Microbial Determinants of Dementia Risk in Type 2 Diabetics of Mexican Descent
Condition: Diabetes
MeSH terms: Dementia
Study type: Observational

Summary: 
      Type 2 diabetes (T2D) predisposes individuals to neurodegeneration and dementia, including
      Alzheimer's Disease (AD); yet the link between metabolic and neurodegenerative disorders
      remains unknown. Here, the investigators will study a well-defined human population with
      increased prevalence and early onset of both T2D and AD, individuals of Mexican descent
      living in South Texas. The study will begin to explore the possibility that disruption of the
      structure of the bacterial community residing in the gut in type 2 diabetic individuals of
      Mexican descent living in South Texas is directly related to the increased prevalence of
      early onset AD in this population. In this study, the investigators will perform gene
      sequencing on DNA isolated from fecal samples to identify and compare the populations of
      bacteria living in individuals with T2D versus non-diabetic controls. The investigators will
      analyze the findings to determine if the community structure of the gut microbiome of
      individuals of Mexican descent with T2D is significantly altered compared to that of
      non-diabetics within the same population. The investigators' findings could lead to the
      identification of early indicators of dementia onset as well as novel therapies for treating
      metabolic and neurodegenerative diseases.
    

Detailed description: 
      Type 2 diabetes (T2D) as a common antecedent of pathological neurodegeneration and dementia,
      including Alzheimer's Disease (AD); yet the mechanistic link between metabolic and
      neurodegenerative disorders remains unresolved. Here, the investigators will study a
      well-defined human population with increased prevalence and early onset of both T2D and AD,
      individuals of Mexican descent living in South Texas. The study will lay critical groundwork
      toward addressing the investigators' overarching hypothesis that dysbiosis of the gut
      microbiome in type 2 diabetic individuals of Mexican descent living in South Texas is
      causally related to the increased prevalence of comorbid, early onset AD in this population.
      In this study, the investigators will perform state-of-the-art metagenomic 16S ribosomal RNA
      (rNRA) gene sequencing and bioinformatic analysis on fecal samples collected from type 2
      diabetic and non-diabetic control individuals of Mexican descent to test the working
      hypothesis that the community structure of the gut microbiome of individuals of Mexican
      descent with T2D is significantly altered compared to that of nondiabetics within the same
      population. To the investigators' knowledge, this multidisciplinary pilot study will be the
      first to investigate the gut microbial community structure of type 2 diabetic versus that of
      nondiabetic individuals of Mexican descent. Furthermore, it has the potential to provide
      mechanistic insight into how T2D predisposes individuals to the neuropathology and cognitive
      impairment characteristic of AD and to identify a novel class of interventions that target
      the host gut microbiome for the prevention of early onset AD in a predisposed population, as
      well as the population at large.

      Human subjects will be recruited through the University of Texas Medical Branch at Galveston
      (UTMB) Endocrinology and pre-screened to confirm that the potential participants meet
      established inclusion and exclusion criteria as either T2D or nondiabetic controls, as
      defined in the UTMB human subjects protocol associated with this project. Pre-screened
      participants that meet the defined criteria will be invited to attend an appointment with a
      study coordinator held at the UTMB Clinical Research Center. Consented and enrolled study
      participants will be asked to complete medical history, dietary preference, and
      gastrointestinal function questionnaires and instructed as to how to use the provided
      OMNIgene-GUT RNA (OMR)-200 fecal sample collection kit (DNA GenoTek). Participants will
      submit the collected fecal sample via shipment of a pre-paid and labeled shipping envelope.
      Samples will be deidentified and stored at -80oC in the Buffington Lab prior to shipment to
      the Baylor College of Medicine Center for Metagenomic and Microbiome Research (CMMR) for
      metagenomic 16S rRNA gene sequencing. Briefly, bacterial genomic DNA will be extracted using
      the MagAttract PowerSoil Kit (Qiagen) and the 16S ribosomal DNA (rDNA) V4 region will be
      amplified by polymerase chain reaction (PCR) and sequenced on the MiSeq platform (Illumina).
      16S rRNA gene read pairs will be demultiplexed based on unique molecular barcodes added to
      primers used for amplification and reads will be merged using USEARCH. 16S rRNA gene
      sequences will be clustered into Operational Taxonomic Units (OTUs) using the UPARSE
      algorithm and mapped to an optimized version of the SILVA database to determine taxonomies.
      The investigators will then use a custom script developed by the CMMR to construct a rarefied
      OTU table for downstream analyses of alpha-diversity, beta-diversity, and phylogenetic trends
      to identify any changes in community structure between type 2 diabetic and non-diabetic
      individuals of Mexican descent enrolled in the study.
    

Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        We will study subjects of Mexican descent living in Texas (aged 50-70 years) with a history
        of type 2 diabetes (T2D) (n=50, anticipated) and non-diabetic controls (aged 50 - 70 years)
        (n=50, anticipated).
      
Biospecimen description: 
      Fecal bacterial DNA specimens will be retained.