Probiotic Supplementation Improves Cognitive Function and Mood with Changes in Gut Microbiota in Community-Dwelling Older Adults: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial

Abstract

Probiotics have been proposed to ameliorate cognitive impairment and depressive disorder via the gut-brain axis in patients and experimental animal models. However, the beneficial role of probiotics in brain functions of healthy older adults remains unclear. Therefore, a randomized, double-blind, and placebo-controlled multicenter trial was conducted to determine the effects of probiotics on cognition and mood in community-dwelling older adults. Sixty-three healthy elders (≥65 years) consumed either placebo or probiotics containing Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI for 12 weeks. The gut microbiota was analyzed using 16S rRNA sequencing and bioinformatics. Brain functions were measured using the Consortium to Establish a Registry for Alzheimer's disease, Satisfaction with life scale, stress questionnaire, Geriatric depression scale, and Positive affect and negative affect schedule. Blood brain-derived neurotrophic factor (BDNF) was determined using enzyme-linked immunosorbent assay. Relative abundance of inflammation-causing gut bacteria was significantly reduced at Week 12 in the probiotics group (p < .05). The probiotics group showed greater improvement in mental flexibility test and stress score than the placebo group (p < .05). Contrary to placebo, probiotics significantly increased serum BDNF level (p < .05). Notably, the gut microbes significantly shifted by probiotics (Eubacterium and Clostridiales) showed significant negative correlation with serum BDNF level only in the probiotics group (RS = -0.37, RS = -0.39, p < .05). In conclusion, probiotics promote mental flexibility and alleviate stress in healthy older adults, along with causing changes in gut microbiota. These results provide evidence supporting health-promoting properties of probiotics as a part of healthy diet in the older adults.

Keywords: Cognitive function; Gut microbiota; Healthy older adults; Mood status; Probiotics; RCT.

Figure 1.

Beneficial influence of probiotic supplementation on intestinal health and gut microbiota. (A,B) Improvement scores in frequency of gas passage and abdominal distention measured at each visit are shown. Data are presented as mean (SEM). (C) Relative abundance of the gut microbiota at the phylum level and (D–G) at the genus level was measured throughout the intervention. Data are presented as mean (min-max). ^#p < .05 based on the Mann–Whitney U test; ^**p < .005, *p < .05 based on a post hoc analysis of Friedman test.

Figure 2.

Improved cognitive and mental functioning after probiotic supplementation. (A) Change from baseline of cognitive performance score in the mental flexibility test is shown. Reduction in the performance score of mental flexibility indicates improved attention and executive function. (B) Change from baseline of stress level is shown. Reduction in the change indicates a reduced level of mental stress. Data are presented as mean (SEM). *p < .05 based on the Mann–Whitney U test for the comparison analysis of changes from baseline between the two groups.

Figure 3.

Elevated level of serum BDNF after probiotic supplementation. (A) Change from baseline of serum BDNF is shown. Data are presented as mean (SEM). *p < .05 for time × treatment from a mixed-model analysis of variance. (B) Scatter diagrams with regression lines show the relationship between relative abundance of shifted gut bacteria after probiotic supplementation and the level of serum BDNF. Measurements were rank-normalized and plotted separately for the placebo and probiotics group. Correlation coefficient (R_S) and p-values based on Spearman rank correlation analysis. BDNF = Brain-derived neurotrophic factor.