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

<b>Background/Objectives:</b> 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. <b>Methods:</b> In this study, a total of 1035 individuals were divided into Control (<i>n</i> = 264), MCI (<i>n</i> = 435), and MCI with possible sarcopenia (MPS, <i>n</i> = 336) groups. Cognition and muscle indexes, serum oxysterols, and gut microbiota were measured. Spearman's rank coefficients were calculated to determine their correlations. <b>Results:</b> 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. <b>Conclusions:</b> Our study indicates that oxysterols and gut microbiota are prominently involved in the co-dysfunction of cognition and muscle.