Mental health disorders are increasingly recognized as a major public health concern worldwide, affecting millions of individuals across diverse demographic groups.
The growing awareness of mental health challenges has led to broader public discussions and a deeper understanding of the profound impact that conditions like depression can have on daily functioning, quality of life, and long-term health.
While major depressive disorder (MDD) remains a primary focus in mental health treatment, many individuals experience depressive symptoms that fall short of the full diagnostic criteria for MDD. This condition, often termed subthreshold depression (sD), encompasses a range of depressive symptoms that are less severe but still pose considerable risks.
Individuals with sD can face significant impairments in work, relationships, and general wellbeing, with an increased risk of progressing to more serious depressive disorders if left untreated.¹ Yet, treatment options for sD are limited, often leaving many individuals without formal treatment interventions.
Emerging research is exploring the potential role of probiotics – live microorganisms that promote a healthy balance of gut bacteria – in managing symptoms of sD. The connection between gut health and brain function, known as the gut-brain axis, suggests that enhancing gut health and modifying gut microbiota might positively influence mood and emotional regulation.
The potential of probiotics as a non-invasive, accessible, and cost-effective intervention for sD warrants further investigation, especially as mental health professionals seek alternative solutions to support individuals who do not qualify for more intensive treatments.
A tailored blend
At Probiotical, enhancing the quality of life for people with sD has been a key focus. To this end, the company developed Bifizen®, a probiotic specifically formulated to address mental well-being in both healthy individuals and those living with psychiatric disorders.
The product is composed of four probiotic strains – Lactiplantibacillus plantarum LP01, Lacticaseibacillus rhamnosus LR06, Limosilactobacillus fermentum LF16, and Bifidobacterium longum 04. Each strain has been specifically selected for its unique mechanism of action aimed at alleviating symptoms of mood disorders.
Research has linked alterations in the human gut microbiota compositions to mood disorders and neuropsychiatric disorders.² This includes a decreased abundance of beneficial bacteria such as Lactobacillus, Faecalibacterium, and Bifidobacterium, alongside an increase in lipopolysaccharides (LPS)-producing bacteria.
These changes are associated with increased gut permeability, systemic inflammation, neuroinflammation, and oxidative and nitrosative stress.³⁻⁶ The strains in Bifizen® have been explored for their collective activity against these factors, demonstrating a synergistic effect of the blend compared to the impact of single strains alone.⁷
The Bifizen® strains were selected for their strong antipathogenic activity against E. coli and K. pneumoniae, with LR06 and LP01 also being active against enterohemorrhagic E. coli.8 Additionally, LP01 is effective against E. faecalis and S. aureus, and LF16 significantly opposes the growth of various Candida spp. strains.⁹
Probiotics: Backed by the science
To assess the benefits of Bifizen® for individuals living with sD, Probiotical conducted a double-blind, randomised, placebo-controlled trial to evaluate the product’s efficacy in reducing depressive symptom severity.¹⁰
Both the probiotic and the placebo were taken daily for 12 weeks, with assessments of psychological symptom severity and biomarkers – including glycaemia, inflammation (high-sensitivity C-reactive protein, (hs-CRP)), antioxidant status (total glutathione (GSH)) and stress (cortisol awakening response, (CAR)) – measured at baseline, 6 and 12 weeks.
The study found that probiotic supplementation significantly reduced depression and anxiety scores at both 6 and 12 weeks, with these improvements persisting in a 6-week post-intervention follow-up.
Biomarker analysis from saliva and blood samples revealed notable physiological improvements in the probiotic group compared to placebo. Specifically, probiotic supplementation was associated with lower CAR, reduced levels of hs-CRP, and increased GSH, indicators linked to inflammation and oxidative stress. These findings support the inflammatory model of depression, which correlates elevated hs-CRP levels with depressive symptoms.
The reduction in CAR aligns with a gradual modification of gut microbiota, potentially impacting stress regulation through the gut-brain axis. The use of salivary cortisol in the study allowed for more sensitive detection of short-term changes. Additionally, increased GSH levels indicate a reduction in oxidative stress, previously linked to mood disorders.
Metabolically, the probiotic group experienced reductions in fasting plasma glucose, with levels normalizing among participants who initially showed elevated glucose levels. This improvement in glycemic control underscores the potential benefit of probiotics for enhancing metabolic health.
While the placebo group also showed some improvements, the specific physiological changes in the probiotic group suggest that these supplements may offer a safe and effective adjunct for managing sD. Given the absence of side effects and ease of implementation, the study supports the use of probiotics as a valuable non-pharmacological tool for mental health support.
The blood and saliva biomarker findings were not subjected to any placebo effect, strengthening the results’ validity. The study authors note that these findings demonstrate a link between biomarkers of inflammation and oxidative stress with depressive symptoms, aligning with previous studies in the area.
