A growing body of research shows that sleep health is far more complex than a single hormone. Sleep is not governed solely by the brain, but by a quiet highway of signals running between the gastrointestinal tract and the central nervous system. This bidirectional highway is the gut–brain axis. This communication network links neural, endocrine, immune, and microbial pathways that collectively shape stress physiology, autonomic balance, and, ultimately, sleep quality. 

Historically, sleep science has been centered around melatonin, gamma-aminobutyric acid (GABA), and cortical activity. But emerging evidence reveals that signals originating in the gut can meaningfully influence sleep architecture, especially in individuals whose sleep difficulties stem from stress, elevated sympathetic activity, or autonomic dysregulation. 

One of the most intriguing protagonists to emerge is Lactobacillus gasseri CP2305, a postbiotic and gram-positive, non-spore-forming lactic acid bacterium with documented effects on autonomic nervous system regulation and improved sleep quality.

Sleep-Specific Communication Between the Brain and Gut

To understand why a microbe might matter to sleep, it helps to picture how the gut and brain stay in conversation. At the center of this communication network is the vagus nerve, the primary neural highway connecting the gut to the brain. Signals traveling along this pathway continuously inform the central nervous system about the state of the gut environment. High vagal activity corresponds to strong parasympathetic tone, which supports physiological states essential for initiating and maintaining restorative sleep. In times of chronic stress, this dialogue grows tense and sympathetic “fight-or-flight” signaling crowds out the restorative parasympathetic tone. The result is a body that’s poised for action when it should be preparing for rest. Sleep becomes the casualty.

Lactobacillus gasseri CP2305 has been clinically observed to help normalize stress-related sleep disruptions by modulating both autonomic nervous system activity and HPA axis signaling along the gut–brain axis.

Lactobacillus gasseri CP2305 and Sleep Support

Lactobacillus gasseri CP2305, originally classified as a probiotic, is primarily studied in its heat-treated, nonviable form, functioning more as a paraprobiotic. This distinction is important. Unlike probiotics, postbiotics do not require survival through the digestive tract or colonization of the gut. Instead, their benefits stem from bioactive cellular components and metabolites that interact with intestinal and neural pathways. This is meaningful for sleep because stress-related sleep disturbance is an upstream, signaling-driven problem, not a colonization problem. This mechanism is particularly relevant as CP2305’s bioactivity maps directly onto the pathways dysregulated by chronic stress.

In an acute stress setting, including medical students during a cadaver dissection course, a randomized, doubleblind, placebo-controlled study showed that daily CP2305 significantly improved global sleep quality (PSQI; P = 0.038), shortened sleep latency (P = 0.035), and increased sleep duration (P = 0.048) versus placebo. Autonomic markers also shifted in a direction consistent with enhanced parasympathetic tone, aligning physiology with sleep initiation and continuity.

In one of the strongest trials, 69 medical students preparing for their national licensure exam consumed heat-treated CP2305 for 12 weeks. Compared with the placebo group, the CP2305 group showed a better global PSQI (P = 0.0281), shorter sleep latency (EEG; P < 0.001), and a higher percentage of non-REM sleep (P < 0.001). CP2305 also prevented exam-related rises in basal salivary cortisol and supported parasympathetic activity, a physiologic signature favorable for restorative sleep.

Extending to longer-term use, a 24week randomized, doubleblind, placebo-controlled study in 60 adults under chronic stress found that CP2305 reduced anxiety and sleep disturbance, shortened sleep latency, and reduced wake after sleep onset (WASO) on EEG, while increasing deltapower ratio in the first sleep cycle, a marker of deeper, more restorative slow-wave sleep. CP2305 also lowered salivary chromogranin A, indicating reduced sympathetic–adrenomedullary activation, and stabilized stress-related microbiome shifts by attenuating the decline of Bifidobacterium spp. and the rise of Streptococcus spp. under stress.

Conclusion

The connection between the gut–brain axis and sleep has never been clearer. Chronic stress disrupts this pathway, driving autonomic imbalance and changes in gut-derived signaling that collectively undermine sleep quality. Across multiple controlled trials, Lactobacillus gasseri CP2305 has demonstrated the ability to help restore this balance, supporting healthier stress responses, stabilizing autonomic tone, improving gut–brain communication, and ultimately enhancing both subjective and objective measures of sleep. For individuals whose sleep is most vulnerable to stress, CP2305 represents a reliable, upstream approach to promoting more restorative rest.

Learn more about the gut-brain axis: 

Top Tips for Stimulating the Vagus Nerve and Supporting the Gut-Brain Axis

Recent Randomized Controlled Trial Explores Link Between the Gut-Brain Axis and Depression

Supportive Role Probiotics Play on Gut-Brain Axis and Mood Health, According to Recent Review

By Ally LaGrutta, MS, CNS, CSCS