Effects of heat-treated Lactobacillus gasseri CP2305 on brain oscillatory activity and mental stress in healthy adults: a double-blind, randomized, crossover, placebo-controlled trial

Background Gut health and brain activity are closely linked, and the gut−brain axis plays a crucial role in regulating mental health. Interventions using beneficial microbes, such as probiotics and postbiotics, are gaining attention as promising approaches to support mental health. This study aimed to evaluate the effects of postbiotic heat-treated Lactobacillus gasseri CP2305 (CP2305) on mental stress and alpha oscillatory activity in the brain. Methods This double-blind, randomized, crossover, placebo-controlled study included 28 healthy participants aged 20–44 years. The participants underwent two trial sessions and consumed a single dose of tablets containing heat-treated CP2305 (postbiotic; 1 × 10 10 cells) or matching placebo tablets. In each session, electroencephalography (EEG) at eight positions was recorded from before to 60 min after ingestion to measure the alpha power. Heart rate variability was also recorded to calculate the root mean square of successive differences (RMSSD), an indicator of parasympathetic activity. The effects on mental state were evaluated using the visual analog scale (VAS) and Profile of Mood States, 2nd edition (POMS2). An in vitro study was conducted using the enterochromaffin cell line RIN14B to measure serotonin (5-HT) secretion levels following the heat-treated CP2305 administration. Results The alpha power showed a significantly greater increase from baseline following consumption of heat-treated CP2305 compared with the placebo. The change in the RMSSD from baseline was significantly greater following consumption of heat-treated CP2305 than following the placebo. Both the mental stress VAS and POMS2 tension–anxiety scores showed significantly greater improvements following consumption of heat-treated CP2305 compared with the placebo. In the in vitro 5-HT assay, extracellular 5-HT levels were significantly higher under the heat-treated CP2305 condition than under the control condition. Conclusion This is the first clinical study to examine the effects of postbiotics on alpha oscillatory activity in the brain. Heat-treated CP2305 consumption was associated with modulation of brain activity, enhancement of parasympathetic activity, and alleviation of stress, indicating its potential as a functional food ingredient for mental health support. These beneficial effects may be partly associated with alterations in gut-derived 5-HT signaling induced by heat-treated CP2305. However, further studies are required to elucidate the underlying mechanisms. Clinical trial registration https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000064175 , Identifier UMIN000056164.