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Mild cognitive impairment has similar alterations as Alzheimer's disease in gut microbiota
Binyin Li1, Yixi He1, Jianfang Ma1
1Department of Neurology & Collaborative Innovation Center for Brain Science, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
Objective:
Gut microbiota changes before the onset of Alzheimer's disease (AD) and the alterations could be detected in the stage of mild cognitive impairment (MCI). The findings might offer diagnostic biomarkers before the onset of dementia.
Background:
AD is the most common cause of dementia, and MCI is the predementia state. Recent studies suggest the alterations in the gut microbial communities associated with AD, whereas the microbiota in MCI before the onset of dementia has not been discovered and characterized in humans.
New/Updated Hypothesis:
We hypothesize that the dysbiosis happens in the MCI stage. Patients with AD and MCI have decreased microbial diversity, and changes in gut microbiota could be detected for early detection of AD. In our preliminary study, we identified differences between AD and normal controls in 11 genera from the feces and 11 genera from the blood. No difference in genera between AD and MCI was detected. Using the diagnostic model from fecal samples with all different genera input, 93% (28 in 30) of patients with MCI could be identified correctly.
Major Challenges For The Hypothesis:
The diagnosis of MCI and AD in the study was based on symptoms and neuroimaging, and AD biomarkers should be included for precise diagnosis in further validating studies. Besides, as the microbiota changes longitudinally, their relationship with the progress of dementia needs to be studied in the prospective studies.
Linkage To Other Major Theories:
Escherichia was observed increased at genus level in both fecal and blood samples from AD and MCI. For AD biomarker, postmortem brain tissue from patients with AD showed lipopolysaccharides and gram-negative Escherichia coli fragments colocalize with amyloid plaque. In this way, the amyloid pathogenesis for AD would be triggered during MCI by gut microbiota shifting. Besides, systemic inflammatory reactions caused by compounds secreted by bacteria may impair the blood-brain barrier and promote neuroinflammation and/or neurodegeneration. Furthermore, abnormal metabolites caused by microbial gene functions have an impact on neurodegeneration.
Insights
Changes in gut microbiota may signal early Alzheimer's disease (AD) even in mild cognitive impairment (MCI). These gut microbiome alterations could serve as potential diagnostic biomarkers for early AD detection.
Area of Science:
- Microbiology
- Neuroscience
- Gastroenterology
Background:
- Alzheimer's disease (AD) is a leading cause of dementia, with mild cognitive impairment (MCI) representing its predementia stage.
- While gut microbial alterations are linked to AD, their role in the MCI stage remains under-explored in humans.
Purpose of the Study:
- To investigate gut microbiota changes in individuals with MCI and AD.
- To assess the potential of gut microbial profiles as early diagnostic biomarkers for AD before overt dementia onset.
Main Methods:
- Analysis of fecal and blood samples to identify differences in microbial genera between individuals with MCI, AD, and healthy controls.
- Development of a diagnostic model using fecal microbial data to predict MCI status.
Main Results:
- Decreased microbial diversity was observed in both MCI and AD groups.
- A diagnostic model based on fecal samples correctly identified 93% of MCI patients.
- Increased levels of the Escherichia genus were found in both fecal and blood samples of MCI and AD patients.
Conclusions:
- Gut dysbiosis is present in the mild cognitive impairment stage, preceding Alzheimer's disease.
- Gut microbiota alterations, particularly shifts in specific genera like Escherichia, show promise as early diagnostic biomarkers for AD.
- Further research incorporating AD biomarkers and longitudinal studies is needed to validate these findings and understand the progression of dementia.