Adding to the evidence
The results of the study on participants with sD align with previous research carried out by Probiotical on Bifizen® since 2016. In particular, two further double-blind, placebo-controlled studies on healthy volunteers found that a daily dose of the probiotic for a six-week period was able to significantly improve mood.¹¹⁻¹⁴
These studies also reported other benefits, including a reduction in depressive mood state and anger/hostility, which both persisted three weeks after washout. Additionally, participants experienced improvements in fatigue levels, notable enhancements in sleep quality, better adoption of avoidance strategies, and an increased inclination towards new experiences.
Furthermore, a correlation between changes in gut microbiota composition following the probiotic intake and psychological improvements was found in certain clusters of the study population.
In another study, Bifizen® significantly altered the metabolic profiles in both urine and serum of healthy subjects after eight weeks of treatment, without altering the individual phenotype.¹⁵ These results suggest that Bifizen® influences various metabolic pathways, potentially affecting energy balance, nutrient absorption, and the metabolism of amino acids, fatty acids, and bile acids.
From science-backed R&D to final product
Given these positive outcomes, particularly in mood improvement, it is significant to note that mood disorders are more likely to occur in women.¹⁶ This makes the probiotic an ideal candidate for targeting improvements in women’s health.
For companies looking to incorporate the probiotic into their offerings, it is available ready to market and can also be integrated into broader products specifically designed for women. The product is allergen-free and available in hydrosoluble powder or capsule forms of delivery.
Probiotical is a full-service company that can handle the development of a probiotic all the way from initial R&D to the marketing of the final product. With its scientific backing and targeted formulation, Bifizen® offers a promising, accessible option for supporting mental health and quality of life and stands ready to be integrated into personalised, holistic health solutions for diverse populations.
References
1. Fergusson, D.M.; Subthreshold Depression in Adolescence and Mental Health Outcomes in Adulthood. Arch Gen Psychiatry. 2005;62(1):66–72.
2. Valle, C G-D.; et al. Association between gut microbiota and psychiatric disorders: a systematic review. Front. Psychol., Sec. Health Psychology. 2023; 14.
3. Bharwani, A.; et al. Structural & functional consequences of chronic psychosocial stress on the microbiome & host. Psychoneuroendocrinology. 2016; 63, pp.217-227.
4. Bauer, M.; et al. Inflammation in psychiatric disorders: what comes first?. Annals of the New York Academy of Sciences. 2018; 1437: 1.
5. Maes, M.; et al. In depression, bacterial translocation may drive inflammatory responses, oxidative and nitrosative stress (O&NS), and autoimmune responses directed against O&NS-damaged neoepitopes. Acta Psychiatrica Scandinavica. 2013; 127: 5.
6. Marin, I., et al. Microbiota alteration is associated with the development of stress-induced despair behavior. Sci Rep 7, 2017; 43859.
7. Visciglia, A., et al. Probiotics and Gut-Brain Axis: Insights on local and systemic mechanisms of action. Poster from the 12th Probiotics, Prebiotics & New Foods, Nutraceutical and Botanicals for Nutrition & Human and Microbiota Health, held in Rome on 12-14 September 2021.
8. Mogna, L.; et al. Assessment of the in vitro inhibitory activity of specific probiotic bacteria against different Escherichia coli strains. J Clin Gastroenterol. 2012 Oct;46 Suppl:S29-32.
9. Adu, K. T.; et al. Coronavirus and Probiotics: Past, Present and Future. Journal of Probiotics and Health. 2020; 8,2.
10. Moschonis, G.; et al. Evaluation of a probiotic blend on psychosocial health and biomarkers of inflammatory, immune and stress response in adults with subthreshold depression: a double-blind, randomised, placebo-controlled trial. Cambridge University Press. 2024; 1-15.
11. Marotta, A.; et al. Effects of Probiotics on Cognitive Reactivity, Mood, and Sleep Quality. Front. Psychiatry. Sec. Mood Disorders. 2019.
12. Calgaro, M.; et al. Metabarcoding analysis of gut microbiota of healthy individuals reveals impact of probiotic and maltodextrin consumption. Beneficial Microbes. 2021; 12(2), 121-136.
13. Walden, K. E.; et al. A randomized controlled trial to examine the impact of a multi-strain probiotic on self-reported indicators of depression, anxiety, mood, and associated biomarkers. Front. Nutr. Sec. Nutrition, Psychology and Brain Health. 2023; 10.
14. Kerksick, C.M.; et al. Multi-strain probiotic improves subjective sleep quality with no impact on body composition, hemodynamics, and physical activity. Beneficial Microbes. 2024; 15(2), 179-194.
15. Di Cesare, F.; et al. Exploring the Effects of Probiotic Treatment on Urinary and Serum Metabolic Profiles in Healthy Individuals. Journal of Proteome Research. 2023 22 (12), 3866-3878.
16. Albert, P,R.; et al. Why is depression more prevalent in women? J Psychiatry Neurosci. 2015 Jul;40(4):219-21.
