Effects of Metformin and Liraglutide on Gut Microbiota Composition in Youth-onset Type 2 Diabetes: The MIGHTY Study

Authors

• SB Glaros
• SL Cantor
• NA Macheret
• IN Kacker
• L Mabundo
• N Malandrino
• ST Chung

Abstract

Introduction: In Youth-onset Type 2 Diabetes (Y-T2D), Metformin (Met) and Liraglutide (Lira) are anti-diabetic therapies whose mechanisms of action may be mediated by altering the gut microbial composition. However, the effects of Met and Lira on short-chain fatty acid (SCFA) producing gut bacteria have been inconsistent in adults and there is no data on Y-T2D.
Objectives: To compare the composition and distribution of gut microbiota before and after 3 months of Met+Lira and Met.
Methods: Stool samples were characterized using whole-genome shotgun sequencing on Ilumina HiSeq 1000 Platform. Metagenomic Phylogenetic Analysis was used for taxonomic profiling of microbes and their relative abundance. The R packages “ggplot2” and “vegan” were employed to evaluate the community-based association by beta diversity. Alpha diversity determined species richness and evenness between the microbial profiles. Paired t-tests compared outcomes pre- to post-intervention.
Results: At baseline, 22 AA Y-T2D (15.3±2.1y, mean±SD, 68% female, BMI 40.1±7.9kg/m2) received Met+Lira (n=9) and Met (n=13). Met+Lira had higher HbA1c at baseline, and greater reductions in HbA1c (-1.2±0.8 vs. -0.3±0.6%, P <0.01). Microbial signature varied between the two groups at baseline, P <0.01. Compared to baseline, Met significantly (P<0.05) increased the abundance of SCFA-producing species: Eubacterium rectale, Bifidobacterium adolescentis, and Bifidobacterium longum, while Met+Lira increased the abundance of SCFA-producing species Anaerostipes hadrus and Bacteroides fragilis.
Conclusions: Short-term therapy of Met and Met+Lira in Y-T2D induced distinct shifts towards SCFA-producing gut microbiota. Ongoing functional analyses will explore the relationship of gut microbial shifts with glycemia.

Scientific Focus Area: Clinical Research

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