Liraglutide-induced structural modulation of the gut microbiota in patients with type 2 diabetes mellitus

Abstract

Accumulating evidence has suggested the importance of gut microbiota in the development of type 2 diabetes mellitus (T2DM). In the present study, 40 patients with T2DM were treated with liraglutide for 4 months. Feces samples and clinical characteristics were collected from these 40 T2DM patients before and after the liraglutide treatment. The diversity and composition of gut microbiota in the two groups were determined by sequencing the V4 region of bacterial 16S rRNA genes. Meanwhile, blood glucose, insulin, hemoglobin A1c (HbA1c), and lipid metabolism were also measured in the pre- and post-liraglutide-treatment groups. We find that Baseline HbA1c was associated with liraglutide treatment response (R2 = 0.527, β = − 0.726, p < 0.0001). After adjusted for baseline HbA1c, blood urea nitrogen was associated with liraglutide treatment response. Besides, our results showed reduced gut microbial alpha diversity, different community structure distribution and altered microbial interaction network in patients treated with liraglutide. The liner discriminant analysis (LDA) effect size (LEfSe) analysis showed that 21 species of bacteria were abundant in the pre-liraglutide-treatment group and 15 species were abundant in the post-liraglutide-treatment group. In addition, we also find that Megamonas were significantly correlated with older age, diabetes duration and diabetic retinopathy, Clostridum were significantly correlated with family history of diabetes and Oscillospira were significantly correlated with both diabetic retinopathy and diabetic peripheral neuropathy. Functional analysis based on Kyoto Encyclopedia of Genes and Genomes (KEGG) and cluster of orthologous groups (COG) annotations enriched three KEGG metabolic pathways and six functional COG categories in the post-liraglutide-treatment group. In conclusion, our research suggests that baseline HbA1c, blood urea nitrogen and gut microbiota are associated with the liraglutide treatment applied on patients with T2DM. These findings may contribute to the beneficial effects of liraglutide against diabetes.

Recent Insights into the Role of Gut Microbiota in Diabetic Retinopathy

“… 88 Liraglutide, which was approved by the FDA, in the application of T2DM was found to be associated with the reduction of gut microbial alpha diversity and the alteration of community distribution and the microbial interaction network. 89 Meanwhile, another GLP-1 analog, exendin-4 (Ex-4), can reduce BRB permeability, and modulate the inflammatory response to LPS as well as inhibit NF-κB activation. 90 Recently, it has been shown that GLP-1 intervention reduces the levels of NADPH oxidase 3 (NOX3), superoxide dismutase 2 (SOD2), caspase3 and light chain 3B (LC3B), while it activates the expression of B-cell lymphoma 2 (Bcl-2) in retina of type 2 diabetic rats, which suggests that GLP-1 treatment can alleviate apoptosis and autophagy of retinal cells.…”

Gut microbiota as a target for prevention and treatment of type 2 diabetes: Mechanisms and dietary natural products

“…Similarly, the same effect and mechanisms have been documented and confirmed in vivo [ 33 ]. Moreover, numerous studies have demonstrated that exogenous GLP-1 and PYY acutely reduce food intake in humans, which has been widely used in the treatment of T2DM[ 34 - 38 ]. Therefore, SCFAs not only contribute 5%-10% of energy to the host, but are also recognized by endogenous ligands of GPR41/43, and act as signaling molecules to participate in adjustment of energy[ 39 - 41 ].…”

Gut Microbial Signatures for Glycemic Responses of GLP-1 Receptor Agonists in Type 2 Diabetic Patients: A Pilot Study

“…As GLP-1 resistance is relatively common and gut microbiota composition varies widely among populations ( 18 ), perhaps specific gut microbial signatures determine responses to GLP-1 RA treatment. However, there are insufficient data to access relationships between gut microbiota composition and GLP-1 RA treatment efficacy ( 19 , 20 ). Therefore, in the pilot study, we analyzed gut microbiota of T2D patients treated with GLP-1 RA and determined clinical implications of gut microbiota in patients with distinct responses.…”