Characteristics of Intestinal Microbiota in Japanese Patients with Mild Cognitive Impairment and a Risk-Estimating Method for the Disorder

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.

A risk estimation method for depression based on the dysbiosis of intestinal microbiota in Japanese patients

“…Stool sample collection, DNA extraction, and 16S rRNA gene sequence (variable regions V1 to V3) analysis using the MiSeq system (Illumina, San Diego, CA, USA) followed the method described by Hatayama et al. ( 14 ). Stool samples were self-collected by participants using a stool collection kit (Techno-Suruga Laboratory Co., Ltd., Shizuoka, Japan) and were mailed to the laboratory without freezing or refrigeration.…”

“…The genus-level ASV table was rarefied based on the sequence coverage ( 21 ) (slope: 0.002259329 or less) using vegan v. 2.5.7 package ( 22 ) in R. The α-diversity analyses and comparison of intestinal microbiota between groups using the ANOVA-like differential expression tool (ALDEx2) ( 23 – 25 ) were conducted according to Hatayama et al. ( 14 ). The centered log ratio (CLR)-transformed intestinal microbiota data were used for the ALDEx2 comparison.…”

“…The details of its construction are described by Hatayama et al. ( 14 ). The SEM was constructed using the CLR-transformed intestinal microbiota by ALDEx2 and depression incidence data.…”

“…Estimating disease risk based on intestinal microbiota composition using structural equation modeling (SEM) has been previously reported. Risk-estimation methods have been developed for atopic dermatitis and mild cognitive impairment based on their association with intestinal microbiota ( 13 , 14 ). Therefore, this method could provide a risk-estimation model for depression which could subsequently be a promising predictive method for depression if indeed the risk of depression is associated with intestinal microbiota.…”

Characteristics of the gut microbiota of patients with symptomatic carotid atherosclerotic plaques positive for bacterial genetic material

“…Species of Clostridium_sensu_stricto_1 are linked to various infectious diseases (Gubler et al, 1989;Tappe et al, 2009;Daganou et al, 2016), and there have been case reports of Romboutsia causing human marrow necrosis (Seviar et al, 2022), suggesting these genera may have certain adhesive and colonization capabilities (Boyle and Finlay, 2003). Mucins play a significant role in the gut barrier mechanism (Breugelmans et al, 2022), and Ruminococcus_2 is associated with their degradation (Hatayama et al, 2023), indicating that this genus might translocate by disrupting the integrity of the gut barrier. Anaerococcus, commonly residing in the skin and gastrointestinal tract, can cause infections and lead to bacteremia under certain conditions (Murphy and Frick, 2013;Badri et al, 2019;Cobo et al, 2021), indicating its adhesive and colonization capabilities.…”