Bifidobacterium longum subsp. longum Reduces Perceived Psychological Stress in Healthy Adults: An Exploratory Clinical Trial.

Nutrients. 2023;15(14)
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Psychosocial stress is a common issue and one way in which nutrition may modulate the stress response is via the microbiota-gut-brain axis. This 6-week randomised, double-blind, placebo-controlled trial of 45 healthy adults with mild-to-moderate stress evaluated the effects of Bifidobacterium longum (BL) NCC3001 on psychological and physiological markers of stress and the response to an acute stress test. Outcome measures included cortisol awakening response, heart rate, heart rate variability and various questionnaires assessing stress, anxiety, depression, sleep and gastrointestinal symptoms. Compared to placebo, probiotic intake led to a significant decrease in perceived stress and an improvement in subjective sleep after 6 weeks. There was no difference in cortisol awakening response. The subjects in both groups did not experience significant gastrointestinal symptoms and scored low on anxiety and depression at baseline. In response to the acute stress test, cortisol levels were higher in the probiotic than the placebo group, whilst no clear differences were seen in heart rate and heart rate variability. Subjects in the probiotic group had a lower pain experience during the stress test whilst subjects in the placebo group had an increase in positive mood following the test. The authors conclude that these results support their hypothesis that BL NCC3001 may alleviate stress and improve sleep in adults with moderate stress levels.

Expert Review

Conflicts of interest: None

Take Home Message:
  • There is mounting evidence to suggest that nutritional interventions can influence our stress responses. One of the routes by which nutrition can influence physiological and psychological stress responses involves the microbiota– gut–brain-axis.
  • This exploratory trial suggests that supplementation with Bifidobacterium longum (BL) strain NCC3001 leads to a beneficial effect on stress relief and improves subjective sleep quality in a healthy adult population reporting moderate levels of psychological stress.

Evidence Category:
  • A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
  • X B: Systematic reviews including RCTs of limited number
  • C: Non-randomized trials, observational studies, narrative reviews
  • D: Case-reports, evidence-based clinical findings
  • E: Opinion piece, other

Summary Review:

A randomised, placebo-controlled, two-arm, parallel, double-blind exploratory clinical trial was conducted to investigate the effect Bifidobacterium longum (BL) strain NCC3001 on stress-related psychological and physiological parameters and acute stress in healthy adults who typically experience mild-to-moderate-levels of stress.


47 Participants between the ages of 25-65 years old with mild-to-moderate psychological stress received 1x1010 CFU of Bifidobacterium longum (BL) strain NCC3001 daily or a placebo for 6 weeks.

Participants completed the Perceived Stress Scale (PSS), the Hospital Anxiety and Depression Scales (HAD-A and HADS-D), the Gastrointestinal Symptom Rating Scale (GSRA), the Pittsburgh Sleep Quality Index (PSQI) questionnaire, the Positive and Negative Affect Schedule (PANAS), the State Trait Anxiety Inventory (STAI-6), the Maastricht Acute Stress Test (MAST) and the Visual Analog Scales (VAS, which measures pain intensity) during the clinical study. The Depression, Anxiety and Stress Scale (DASS-42) questionnaire was also used to depict the progression of the participants through the study.

Faecal samples were taken at baseline and 6 weeks and awakening saliva samples were taken at baseline, 2, 4, 6 and 8 weeks. At the endpoint, 45/49 (91%) of the subjects completed the study. One participant reported an adverse event and the other withdrew without an explanation. Two participants were excluded from the full analysis.


The primary outcomes were:

  • After 6-week of the probiotic intervention, there was a significant decrease in perceived stress in the probiotic group (21.4%) compared to the placebo group (-10.2%), p = 0.017.
  • There was a significant improvement in subjective sleep in the probiotic group compared to the placebo group (p = 0.037).
  • There was a significant decrease in the positive PANAS change score from the pre-stressor stage in the probiotic group compared to the placebo group (p = 0.01).
  • There were lower pain values (VAS) scores from pre-stressor to post-stressor in the probiotic group compared to the placebo group (p = 0.05).
  • There was no significant difference between groups in anxiety (HADS-A) and Depression (HADS_D) scores.


Oral supplementation with BL NCC3001 may have beneficial effects on stress relief and improves subjective sleep quality in a healthy adult population reporting moderate levels of psychological stress.

Clinical practice applications:
  • While the mechanism underlying the correlation between the microbiota and the gut-brain-axis is not fully understood, it is thought to play a critical role in the links between the microbiota, mood, stress, and brain health.
  • This exploratory trial additionally supports the potential of specific probiotics being used to reduce perceived stress and improve subjective sleep quality in healthy adults.

Considerations for future research:
  • Larger, powered clinical trials are needed to provide further insights into the mechanisms underlying the stress-relieving and sleep-improving effect of Bifidobacterium longum.
  • Furthermore, the dosage and duration of the probiotics need further investigation in a larger healthy population.
  • Comparative research is needed to help investigate the effect of different probiotic strains on stress relief and sleep quality.


Emerging science shows that probiotic intake may impact stress and mental health. We investigated the effect of a 6-week intervention with Bifidobacterium longum (BL) NCC3001 (1 × 1010 CFU/daily) on stress-related psychological and physiological parameters in 45 healthy adults with mild-to-moderate stress using a randomized, placebo-controlled, two-arm, parallel, double-blind design. The main results showed that supplementation with the probiotic significantly reduced the perceived stress and improved the subjective sleep quality score compared to placebo. Comparing the two groups, momentary subjective assessments concomitant to the Maastricht Acute Stress Test revealed a lower amount of pain experience in the probiotic group and a higher amount of relief at the end of the procedure in the placebo group, reflected by higher scores in the positive affect state. The awakening of the salivary cortisol response was not affected by the intervention, yet the reduction observed in the salivary cortisol stress response post-intervention was higher in the placebo group than the probiotic group. Multivariate analysis further indicated that a reduction in perceived stress correlated with a reduction in anxiety, in depression, and in the cortisol awakening response after the 6-week intervention. This exploratory trial provides promising insights into BL NCC3001 to reduce perceived stress in a healthy population and supports the potential of nutritional solutions including probiotics to improve mental health.

Lifestyle medicine

Fundamental Clinical Imbalances : Neurological ; Digestive, absorptive and microbiological
Patient Centred Factors : Mediators/Microbiome
Environmental Inputs : Psychosocial influences ; Microorganisms
Personal Lifestyle Factors : Stress and resilience ; Psychological
Functional Laboratory Testing : Saliva ; Stool
Bioactive Substances : Bifidobacterium longum NCC3001 ; Probiotics

Methodological quality

Jadad score : 4
Allocation concealment : Yes


Nutrition Evidence keywords : Microbiome ; Stress