Stress is an unavoidable part of daily life. It can stem from social, occupational, and environmental pressures. While short-term stress can sharpen focus and enhance performance, prolonged or repeated stress can impair our capacity to cope and contribute to a wide range of adverse health outcomes. Over the past three decades, stress levels in the U.S. have steadily increased, with symptoms presenting both physically and psychologically.
What Happens to the Body Under Chronic Stress?
Chronic stress activates the hypothalamic–pituitary–adrenal (HPA) axis, leading to elevations in cortisol and inflammatory signaling. Sustained HPA axis activation is associated with increased circulating cytokines and altered immune regulation, both implicated in mood disturbances and stress-related conditions.
Over time, persistent stress may disrupt:
Stress and the Gut–Brain Axis
In relation to the gut, chronic stress can alter the composition and stability of our microbiota. Changes in microbial diversity and intestinal permeability may amplify inflammatory signaling and disrupt communication between the gut and the central nervous system. These changes occur within the microbiota–gut–brain axis, the bidirectional communication network linking intestinal microbial communities with brain function.
This is where psychobiotics and para-psychobiotics can come into play. By acting on the gut–brain axis and supporting our microbiome balance, these specific microbial strains may help improve communication between the gut and the brain, contributing to improved stress regulation.
Psychobiotics vs. Para-Psychobiotics
Psychobiotics
Psychobiotics are defined as microorganisms that, when ingested in adequate amounts, confer mental health benefits. They may produce neuroactive compounds such as GABA and serotonin, influencing the brain–gut axis by helping exert anxiolytic or antidepressant effects.
Examples include:
Para-Psychobiotics
Para-psychobiotics are a relatively new term used to describe nonviable, heat-treated microbial cells that confer mental health benefits when consumed in adequate amounts. In the scientific literature, Lactobacillus gasseri CP2305 is recognized as the first strain referred to as a “para-psychobiotic.”
Unlike live probiotics, they:
Lactobacillus gasseri CP2305
Lactobacillus gasseri CP2305 is a lactic acid bacterium isolate derived from the stool of healthy adults. In its heat-treated, nonviable form, CP2305 retains biological activity, despite lacking metabolic function, making it clinically relevant as a para-psychobiotic.
Evidence from Clinical Trials
Multiple randomized controlled trials have evaluated heat-treated Lactobacillus gasseri CP2305 in healthy adults exposed to sustained psychological stress. Study populations included medical and university students during predictable stress periods such as board examinations.
Research has evaluated both:
Rather than preventing stress itself, CP2305 appeared to significantly blunt stress-related outcomes in these populations.
Observed Outcomes Included:
Across validated stress and sleep questionnaires, including the General Health Questionnaire (GHQ-28), the State-Trait Anxiety Inventory (STAI), and the Pittsburgh Sleep Quality Index (PSQI), placebo groups showed worsening psychological distress during high-stress periods, while CP2305 supplementation maintained greater stability.
Mechanisms of CP2305
Psychological stress influences inflammatory signaling, immune activation, and microbial balance. These changes impact central nervous system function through the microbiota–gut–brain axis. CP2305 appears to support stress resilience by interacting with these pathways.
Research suggests it may:
SCFAs, often produced by Lactobacillus species, play important roles in gut barrier integrity and immune regulation. Emerging evidence also suggests CP2305 may influence GABA, the main neurotransmitter involved in calming nervous system activity during periods of persistent stress.
Summary
As prolonged stress continues to impact physical and mental health in today’s world, its effects extend beyond just our mood and are known to impact immune regulation and gastrointestinal health. As understanding of the microbiota–gut–brain axis expands, microbial-based strategies have gained attention for their role in stress regulation.
Clinical research evaluating heat-treated Lactobacillus gasseri CP2305 demonstrates:
As interest in non-viable microbial interventions grows, CP2305 represents a clinically studied example of how a targeted approach to gut–brain pathways may contribute to improved stress resilience.
Learn more about the gut-brain axis:
Top Tips for Stimulating the Vagus Nerve and Supporting the Gut-Brain Axis
Short-Chain Fatty Acids: What Are They and How Do They Support the Gut-Brain Axis?
Recent Randomized Controlled Trial Explores Link Between the Gut-Brain Axis and Depression
By Jesse Martin, MS
Designs for Health has been dedicated to being the most trusted source for superior quality, science-based nutritional products for nearly three decades. We’re committed to maximizing successful health outcomes by providing healthcare practitioners with comprehensive support through our extensive product line, ongoing clinical education, and practice development programs. The blogs we publish here cover a range of topics, including new and original approaches to diet and healthcare, analyses of the latest cutting-edge research, deep-dives into specific nutrients, botanicals, nutraceuticals and more, all fully referenced for those who want to dig deeper into the primary literature.
