Effects of Probiotics on T2D MKR Mice Gut Microbiome

Objectives: The gastrointestinal tract harbors a diverse ecosystem of microbes that carry out a critical role in health and disease. In fact, bacterial cells outnumber human cells by 10:1. Recent studies have shown that microbial dysbiosis can lead to an increase in harmful metabolites that may alter systemic pathways including but not limited to insulin resistance. Consequently, the gut microbiome plays an important role in T2DM metabolic disorder and presents a potential target for bio-therapeutic treatments. We hypothesized that depletion of the gut microbiota via antibiotics and subsequent repopulation using commercially available probiotics would modulate intestinal gene expression.
Methods: Using both a hyperinsulinemic homozygous transgenic dominant-negative insulin like growth factor 1 receptor (MKR) mouse model and Wild Type (WT) model, eleven animals were divided into three cohorts: 1) WT control animals (n=3), 2) MKR_S (n=4), and 3) MKR_P (n=4). Shifts in the gut microbiome were analyzed via DNA extraction from fecal samples, PCR 16S rRNA amplification of V3-V4 hypervariable region, DNA analysis of 16S rRNA gene via Illumina MiSeq generated sequence data, and finally data analysis by QIMME 1.9.1 and R. Glucose monitoring was performed using blood samples collected from the tail tip via Bayer Contour blood glucose monitor system.
Results: Sequencing data suggests significant differences at the genus level between MKR and Wild Type mice. There were significant differences in the phylum Defferribacteres, Proteobacteria, TM7, Tenericutes and Verrucomicrobia between MKR and WT. Glucose level at baseline was consistent between MKR cohorts, however after challenge with either probiotic consortium (POC518) or probiotics from MKR fecal transfer, the MKR_Pro group was able to maintain the glucose level of healthy WT control (non—diabetic) while MKR_Sham levels remained consistent with baseline measures.
Conclusions: Altering the gut microbiome can lead to improved glucose tolerance. Future understanding of the specific species and mechanisms involved in the role of the gut microbiome on diabetes can provide new aspects regarding its pathophysiological relevance and pave the way for new therapeutic approaches.