Extensive work shows that the human gut microbiome is involved in mental health through bidirectional interactions within the gut-brain axis, which includes the immune, nervous, hormonal and metabolic pathways between the gut and the brain. Therefore, oral ingestion of probiotics can have therapeutic effects on psychiatric symptoms by promoting a healthy and balanced gut microbiome.
In recent years, the literature has accumulated that probiotics made from certain strains of the genera Lactobacillus and Bifidobacterium have the potential to prevent and treat various psychiatric conditions such as depression and anxiety. However, the researchers behind the current study believe that few RCTs have studied the effects of probiotics containing strains of Lactobacillus and Bifidobacterium on the mental health of healthy individuals for analyzes to confirm restoration of the gut microbiome homeostasis – one of the most reliable markers for probiotic effects.
The probiotic NVP-1704 is a mixture of Lactobacillus reuteri NK33 and Bifidobacterium jugendlichis NK98. Several preclinical studies have shown that NVP-1704 can relieve anxiety and depression in mice by modulating the immune response of the gut and the composition of gut microbiota.
The present study aimed to evaluate the efficacy and safety of administering NVP-1704 to treat stress-related symptoms such as depression, anxiety, and insomnia in healthy adults. The research team conducted a randomized, double-blind, placebo-controlled, parallel study at the Seoul National University Bundang Hospital in Korea with a sample size of 22 participants and included an intestinal microbiome analysis to confirm the effect of our intervention.
Participants were randomly assigned to either the intervention or placebo group. They were instructed to take two capsules with water once a day for eight weeks. Each 500 mg capsule of NVP-1704 contained 2.5 x 109 colony forming units of microorganisms (2.0 x 109 CFU for Lactobacillus reuteri NK33 and 0.5 x 109 CFU for Bifidobacterium juvenlichis NK98).
All participants were asked to complete self-assessment questionnaires on symptoms of stress, depression, and anxiety on their first, third, and final visits.
The subjective sleep quality and the symptoms of insomnia were assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI), respectively.
Blood samples were taken during the initial and follow-up examinations. To assess the inflammatory response and hypothalamic-pituitary-adrenal cortex (HPA) activity, we measured serum levels of interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), adrenocorticotropic hormone (ACTH), and cortisol. At the same time, the blood level of the brain-derived neurotrophic factor (BDNF) was evaluated as a neuroplasticity index.
Participants were asked to submit stool samples for bacterial sequencing on the final visit.
24-hour nutritional recalls and food diaries reported on the second, third, and final visits calculated daily intake of calories, carbohydrates, protein, fat, water, fiber, vitamins, and minerals.
The resulting data suggest that NVP-1704 is a safe and well-tolerated probiotic with beneficial effects on depression and sleep in healthy adults. Our study also showed a significant reduction in pro-inflammatory cytokine IL-6 levels in serum after treatment with NVP-1704. Consistent with these results, our microbiome analysis showed that the subjects treated with NVP-1704 had an intestinal microbiota composition with reduced ratios of Enterobacteriaceae to Bifidobacteriaceae and Enterobacteriaceae to Lactobacillaceae, which are associated with better mental health could.
They conclude that the significant reduction in proinflammatory cytokine IL-6 levels in serum suggests that administration of Bifidobacterium and Lactobacillus strains may downregulate proinflammatory cytokine secretion.
According to their report, “Although the exact mechanism needs further elucidation, modulation of neuroinflammatory pathways through beneficial modification of the gut microbiome could be the key components underlying the beneficial effects of NVP-1704. Neuroinflammation, which is triggered by various diseases, plays an important role in the pathophysiology of depression, anxiety and insomnia. Therefore, the suppression of IL-6 could be responsible for the psychotropic effects of treatment with NVP-1704. “
In the future, large-scale, strictly controlled longitudinal studies in humans could be conducted to confirm the positive effects of various probiotics on mental health and sleep.
Lee, HJ; Hong, JK; Kim, J.-K .; Kim, D.-H .; Jang, SW; Han, S.-W .; Yoon, I.-Y.
“Effects of Probiotic NVP-1704 on Mental Health and Sleep in Healthy Adults: An 8-Week Randomized, Double-Blind, Placebo-Controlled Study”
https://doi.org/10.3390/nu13082660 (register DOI)