lactiplantibacillus plantarum SNK12 (SNK), isolated from a traditional Japanese fermented food, has been suggested to influence sleep quality, but human data on sleep improvement with heat-killed lactic acid bacteria (postbiotics) remain limited. We conducted a randomized controlled trial to test whether heat-killed SNK (≥1 × 1011 cells/day for 4 weeks) improves sleep quality and alters stress-related immune and neuroendocrine biomarkers. Healthy adults received SNK or a placebo for 4 weeks. The primary outcome was the Oguri-Shirakawa-Azumi Sleep Inventory MA version (OSA-MA) factor "Sleepiness on Rising"; secondary outcomes were other OSA-MA factors and the stress-related biomarkers salivary cortisol and plasma tumor necrosis factor-α (TNF-α). Compared with placebo, SNK improved Sleepiness on Rising (p = 0.032) and Initiation and Maintenance of Sleep (p = 0.010). Salivary cortisol (p = 0.016) and plasma TNF-α (p = 0.037) were also lower with SNK, and no safety concerns emerged. These concomitant changes in subjective sleep indices and stress-related biomarkers are consistent with modulation of hypothalamic-pituitary-adrenal axis activity and inflammatory pathways along the gut-brain axis. SNK may, therefore, represent a practical postbiotic option to support sleep quality.

Keywords: cortisol; gut–brain axis; heat-killed lactic acid bacteria; hypothalamic–pituitary–adrenal (HPA) axis; postbiotics; randomized controlled trial; sleep quality; tumor necrosis factor-α.