Microbial Signatures Mapping of High and Normal Blood Glucose Participants in the Generation 100 Study

Intestinal dysbiosis has been linked to metabolic disorders, including insulin resistance and type 2 diabetes mellitus (T2DM). T2DM typically follows a prediabetic stage, during which insulin resistance develops. During the early stages of T2DM, its development can be corrected, thus potentially preventing or delaying the onset of the disease. This secondary, exploratory, cross-sectional comparison study aimed to contrast the gut microbiome of individuals with elevated fasting blood glucose to that of individuals with glucose levels within the normal range. This study involved 65 older adults (ages 76-83 years) enrolled from the randomized controlled trial entitled the "Generation 100 Study", all of whom consented to provide their gut microbiome samples. We employed a high-throughput sequencing of the bacterial 16S rRNA gene to obtain metagenomic microbial profiles for all participants. These profiles were then correlated with clinical measures. Overall, microbial alpha diversity was significantly reduced in the high glucose group. We have also observed distinct patterns of microbial beta diversity between high and normal glucose groups. At the phylum level, we found that Synergistes, Elusimicobia, Euryarchaeota, Verrucomicrobia, and Proteobacteria were all significantly decreased in participants with high blood glucose. Additionally, <i>P. copri</i> (ASV 909561) was significantly elevated (10-fold increase) in the high glucose groups, suggesting that it may serve as an early T2DM marker. In contrast to prior reports on the <i>Fusobacterium</i> genus, we found that it was significantly increased in the normal glucose group, with a significant 151-fold increase compared to the high glucose group. Directly linking gut microbiota profiles with clinical indicators such as fasting blood glucose and T2DM diagnosis allows the identification of specific microbial features associated with glucose dysregulation, providing preliminary population-level evidence to guide future translational research. Our results indicate significant changes in the microbiome that may provide valuable insights for early intervention in pre-diabetic states.