Probiotics drive gut microbiome triggering emotional brain signatures

Abstract

Experimental manipulation of the gut microbiome was found to modify emotional and cognitive behavior, neurotransmitter expression and brain function in rodents, but corresponding human data remain scarce. The present double-blind, placebo-controlled randomised study aimed at investigating the effects of 4 weeks' probiotic administration on behavior, brain function and gut microbial composition in healthy volunteers. Forty-five healthy participants divided equally into three groups (probiotic, placebo and no intervention) underwent functional MRI (emotional decision-making and emotional recognition memory tasks). In addition, stool samples were collected to investigate the gut microbial composition. Probiotic administration for 4 weeks was associated with changes in brain activation patterns in response to emotional memory and emotional decision-making tasks, which were also accompanied by subtle shifts in gut microbiome profile. Microbiome composition mirrored self-reported behavioral measures and memory performance. This is the first study reporting a distinct influence of probiotic administration at behavioral, neural, and microbiome levels at the same time in healthy volunteers. The findings provide a basis for future investigations into the role of the gut microbiota and potential therapeutic application of probiotics.

Keywords: Emotional decision; behavior; fMRI; microbiome; probiotics; recognition, memory; stool.

Figure 1.

Schematic representation of multiparametric study design.

Figure 2.

Behavioral results showing, (a) Leiden index of depression severity (LEIDS) scores, (b) PANAS scores (positive and negative), (c) decision change for the emotional decision-making task, (d) the mean response accuracy change (RAU) (for unpleasant stimuli) in the emotional recognition memory task.Error bars indicate for a, b (+/−SE) and for c, d (+/−SD). (AGG – aggression; HOP – hopelessness; ACC – acceptance; CON – control; RAV – risk aversion; RUM – ruminance; *p value ≤ 0.05).

Figure 3.

Emotional decision-making (ED) task. Regions showing differences in neural activity in the PRP group as compared to control groups, for N>B contrast (ΔPRP>ΔPLP, ΔNI >ΔPRP), and U>B contrast (ΔPLP>ΔPRP). Results are reported at p < 0.05 corrected for multiple comparisons using Alphasim corrections. (AnC: anterior cingulum; SFG: superior frontal gyrus).

Figure 4.

Emotional recognition memory (ER) task. Regions showing differences in neural activity in the PRP group as compared to control groups, a) N>B contrast, b) U>B contrast. Results are reported at p < 0.05 corrected for multiple comparisons using Alphasim corrections. (LG: Lingual gyrus; CG: Calcarine gyrus; AnC: anterior cingulum).

Figure 5.

Microbiome analysis showing, (a) PCoA (Principal Coordinates Analysis) plot (to explore and visualize similarities and dissimilarities of the microbiome data of different samples) based on microbial OTUs of control group, placebo group (PLP) and product group (PRP), Bray-Curtis distance, (b) RDA (Redundancy Analysis) plot of PLP (placebo group) versus PRP (product group) after administration.

Figure 6.

Schematic representation of the experimental fMRI tasks: (a) emotional decision-making task, (b) emotional recognition memory task.