Effects of metformin, saxagliptin and repaglinide on gut microbiota in high-fat diet/streptozocin-induced type 2 diabetic mice

IF 3.7 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM BMJ Open Diabetes Research & Care Pub Date : 2024-05-01 DOI:10.1136/bmjdrc-2023-003837
Yangchen Tang, Mengli Yan, Zemin Fang, Song Jin, Tingjuan Xu
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Abstract

Introduction There has been increasing evidence that the gut microbiota is closely related to type 2 diabetes (T2D). Metformin (Met) is often used in combination with saxagliptin (Sax) and repaglinide (Rep) for the treatment of T2D. However, little is known about the effects of these combination agents on gut microbiota in T2D. Research design and methods A T2D mouse model induced by a high-fat diet (HFD) and streptozotocin (STZ) was employed. The T2D mice were randomly divided into six groups, including sham, Met, Sax, Rep, Met+Sax and Met+Rep, for 4 weeks. Fasting blood glucose level, serum biochemical index, H&E staining of liver, Oil red O staining of liver and microbiota analysis by 16s sequencing were used to access the microbiota in the fecal samples. Results These antidiabetics effectively prevented the development of HFD/STZ-induced high blood glucose, and the combination treatment had a better effect in inhibiting lipid accumulation. All these dosing regimens restored the decreasing ratio of the phylum Bacteroidetes: Firmicutes, and increasing abundance of phylum Desulfobacterota, expect for Met. At the genus level, the antidiabetics restored the decreasing abundance of Muribaculaceae in T2D mice, but when Met was combined with Rep or Sax, the abundance of Muribaculaceae was decreased. The combined treatment could restore the reduced abundance of Prevotellaceae\_UCG-001, while Met monotherapy had no such effect. In addition, the reduced Lachnospiraceae\_NK4A136_group was well restored in the combination treatment groups, and the effect was much greater than that in the corresponding monotherapy group. Therefore, these dosing regimens exerted different effects on the composition of gut microbiota, which might be associated with the effect on T2D. Conclusions Supplementation with specific probiotics may further improve the hypoglycemic effects of antidiabetics and be helpful for the development of new therapeutic drugs for T2D. Data are available upon reasonable request.
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二甲双胍、沙格列汀和瑞格列奈对高脂饮食/链脲佐菌素诱导的 2 型糖尿病小鼠肠道微生物群的影响
导言:越来越多的证据表明,肠道微生物群与 2 型糖尿病(T2D)密切相关。二甲双胍(Met)通常与沙格列汀(Sax)和瑞格列奈(Rep)联合用于治疗 T2D。然而,人们对这些联合用药对 T2D 患者肠道微生物群的影响知之甚少。研究设计和方法 采用高脂饮食(HFD)和链脲佐菌素(STZ)诱导的 T2D 小鼠模型。将 T2D 小鼠随机分为 6 组,包括假组、Met 组、Sax 组、Rep 组、Met+Sax 组和 Met+Rep 组,每组 4 周。采用空腹血糖水平、血清生化指标、肝脏 H&E 染色、肝脏油红 O 染色和微生物群 16s 测序分析来检测粪便样本中的微生物群。结果 这些抗糖尿病药物有效地防止了HFD/STZ诱导的高血糖的发生,联合治疗在抑制脂质积累方面效果更好。所有这些给药方案都恢复了类杆菌门和真菌门的比例下降趋势:除 Met 外,所有这些用药方案都恢复了类杆菌门与固有菌门比例的下降,以及脱硫菌门丰度的上升。在属的层面上,抗糖尿病药物恢复了 T2D 小鼠中 Muribaculaceae 丰度的下降,但当 Met 与 Rep 或 Sax 合用时,Muribaculaceae 的丰度下降。联合治疗可以恢复前胡科(Prevotellaceae/_UCG-001)减少的丰度,而 Met 单药治疗则没有这种效果。此外,联合治疗组中减少的 Lachnospiraceae\_NK4A136_group 也得到了很好的恢复,其效果远远大于相应的单药治疗组。因此,这些给药方案对肠道微生物群的组成产生了不同的影响,这可能与对 T2D 的影响有关。结论 补充特定益生菌可进一步改善抗糖尿病药物的降糖效果,有助于开发治疗 T2D 的新药。如有合理要求,可提供相关数据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
BMJ Open Diabetes Research & Care
BMJ Open Diabetes Research & Care Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
9.30
自引率
2.40%
发文量
123
审稿时长
18 weeks
期刊介绍: BMJ Open Diabetes Research & Care is an open access journal committed to publishing high-quality, basic and clinical research articles regarding type 1 and type 2 diabetes, and associated complications. Only original content will be accepted, and submissions are subject to rigorous peer review to ensure the publication of high-quality — and evidence-based — original research articles.
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