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

Junjie Shang; Fang Liu; Bing Zhang; Kunlun Dong; Man Lu; Rongfeng Jiang; Yue Xu; Le Diao; Jiangman Zhao; Hui Tang

doi:10.7717/peerj.11128

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

PeerJ. 2021 Apr 1:9:e11128. doi: 10.7717/peerj.11128. eCollection 2021.

Authors

Junjie Shang^#¹, Fang Liu^#², Bing Zhang¹, Kunlun Dong¹, Man Lu^{3

4}, Rongfeng Jiang^{3

4}, Yue Xu^{3

4}, Le Diao^{3

4}, Jiangman Zhao^{3

4}, Hui Tang^{3

4}

Affiliations

¹ Nanyang Second General Hospital, Nanyang, Henan Province, China.
² Kaifeng Central Hospital, Kaifeng, Henan Province, China.
³ Shanghai Biotecan Pharmaceuticals Co., Ltd., Shanghai, China.
⁴ Shanghai Zhangjiang Institute of Medical Innovation, Shanghai, China.

^# Contributed equally.

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 (R ₂ = 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.

Keywords: 16S rRNA gene sequencing; Gut microbiota; HbA1c; Liraglutide; Type 2 diabetes mellitus.

Grants and funding

This work was supported by the Key Technologies R & D Project of Nanyang Science and Technology Bureau (Henan Provincial Medical Science and Technique Program, 2018020989- KJGG2018101). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.