Association of Gut Microbiome with Diabetes Mellitus and Alzheimer’s Disease in a Puerto Rican Adult Population: A Preliminary Report

Abstract

AbstractBackgroundAlzheimer’s disease (AD) is the most common cause of dementia, consisting in a highly debilitating disorder, progressing from slight memory impairments to a complete loss of mental function, resulting in significant disability and death. In Puerto Rico, AD is the fourth leading cause of death. Caribbean Hispanics, including Puerto Ricans living on the island have shown a more severe AD symptomatology and disease mortality than any other ethnic group. This disparity may be due to health, diet, lifestyle, socioeconomic risk factors and more prevalent chronic health conditions such as diabetes in Hispanic people. Diabetes Mellitus is nowadays considered a risk factor for AD. Evidence suggests that the gut microbiome plays a role in the pathophysiology of AD through neuroinflammation and amyloid deposition leading to cognitive impairment. Main objective: Study the microbiome composition and diversity of Puerto Ricans with AD compared to cognitive‐intact controls in association with Diabetes Mellitus.MethodFifty‐three participants (n = 53), 28 with AD and 25 controls were evaluated clinically and cognitively with the Montreal Cognitive Assessment (MoCA) to associate the gut microbiome with cognitive impairment. Stool was collected for genomic DNA extractions and microbiome characterization. NextGen Illumina MiSeq was used to sequence 16S rRNA genes (V4 region) and analyzed with standard pipelines.ResultNo statistically significant differences in bacterial diversity and richness between AD vs. controls. We found slight differences in composition, including an abundance of Euryachaeota in AD, while controls had higher levels of Bacteroidetes. Compared to cognitively intact, a decrease in gut microbiome diversity was seen among participants with cognitive decline (p = 0.02). Roseburia (butyrate producing bacteria) seems to decrease with cognitive impairment severity. Diabetics have significantly reduced Anaerostipes and Ruminococcus also butyrate producing bacteria. AD participants with/without Diabetes have predominance of Euryarchaeota. Controls with Diabetes have more Proteobacteria and Bacteroidetes compared to cognitively impaired.ConclusionBoth Diabetes and neurocognitive decline appear to reduce butyrate‐producing bacterias, which may be related to a decrease in the homeostasis of the gut‐brain axis and lead to microbiome dysbiosis in the setting of disease. A better understanding of the gut microbiome will be an invaluable approach for development of modulation‐based therapeutic interventions.