Microbial Determinants of Dementia Risk in Type 2 Diabetics of Mexican Descent Living in South Texas: A Pilot Study

Type 2 diabetes (T2D) is a common antecedent of pathological neurodegeneration and accompanying dementia, including Alzheimer's Disease (AD). However, relatively little is known regarding mechanistic links between metabolic and neurodegenerative disorders. We recently completed a pilot clinical study focusing on individuals of Mexican descent living in Southern Texas - a population with increased prevalence of co-morbid T2D and early onset AD - with the working hypothesis that diet-driven shifts in gut microbiome composition contribute to T2D and AD susceptibility and pathophysiology in this population. Gastrointestinal symptom rating scale (GSRS) survey data from study participants provided evidence supporting an altered gut microbial ecology in subjects with T2D (sT2D) compared to healthy controls without T2D (HC), despite no significant differences in dietary preferences. Metagenomic 16S rRNA gene amplicon sequencing of twelve stool samples revealed that T2D gut communities are less diverse than those of HC, as determined by alpha diversity metrics. Furthermore, we observed a significant decrease in the abundance of the immunomodulatory short-chain fatty acid-producing taxa and increased abundance of a known pathobiont in gut microbiomes of sT2D. Our results suggest that characterization of the gut microbiome of individuals with T2D could be used to identify key actors among disease state microbiota which may exacerbate or accelerate neurodegenerative disorders and may point toward novel microbiome-targeted immunotherapeutic approaches for treating neuroinflammation in AD.