Diet Quality, Gut Microbiota, and MicroRNAs Associated with Mild Cognitive Impairment in Middle-aged and Elderly Chinese Population

Background: Diet, the gut microbiota, and microRNAs (miRNAs) have been recognized as factors possibly influencing the pathogenesis of Alzheimer's disease. However, the combined role of diet, the gut microbiota, and miRNAs in mild cognitive impairment (MCI) has not been extensively investigated.

Objectives: To examine the associations among diet quality, the gut microbiota, miRNAs, and risks of MCI in middle-aged and elderly Chinese population.

Methods: Participants were drawn from the Effects and Mechanism Investigation of Cholesterol and Oxysterol on Alzheimer's disease (EMCOA) study. We included 2239 participants who completed comprehensive cognitive tests and dietary surveys at baseline and follow-up. Chinese Dietary Guidelines Index 2018 (CDGI-2018), Energy-Adjusted Dietary Inflammatory Index (E-DII) and Healthy Lifestyle Score (HLS) values were calculated based on data from a standard questionnaire. Changes of gut microbiota and serum miRNA expression were detected in 75 MCI and 52 healthy participants. The receiver operating characteristic curve was performed based on a logistic regression model distinguishing patients with MCI from healthy controls.

Results: Higher CDGI-2018 (RR, 0.75; 95% CI: 0.58-0.98) and HLS (RR, 0.54; 95% CI: 0.34-0.84) values and lower E-DII (RR, 1.46; 95% CI: 1.14-1.87) values were significantly associated with a lower risk of MCI. Lower microbial diversity and abundance of Faecalibacterium, unidentified Ruminococcaceae, and Alistipes were found in MCI participants compared with healthy controls. The abundance of ProteobacteriaandGammaproteobacteria was higher in MCI participants and was correlated with hsa-let-7g-5p, hsa-miR-107, and hsa-miR-186-3p. The predictive signatures of diet quality scores, differential gut microbiota, and serum miRNAs had good performance on distinguishing MCI participants from healthy individuals (AUC = 0.91).

Conclusions: A better diet quality is associated with a lower risk of MCI, which may be mediated by the microbiota composition and miRNA expression. These findings suggest that diet, the gut microbiota, and miRNAs may serve as a combinatorial biomarker to identify MCI patients and provide new insight for the diagnosis and prevention of MCI. This study was registered at the Chinese Clinical Trial Registry as ChiCTROOC-17011882.