Mental awareness improved mild cognitive impairment and modulated gut microbiome

Abstract

There is ample scientific and clinical evidence of the effects of gut microbiota on the brain but no definitive evidence that the brain can affect changes in gut microbiota under the bi-directional gut-brain axis concept. As there is no pharmacotherapeutic intervention for the early stages of cognitive decline, research has focused on cognitive stimulation in reversing or slowing the impairment. Elderly patients diagnosed with mild cognitive impairment underwent a randomized-control trial of mindful awareness practice. Neuropsychological assessments, inflammatory markers, and gut microbiota profiles were tested. Here, we report that their cognitive impairment was improved and associated with changes in gut bacterial profile. A cognition-score-dependent-abundance was observed in Ruminococcus vs Recognition Trials (RT), Digit Span Backward (DSB), Semantic Fluency Span (SFS) and Memory Domain (MD); Coprococcus vs DSB, Color Trails Test 2 (CTT2) and Block Design (BD); Parabacteroides vs DSB and SFS; Fusobacterium vs DSB and CTT2; Enterobacteriaceae vs BD and SFS; Ruminococcaceae vs DSB; Phascolarctobacterium vs MD. The study showed for the first-time, alteration in the cognitive capacity leading to the corresponding changes in microbiota profiles. This strongly suggests that signals from the different segments of brain could dictate directly or indirectly the abundances of specific gut microbes.

Keywords: gut-brain axis; mental health; microbiome; mild cognitive impairment; mindful awareness practice.

Conflict of interest statement

CONFLICTS OF INTEREST: The authors declare no conflicts of financial interests.

Figures

Figure 1

(A, B) The distribution of microbiota profiles among Normal Aging and Mindful Awareness Program (MAP) groups. (A) A distance-based redundancy analysis (db-RDA) plot. (B) species biplot describes 1 % and above of the bacterial genera distribution in the db-RDA plane. The groups of the subjects are represented by four different color-coded symbols with sample size in parenthesis in the legend.

Figure 2

Alpha and beta diversity of Normal Aging and MAP groups. (A) Chao 1’s, (B) Shannon’s alpha diversity indexes comparing Normal Aging and three time points of MAP groups. p* values of Mann-Whitney U test described significant difference from each other at two-sided p values of 0.05. In each box plot, median line, + mean, upper and lower quartiles, upper and lower extremes and whiskers are presented. (C) Weighted (D) Unweighted Unifrac principal coordinates analysis (PCoA) for beta diversity comparing Normal Aging and three time points of MAP groups. The groups of the subjects are represented by four different color-coded symbols with sample size in parenthesis in the legend. MAP= Mindful Awareness Program.

Figure 3

Nutritional intake of Normal Aging and MCI subjects. Overall nutritional intake comparing two groups of the subject. Two-tailed p values calculated by non-parametric Mann-Whitney U-test were described in the individual box plots and presented as ** p ≥ 0.001 - < 0.01, * p ≥ 0.01- < 0.05. In each box plot, median line, + mean, upper and lower quartiles, upper and lower extremes and whiskers are presented. The groups of the subjects are represented by two different color-coded symbols with sample size in parenthesis in the legend. MCI= Mild cognitive impairment.

Figure 4

Neuropsychological tests of MCI subjects, which showed differences with Normal Aging subjects, and during MAP intervention study. Significant different p values (two-tailed, at p= 0.05) of Mann-Whitney U test are described comparing two groups and presented as **** p < 0.0001, *** p ≥ 0.0001 - < 0.001, ** p ≥ 0.001 - < 0.01, * p ≥ 0.01- < 0.05. In each box plot, median line, + mean, upper and lower quartiles, upper and lower extremes and whiskers are presented. The groups of the subjects represented by four different color-coded symbols with sample size are indicated in parenthesis in the legend. MCI= Mild cognitive impairment, MAP= Mindful awareness program.

Figure 5

Comparison of four blood biomarkers in Normal Aging and MAP groups. (A) Mean of telomere length over time in the MAP intervention study. P values were calculated by Wilcoxon matched-pairs signed-rank t test comparing the two groups. The samples of Normal Aging were not measured for telomere length. (B) Concentrations of BDNF (pg/ml), (C) DHEAS (ng/ml) and (D) hs-CRP (μg/ml) comparing Normal Aging and three timepoints of MAP groups. Significant different two-tailed p values of Mann-Whitney U test are presented as **** p < 0.0001, *** p ≥ 0.0001 - < 0.001, ** p ≥ 0.001 - < 0.01, * p ≥ 0.01- < 0.05. In each box plot, median line, + mean, upper and lower quartiles, upper and lower extremes and whiskers are presented. The groups of the subjects represented by three different color-coded symbols with sample size are indicated in parenthesis in the legend. MAP= Mindful Awareness Program, BDNF= Brain-derived neurotrophic factor, DHEAS= Dehydroepiandrosterone sulfate, hs-CRP= High sensitive C-reactive protein.

Figure 6

Comparison of fecal water cytokines in Normal Aging and MAP groups. Concentration of 11 fecal water cytokines (pg/ml) are described in each box plot comparing Normal Aging and three timepoints of MAP groups. Significant different two-tailed p values of Mann-Whitney U test are presented as **** p < 0.0001, *** p ≥ 0.0001 - < 0.001, ** p ≥ 0.001 - < 0.01, * p ≥ 0.01- < 0.05. In each box plot, median line, + mean, upper and lower quartiles, upper and lower extremes and whiskers are presented. The groups of the subjects represented by three different color-coded symbols with sample size are indicated in parenthesis in the legend. MAP= Mindful awareness program, IL= Interleukin, IL-1β= Interleukin-1 beta, TNFα= Tumor necrosis factor alpha, IFNγ= Interferon gamma, GM-CSG= Granulocyte-macrophage colony-stimulating factor.

Figure 7

Correlation between Z scores of neuropsychological tests and relative abundances of major gut bacterial genus (>1% of total OTU) of three timepoints of MAP groups. In the heatmap, Spearman correlation coefficient rho (r) are presented in red (positive correlation), white (no correlation) and green (negative correlation). The significant different correlations are presented as **** p < 0.0001, *** p ≥ 0.0001 - < 0.001, ** p ≥ 0.001 - < 0.01, * p ≥ 0.01- < 0.05. The p values were corrected by false discovery rate using the Benjamini and Hochberg method and q values were represented as # q ≥ 0.01- < 0.05. OTU= Operational taxonomical unit, MAP= Mindful awareness program, UG= Unknown genus, UF= Unknown family. MAP (both correlation parameters); n= 53 (Timepoint 1; n= 28, Timepoint 2; n= 21, Timepoint 3; n= 14).