Background: Mild cognitive impairment (MCI) and Alzheimer's disease (AD) are common in older adults. Much recent work has implicated the connection between the gut and the brain via bidirectional communication of the gastrointestinal tract and the central nervous system through biochemical signaling. Altered gut microbiota composition has shown controversial results based on geographic location, age, diet, physical activity, psychological status, underlying diseases, medication, and drug use. Objectives: This study aimed to investigate the relationships of gut microbiota with MCI and AD. Methods: 16S metagenome profiles from stool collection of participant groups (normal; n=20, MCI; n= 12, AD; n=20) were analyzed. The diagnosis of cognitive conditions was made by standard criteria consisting of clinical interviews, physical examinations, cognitive assessments, laboratory examinations, and neuroimaging by both structural neuroimaging and amyloid positron emission tomography scans. Correlations between medical factors with food frequency and the fecal microbiome were elucidated. Results: A significant difference at the operational taxonomic unit level was observed. The significantly higher abundance of bacteria in nondementia patients belonged to the Clostridiales order, including Clostridium sensu stricto 1 (p<0.0001), Fusicatenibacter (p=0.0007), Lachnospiraceae (p=0.001), Agathobacter (p=0.021), and Fecalibacterium (p<0.0001). In contrast, Escherichia-Shigella (p=0.0002), Bacteroides (p=0.0014), Holdemanella (p<0.0001), Romboutsia (p=0.001), and Megamonas (p=0.047) were the dominant genera in the AD group. Left and right-hippocampus and right amygdala volumes were significantly decreased in the AD group (p < 0.001) and significantly correlated with the groups of bacteria that were significantly different between groups. Conclusion: There was a relationship between the composition of the gut microbiome and neurodegenerative disorders, including MCI and AD. Reduction of Clostidiaceae and increases in Enterobactericeae and Bacteroides were associated with persons with MCI and AD, consistent with previous studies. The altered gut microbiome could be potentially targeted for the early diagnosis of dementia and the reduction of AD risk.
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