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

Abstract

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.

Keywords: cortisol; gut–brain axis; probiotic; psychological stress; sleep.

Figure 1

CONSORT flowchart depicting the progression of participants through the study. DASS-42, Depression, Anxiety and Stress Scale; SAF, Safety Analysis Set; FAS, Full Analysis Set.

Figure 2

Effects of 6 weeks of intervention with BL NCC3001 in healthy adults with self-reported mild-to-moderate stress. (a) Probiotic intervention significantly increased the abundance of BL NCC3001 in stool. *** p < 0.001; (b) probiotic intervention significantly decreased the level of perceived stress as measured by PSS-14. Depiction of delta change post-intervention vs. baseline. * p < 0.05. (c) Principal Component Analysis (PCA) biplot on the z-scores of the baseline-to-post-intervention difference of heart rate (HR_Stressor) and PSS-14 (Stress) as active variables and all others as passive variables. This biplot simultaneously visualizes the correlation structure between active and passive variables as well as the multivariate positioning of individual subjects, with those in the probiotic intervention group being differentially marked according to the quartile they belong to in terms of detected probiotics. Smallest ellipses featuring 80% subjects are given for both groups.

Figure 3

Differential cortisol response at waking and to acute stress: (a) cortisol awakening response; (b) cortisol response to acute stress. * p < 0.05.

Figure 4

Impact of the probiotic intervention on subject mood assessments linked to acute stress response. (a) Placebo group significantly increased positive PANAS change score from pre-stressor stage with higher scores for the placebo group compared to the probiotic group. ** p < 0.01.(b) Lower values of VAS Painful change score from pre-stressor to post-stressor in the probiotic group. * p < 0.05.