Association between Gut Microbiota with Mild Cognitive Impairment and Alzheimer’s Disease in a Thai Population

Abstract

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.

Altered gut microbiota in older adults with mild cognitive impairment: a case-control study

“…MCI patients with more Bacteroides are more likely to present brain atrophy patterns compatible with AD ( Saji et al, 2019a ). Regarding regional brain volume, Wanapaisan et al have discovered associations of left and right-hippocampus and right amygdala volumes with groups of bacteria identified in their study ( Wanapaisan et al, 2022 ). However, they also enrolled AD patients and mainly compared brain volumes in controls with AD/MCI.…”

“…Studies in AD have demonstrated a microbial composition that deviates significantly from that of cognitively normal controls ( Vogt et al, 2017 ; Zhuang et al, 2018 ; Liu et al, 2019 ; Saji et al, 2019a , b ; Guo et al, 2021 ). There is also emerging data about gut microbiota change in MCI patients ( Li et al, 2019 ; Liu et al, 2019 ; Saji et al, 2019a , b ; Guo et al, 2021 ; Pan et al, 2021 ; Sheng et al, 2021 , 2022 ; Zhang et al, 2021 ; Verhaar et al, 2022 ; Wanapaisan et al, 2022 ; Yıldırım et al, 2022 ). In general, similar gut microbiota changes as AD were found in MCI patients, such as decreased Bacteroides genus and increased Staphylococcus and Escherichia ( Li et al, 2019 ; Nagpal et al, 2019 ).…”

Pathways linking microbiota-gut-brain axis with neuroinflammatory mechanisms in Alzheimer’s pathophysiology

“…While Pseudomonadota tends to generally be overrepresented in AD and MCI patients, certain studies suggest somewhat contradictory evidence as some research observed negative correlations between genera such as Sutterella and AD/MCI [ 82 , 83 ] while others observed their positive correlations to AD/MCI [ 52 , 81 , 84 ] . Other genera such as Escherichia/Shigella and Klebsiella are consistently elevated in AD/MCI patients where differences reach significance [ 54 , 81 , 82 , 85 , 86 ] . The general trend of Pseudomonadota overrepresentation in AD/MCI patients may be reflective of the proinflammatory characteristics of LPS; however, inconsistencies such as those found in relative Sutterella abundance may be reflective of other important factors such as differential bacterial metabolic processes at the genus, species, or even strain level and thus effects on host inflammation.…”

Association Analysis of Gut Microbiota and Prognosis of Patients with Acute Ischemic Stroke in Basal Ganglia Region

“…It was significantly decreased in PD with more intensive inflammation in the intestine [45], which was further identified as a critical biomarker of the progression of PD in another study [46]. In a study of the Thai population, the abundance of Fusicatenibacter was dramatically downregulated in dementia patients [47]. According to the evidence above, we assumed that these two genera contributed to the maintenance of gut-brain axis in relatively healthy individuals and had a positive impact on the recovery of BGRI.…”