Bifidobacterium longum 1714™ Strain Modulates Brain Activity of Healthy Volunteers During Social Stress

Abstract

Objectives: Accumulating evidence indicates that the gut microbiota communicates with the central nervous system, possibly through neural, endocrine, and immune pathways, and influences brain function. B. longum 1714™ has previously been shown to attenuate cortisol output and stress responses in healthy subjects exposed to an acute stressor. However, the ability of B. longum 1714™ to modulate brain function in humans is unclear.

Methods: In a randomized, double-blinded, placebo-controlled trial, the effects of B. longum 1714™ on neural responses to social stress, induced by the "Cyberball game," a standardized social stress paradigm, were studied. Forty healthy volunteers received either B. longum 1714™ or placebo for 4 weeks at a dose of 1 × 10 cfu/d. Brain activity was measured using magnetoencephalography and health status using the 36-item short-form health survey.

Results: B. longum 1714™ altered resting-state neural oscillations, with an increase in theta band power in the frontal and cingulate cortex (P < 0.05) and a decrease in beta-3 band in the hippocampus, fusiform, and temporal cortex (P < 0.05), both of which were associated with subjective vitality changes. All groups showed increased social stress after a 4-week intervention without an effect at behavioral level due to small sample numbers. However, only B. longum 1714™ altered neural oscillation after social stress, with increased theta and alpha band power in the frontal and cingulate cortex (P < 0.05) and supramarginal gyrus (P < 0.05).

Discussion: B. longum 1714™ modulated resting neural activity that correlated with enhanced vitality and reduced mental fatigue. Furthermore, B. longum 1714™ modulated neural responses during social stress, which may be involved in the activation of brain coping centers to counter-regulate negative emotions.

Figure 1.

Schematic outline of a trial in the Cyberball Game (CBG).

Figure 2.

The CONSORT flow diagram of the clinical trial. Reprinted from Schulz et al. Copyright BMJ (48). All permission requests for this image should be made to the copyright holder.

Figure 3.

Neural activities in different frequency bands during exclusion vs inclusion condition. (a) Theta frequency band (6 Hz): increased power in the bilateral cerebellum (CBL), right middle and inferior frontal cortex (MFC and IFC), left fusiform cortex (P = 0.004); decreased power in the left middle frontal and bilateral superior frontal cortex (SFC) (P = 0.02). (b) Alpha frequency band (11 Hz): increased power in the bilateral CBL, left fusiform, right inferior occipital cortex (P = 0.002); decreased power in the right SFC (P < 0.05). (c) Beta-1 frequency band (16 Hz): increased power in the bilateral CBL, left MFC, left inferior temporal, right middle and superior temporal cortex, and right parahippocampal (P = 0.004). (d) Beta-2 frequency band (21 Hz): increased power in the right CBL, left IFC, right inferior and middle temporal cortex (MTC) (P = 0.002). (e) Beta-3 frequency band (26 Hz): increased power in the bilateral CBL, right fusiform, left parahippocampal, left MTC (P = 0.04).

Figure 4.

Difference of neural activity change during resting state comparing B. longum 1714™ vs placebo. (a) After the intervention, an increased theta band (6 Hz) power was obtained in a cluster including regions of bilateral inferior frontal cortex, middle frontal cortex, and the bilateral anterior cingulate cortex and middle cingulate cortex, comparing B. longum 1714™ with the placebo group (P < 0.05). (b) After the intervention, reduced beta-2 band (26 Hz) power was obtained in a cluster, consisting of the bilateral fusiform gyrus and hippocampus, left inferior temporal cortex and superior temporal cortex, bilateral middle temporal cortex and left cerebellum, comparing B. longum 1714™ with the placebo group (P < 0.05).

Figure 5.

Correlation between neural activity change during resting state and SF36 change. (a) In all groups, a positive correlation was obtained between changes of SF36 item “Energy/vitality” with changes of theta band power in the cluster (r = 0.33, P = 0.04). (b) In only B. longum 1714™ group, changes of SF36 item “Energy/vitality” positively correlated with change of averaged theta band power (r = 0.61, P = 0.007), and negatively correlated with change of beta-3 band power in the activated clusters during the resting state, respectively (r = −0.50, P = 0.04). SF36, 36-item short-form health survey.

Figure 6.

Main effects of condition on NTS and SEP. Participants in all groups reported increased scores of NTS and SEP in the exclusion condition compared with inclusion condition, after a 4-week intervention. MQ, mood questionnaire; NTS, Need Threat Scale; SEP, subjective exclusion perception.

Figure 7.

Difference in neural activity change during the Cyberball game comparing B. longum 1714™ vs placebo. (a) Theta band showed an increased power in a cluster, consisting of the right inferior frontal cortex (IFC) and the bilateral middle frontal cortex (MFC) and superior frontal cortex (SFC), the left anterior cingulate cortex (ACC), the bilateral middle cingulate cortex (MCC), and the right supramarginal gyrus (SMG), comparing B. longum 1714 group and the placebo group in both conditions (P = 0.03). (b) Alpha band power also showed an increased power in cluster, including regions of the right IFC, the bilateral MFC and SFC, the bilateral ACC and MCC, and the right SMG, comparing B. longum 1714™ group and the placebo group in both conditions (P = 0.04). No main effects of condition or interaction of intervention and condition were observed.

Figure 8.

Correlation between neural activity change during the Cyberball game and subjective score changes. Only in B. longum 1714™ group and only during the exclusion condition, NTS changes positively correlated with changes of the theta band power (r = 0.62, P = 0.008) and alpha band power (r = 0.54, P = 0.03). NTS, Need Threat Scale.