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Dried Blood Spot Collection of Health Biomarkers to Maximize Participation in Population Studies
Published on: January 28, 2014
Biomarkers
Alexis B Kazen1, Laura Glass Umfleet1, Fatima A Aboulalazm1
1Medical College of Wisconsin, Wauwatosa, WI, USA.
Background:
Gut dysbiosis and cerebrovascular disease have both been implicated in Alzheimer's disease (AD) progression and pathophysiology. However, the interplay between them is unclear. The goal of this study was to identify relationships between gut microbiota (GMB), cerebrovascular functioning, and cognition in patients diagnosed with amnestic mild cognitive impairment (aMCI) compared to cognitively unimpaired older adult controls.
Methods:
Participants (N = 14 aMCI and 10 controls) provided fecal samples for 16S and shotgun metagenomics GMB sequencing, underwent an MRI, and completed neuropsychological tests. For MRI, cerebral vascular reactivity (CVR), cerebral blood flow (CBF) and arterial transit time (ATT) were assessed. Spearman rho correlational analysis was used to evaluate relationships between discriminatory microbial taxa, cerebrovascular metrics, and cognition.
Results:
Sequencing revealed differentially abundant bacterial and viral taxa distinguishing aMCI from controls. Spearman correlations revealed that bacteria known to induce inflammation were negatively associated with cognition and cerebrovascular function, whereas bacteria associated with a healthy gut microbiome had positive associations with cognitive and cerebrovascular function. For example, Alistipes indistinctus, which depletes intestinal urate levels was enriched in aMCI and had significant negative correlations with Trail Making Test-B (TMT-B; rs=-.587) and category fluency (CF) scores (rs=-.422), CVR (rs=-.437), and CBF (rs=-.546). Bilophila wadsworthia was negatively associated (trend-level) with CVR and CBF, and significantly correlated with TMT-B (rs = -.499) and category fluency (rs = -.503). The bile acid modifying bacterium, Turicibacter sp., had a significant positive correlation with CBF (rs=.423). Finally, we found that several bacteriophages had significant correlations with cognitive and cerebrovascular measures, such as a B. wadsworthia phage that was enriched in aMCI and had significant negative correlations with TMT-B (rs=-.491), delayed recall (rs=-.589), and CVR (rs=-.474). Further, this phage contained an acyl-coA synthetase capable of influencing central metabolism.
Conclusions:
Consistent with previous research, we found that persons with aMCI have an altered gut microbiome relative to controls. Further, we demonstrate through metagenomics sequencing that both bacterial and viral taxa are associated with cognitive and neurovascular functioning in aMCI. Knowledge about the relationships between the microbiota, cognition, and cerebrovascular function paves the way for future studies cross-sectional and longitudinal studies.
Insights
Alterations in the gut microbiome, including bacteria and viruses, are linked to cognitive decline and cerebrovascular changes in mild cognitive impairment. Specific gut microbes and phages correlate with brain function and health.
Area of Science:
- Neuroscience
- Microbiology
- Gastroenterology
Background:
- Alzheimer's disease (AD) is associated with gut dysbiosis and cerebrovascular disease, but their interaction is not fully understood.
- Investigating the gut microbiota's role in mild cognitive impairment (MCI) is crucial for understanding AD pathophysiology.
Purpose of the Study:
- To explore the relationship between gut microbiota composition, cerebrovascular function, and cognitive status in individuals with amnestic mild cognitive impairment (aMCI).
- To compare gut microbiota profiles and cerebrovascular metrics between aMCI patients and cognitively unimpaired controls.
Main Methods:
- 14 aMCI patients and 10 controls provided fecal samples for 16S and shotgun metagenomics sequencing.
- Cerebral vascular reactivity (CVR), cerebral blood flow (CBF), and arterial transit time (ATT) were assessed using MRI.
- Spearman correlation analysis examined links between microbial taxa, cerebrovascular metrics, and cognitive scores.
Main Results:
- Distinct bacterial and viral taxa differentiated aMCI patients from controls.
- Pro-inflammatory gut bacteria negatively correlated with cognition and cerebrovascular function; beneficial bacteria showed positive associations.
- Specific microbes like Alistipes indistinctus and Bilophila wadsworthia, and a B. wadsworthia phage, were linked to poorer cognitive and cerebrovascular outcomes in aMCI.
Conclusions:
- Individuals with aMCI exhibit altered gut microbiomes compared to controls.
- Both bacterial and viral gut microbes are significantly associated with cognitive and neurovascular function in aMCI.
- Understanding these gut-brain-vasculature axis interactions can inform future research on MCI and AD.
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