Abstract
Intestinal microbiota may play a significant role in the development and progression of mild cognitive impairment (MCI). In addition, sex differences in the prevalence of MCI and intestinal microbiota are likely to exist. Therefore, this study investigated the association between MCI and intestinal microbiota by comparing Japanese patients in their 70s with MCI (11 males and 18 females) and disease-free controls (17 males and 23 females), taking sex into account. In both sexes, Clostridium_XVIII, Eggerthella, Erysipelatoclostridium, Flavonifractor, and Ruminococcus 2 were the more abundant taxa in the MCI group, whereas Megasphaera, Oscillibacter, Prevotella, Roseburia, and Victivallis were less abundant. Based on these characteristics, it was hypothesized that the composition of the intestinal microbiota in the MCI group leads to dysregulation of the intestinal microbiota, increased intestinal and blood-brain barrier permeability, and increased chronic neuroinflammation, with the long-term persistence of these abnormalities ultimately leading to cognitive decline. Furthermore, risk estimation models for MCI based on intestinal microbiota data were developed using structural equation modeling. These tests discriminated between the MCI and control groups. Incorporating these factors into intestinal microbiota testing using stool samples may be an efficient method to screen individuals with MCI.