The Link Between Oxysterols and Gut Microbiota in the Co-Dysfunction of Cognition and Muscle

Abstract

Background/Objectives: Alterations of oxysterols and gut microbiota have been recognized as indicators affecting mild cognitive impairment (MCI) and sarcopenia, respectively, whereas their association with co-dysfunction has not been investigated. Methods: In this study, a total of 1035 individuals were divided into Control (n = 264), MCI (n = 435), and MCI with possible sarcopenia (MPS, n = 336) groups. Cognition and muscle indexes, serum oxysterols, and gut microbiota were measured. Spearman's rank coefficients were calculated to determine their correlations. Results: Performances of global and multidimensional cognitive tests was successively worse in the Control, MCI, and MPS groups. Longer duration of five-time chair stand test, lower 6-meter walk speed, and handgrip strength were observed in the MPS group, along with increased 27-hydroxycholesterol (27-OHC) and 5α,6α-epoxycholesterol and decreased 5α-Cholest-8(14)-ene-3β,15α-diol (15-HC). Higher concentrations of amyloid precursor protein (APP), neurofilament, and C-terminal agrin fragment (CAF) were discovered in the MCI and MPS groups. The α-diversity of gut microbiota in the MCI and MPS group was remarkably decreased, followed by a shifted abundance of microbial taxa, such as Alistipes and Rikenellaceae. Multiple significant correlations were found between cognition and muscle indexes and with oxysterols. Conclusions: Our study indicates that oxysterols and gut microbiota are prominently involved in the co-dysfunction of cognition and muscle.

Keywords: comorbidity; gut microbiota; mild cognitive impairment; muscle function; oxysterols.

Figure 1

Flow chart of detailed recruitment in the study. MCI, mild cognitive impairment; MPS, MCI with possible sarcopenia.

Figure 2

Serum biomarkers detected using ELISA. (A) Amyloid precursor protein (APP), (B) amyloid-β (Aβ1-42), (C) neurofilament (Nfl), (D) C-terminal agrin fragment (CAF), (E) irisin, and (F) brain-derived neurotrophic factor (BDNF). * p < 0.05, ** p < 0.01.

Figure 3

Gut microbiota composition among Control, MCI, and MPS group. (A) Venn diagram illustrating the amount of ASVs. Relative abundance of top ten taxa on the level of (B) phylum, (C) class, (D) order, (E) family, and (F) genus.

Figure 4

Different relative abundance of bacterial taxa using t-test. Taxa were presented in the level of (A) phylum, (B) class, (C) order, (D) family (Control vs. MPS), (E) family (MCI vs. MPS), (F) family (Control vs. MCI), (G) genus (Control vs. MPS), (H) genus (MCI vs. MPS), and (I) genus (Control vs. MCI). p < 0.05 were considered significant.

Figure 5

Microbial diversity and cladogram. The α-diversity of the fecal microbiome including (A) Chao 1, (B) Observed_otus, (C) Shannon, and (D) Simpson was analyzed using the Wilcoxon rank-sum test. The β-diversity was analyzed using PCOA (E) and NMDS (F) on the basis of weighted UniFrac distance. * p < 0.05, ** p < 0.05.

Figure 6

Linear discriminant analysis (LDA) effect size (LEfSe) analysis classifying the taxonomic differences among groups. The cutoff value of the LDA was 3.0, with p < 0.05 showing significant values.

Figure 7

Cladogram of bacterial signatures based on differential gut microbial taxa from LEfSe analysis.

Figure 8

Correlation between the indexes of cognition and muscle using Spearman’s correlation coefficient. The strength of association is represented by color.

Figure 9

Correlation between oxysterols and cognition indexes using Spearman’s correlation coefficient. The strength of association is represented by color.

Figure 10

Correlation between oxysterols and muscle indexes using Spearman’s correlation coefficient. The strength of association is represented by color.